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    • 专利摘要:
    The present invention relates to heterocyclylalkyl piperidine derivatives of formula I, enantiomers thereof, diastereomers thereof or mixtures thereof and / or syn or anti forms thereof, mixtures thereof or salts thereof, if necessary It is about: Formula I In the above formula, X 1 , X 2 , X 3 , X 4 and X 5 each represent> C—R ′ 1 to> C—R ′ 5 , or optionally only one of them represents N; R 2 is COOH, alkyloxycarbonyl, cycloalkyloxycarbonyl, CN, -CONRaRb or R 2 is CH 2 OH, substituted alkyl, or R 2 is -CF 2 -Rc, -C (CH 3 ) 2 -Rc, -CO-Rc, -CHOH-Rc, -C (cycloalkyl) -Rc or -CH = CH-Rc; R 3 is phenyl, heterocyclyl, alk-R o 3 ; Y is> CH-Re or difluoromethylene, carbonyl, hydroxyiminomethylene, alkyloxyiminomethylene, cycloalkyloxyiminomethylene radical or cycloalkylene-1,1 radical; n is 0 to 4, provided that the radical or phenyl or heterocyclyl moiety mentioned above may be optionally substituted.
    公开号:KR20030060934A
    申请号:KR10-2003-7006600
    申请日:2001-11-14
    公开日:2003-07-16
    发明作者:바께에릭；카리쟝-크리스또프；엘-아마드유세프；에베르미쉘；위베르필립；말레롱쟝-뤽；미냐니세르쥐；빵뗄귀；따바르미쉘；비비아니파브릭
    申请人:아방티 파르마 소시에테 아노님；
    IPC主号:
    专利说明:

    Heterocyclylalkyl piperidine derivatives, their preparation and compositions containing same
    [4] WO 99/37635 and WO 00/43383 describe antibacterial quinolylpropylpiperidine derivatives of the formula:
    [5] or
    [6] In the above formula,
    [7] The radicals R 1 are in particular (C1-6) alkoxy, R 2 is hydrogen, R 3 is located at 2 or 3 and is thiol, halogen, alkylthio, trifluoromethyl, carboxyl, alkyloxycarbonyl, alkylcarbonyl, Alkenyloxycarbonyl, alkenylcarbonyl, hydroxyl (optionally substituted by alky) and the like, (C1-6) alkyl, wherein R 4 represents a group -CH 2 -R 5 , wherein R 5 is selected from alkyl, hydroxyalkyl, alkenyl, alkynyl, tetrahydrofuryl, optionally substituted phenylalkyl, optionally substituted phenylalkenyl, optionally substituted heteroarylalkyl, optionally substituted heteroaryl, etc.) n is 0 to 2, m is 1 or 2, and A and B are especially hydrogen, sulfur, sulfinyl, sulfonyl, NR 11 , CR 6 R 7 , where R 6 and R 7 are H, thiol, alkyl Thio, halo, trifluoromethyl, alkenyl, alkenylcarbonyl, hydroxyl, amino), Z 1 and Z 2 are N or CR 1a and the like. These products exhibit antimicrobial activity. However, to date, disubstituted derivatives at the 4 position of piperidine have not been synthesized and consequently no biological activity has been found for any of those products.
    [8] It is not clear that the disubstituted derivatives at the 4 position of piperidine also exhibit antimicrobial activity, as some modification of the known structures can cause large activity changes.
    [9] EP 30044 describes quinoline derivatives useful as cardiovascular agents of the formula:
    [10]
    [11] In the above formula,
    [12] R 1 is especially alkyloxy, AB is —CH 2 —CH 2 —, —CHOH—CH 2 —, —CH 2 —CHOH—, —CH 2 —CO— or —CO—CH 2 —, and R 1 is H, OH or alkyloxy, R 2 is ethyl or vinyl, R 3 is especially alkyl, hydroxyalkyl, cycloalkyl, hydroxyl, alkenyl, alkynyl, tetrahydrofuryl, phenylalkyl, optionally substituted diphenyl Alkyl, optionally substituted phenylalkenyl, optionally substituted benzoyl or benzoylalkyl, optionally substituted heteroaryl or heteroarylalkyl, Z is H or alkyl or together with R 3 forms a cycloalkyl radical.
    [13] According to the present invention X 1 , X 2 , X 3 , X 4 and X 5 each represent> C—R ′ 1 to> C—R ′ 5 , or optionally only one of them represents a nitrogen atom,
    [14] R 1 , R ' 1 , R' 2 , R ' 3 , R' 4 and R ' 5 are the same or different and represent a hydrogen or halogen atom, or are alkyl, cycloalkyl, phenyl, phenylthio, mono- or bicy Click aromatic heterocyclyl or heterocyclylthio, hydroxyl, alkyloxy, trifluoromethoxy, alkylthio, trifluoromethylthio, cycloalkyloxy, cycloalkylthio, cyano, carboxyl, alkyloxycarbonyl, cyclo Alkyloxycarbonyl, -NRaRb or -CONRaRb radicals wherein Ra and Rb are hydrogen, alkyl, cycloalkyl, phenyl, mono- or bicyclic aromatic heterocyclyl or Ra and Rb together with the nitrogen atom to which they are attached May optionally contain other heteroatoms selected from O, S and N, and if necessary a nitrogen atom or, if necessary, a sulfur atom, wherein the sulfur atom is oxidized in the form of sulfinyl or sulfonyl To form a 5- or 6-membered heterocycle containing alkyl, phenyl or mono- or bicyclic aromatic heterocyclyl substituents; or fluoro, hydroxyl, alkyloxy, alkylthio, cycloalkyl To oxy, cycloalkylthio, phenyl, mono- or bicyclic aromatic heterocyclyl, carboxyl, alkyloxycarbonyl, cycloalkyloxycarbonyl, -NRaRb or -CONRaRb, where Ra and Rb are as defined above Methylene substituted by phenyl, phenoxy, heterocyclyloxy, benzyloxy, heterocyclylmethyloxy, or optionally R 1 is also difluoromethoxy or -C m F 2m + 1 , -SC m May represent a radical of F 2m + 1 or OC m F 2m + 1 , wherein m is an integer from 1 to 6, or optionally R ′ 5 may also represent trifluoroacetyl,
    [15] R 2 represents carboxyl, alkyloxycarbonyl, cycloalkoxycarbonyl, cyano, -CONRaRb, wherein Ra and Rb each represent hydrogen, alkyl, cycloalkyl, phenyl, mono- or bicyclic aromatic heterocyclyl , Ra or Rb represents hydroxyl, alkyloxy or cycloalkyloxy, or Ra and Rb together with the nitrogen atom to which they are attached may optionally contain other heteroatoms selected from O, S and N, 5-membered containing alkyl, phenyl or mono- or bicyclic aromatic heterocyclyl substituents at a nitrogen atom or, if necessary, a sulfur atom, wherein the sulfur atom is oxidized in the form of sulfinyl or sulfonyl; or Forms a six-membered heterocycle, or R 2 is hydroxymethyl, alkyl containing one or two carbon atoms substituted by carboxyl, alkyloxycarbonyl, Isloalkyloxycarbonyl, cyano or -CONRaRb, wherein Ra and Rb are as defined above, or R 2 is -CF 2 -Rc, -C (CH 3 ) 2 -Rc, -CO- Raccal of Rc, -CHOH-Rc, -C (cycloalkyl) -Rc or -CH = CH-Rc, wherein Rc is carboxyl, alkyloxycarbonyl, cycloalkyloxycarbonyl or -CONRaRb where Ra and Rb is as defined above),
    [16] R 3 is a phenyl, mono- or bicyclic aromatic heterocyclyl or alk-R O 3 radical, where alk is an alkyl radical and R o 3 is hydrogen, halogen, hydroxyl, alkyloxy, alkylthio, alkylsulphi Nyl, alkylsulfonyl, alkylamino, dialkylamino, cycloalkyl, cycloalkyloxy, cycloalkylthio, cycloalkylsulfinyl, cycloalkylsulfonyl, cycloalkylamino, N-cycloalkyl-N-alkylamino, -N -(Cycloalkyl) 2 , acyl, cycloalkylcarbonyl, phenyl, phenoxy, phenylthio, phenylsulfinyl, phenylsulfonyl, phenylamino, N-alkyl-N-phenylamino, N-cycloalkyl-N-phenyl Amino, -N- (phenyl) 2 , phenylalkyloxy, phenylacylthio, phenylalkylsulfinyl, phenylalkylsulfonyl, phenylalkylamino, N-alkyl-N-phenylaminoalkyl, N-cycloalkyl-N-phenyl Alkylamino, benzoyl, mono- or bicyclic aromatic heterocyclyl, he Rocyclyloxy, heterocyclylthio, heterocyclylsulfinyl, heterocyclylsulfonyl, heterocyclylamino, N-alkyl-N-heterocyclylamino, N-cycloalkyl-N-heterocyclylamino, hetero Cyclylcarbonyl, heterocyclylalkyloxy, heterocyclylalkylthio, heterocyclylalkylsulfinyl, heterocyclylalkylsulfonyl, heterocyclylalkylamino, N-alkyl-N-heterocyclylaminoalkyl, N -Cycloalkyl-N-heterocyclylaminoalkyl, wherein the heterocyclyl moiety mentioned above is mono- or bicyclic aromatic, carboxyl, alkyloxycarbonyl, -NRaRb or -CO-NRaRb, wherein Ra and Rb is as defined in the definition of R 2 ), or optionally R o 3 is -CR'b = CR'c-R'a, where R'a is phenyl, phenylalkyl, heterocyclyl or hetero Cyclylalkyl, where heterocyclyl moiety Minutes are mono- or bicyclic aromatic), phenoxyalkyl, phenylthioalkyl, phenylsulfinylalkyl, phenylsulfonylalkyl, phenylaminoalkyl, N-alkyl-N-phenylaminoalkyl, heterocyclyloxyalkyl, Heterocyclylthioalkyl, heterocyclylsulfinylalkyl, heterocyclylsulfonylalkyl, heterocyclylaminoalkyl, N-alkyl-N-heterocyclylaminoalkyl, heterocyclylthio, heterocyclylsulfinyl, heterocycle Arylsulfonyl (heterocyclyl moiety mentioned above is mono- or bicyclic aromatic), phenylthio, phenylsulfinyl, phenylsulfonyl, R'b and R'c represent hydrogen, alkyl or cycloalkyl Or optionally R o 3 represents a radical -C≡C-Rd wherein Rd is alkyl, phenyl, phenylalkyl, phenoxyalkyl, phenylthioalkyl, N-alkyl-N-phenylaminoalkyl, mono -Or bicyclic aromatic hete Cyclyl, heterocyclylalkyl, heterocyclyloxyalkyl, heterocyclylthioalkyl, heterocyclylaminoalkyl, N-alkyl-N-heterocyclylaminoalkyl (heterocyclyl moieties mentioned above are mono -Or bicyclic aromatic)], or optionally R o 3 represents -CF 2 -phenyl or mono- or bicyclic aromatic -CF 2 -heterocyclyl radical,
    [17] Y is a radical> CH-Re, wherein Re is hydrogen, fluoro, hydroxyl, alkyloxy, cycloalkyloxy, carboxyl, alkyloxycarbonyl, cycloalkyloxycarbonyl, -NRaRb or -CO-NRaRb [where Ra and Rb are as defined in the definition of R 2 , or one is a hydrogen atom and the other is an alkyloxycarbonyl, acyl, cycloalkylcarbonyl, benzoyl or heterocyclylcarbonyl radical, wherein the heterocyclyl moiety is Mono- or bicyclic aromatic), or optionally Y is difluoromethylene, carbonyl, hydroxyliminomethylene, alkyloxyiminomethylene or cycloalkyl containing from 3 to 6 carbon atoms. Oxyiminomethylene radical or 1,1-cycloalkylene radical,
    [18] n is an integer of 0 to 4,
    [19] The phenyl, benzyl, benzoyl or heterocyclyl radicals or moieties mentioned above may be optionally substituted with halogen, hydroxyl, alkyl, alkyloxy, alkyloxyalkyl, haloalkyl, trifluoromethyl, trifluoromethoxy, trifluoromethylthio Selected from carboxyl, alkyloxycarbonyl, cyano, alkylamino, -NRaRb, wherein Ra and Rb are as defined above, phenyl, hydroxyalkyl, alkylthioalkyl, alkylsulfinylalkyl and alkylsulfonylalkyl The products of formula (I), enantiomers, diastereomers or mixtures thereof and / or, if necessary, syn or anti forms thereof, mixtures thereof or salts thereof, which may be substituted by 1 to 4 substituents, are potent It has been found to be an antimicrobial agent, which forms an aspect of the present invention.
    [20] Alkyl or acyl radicals and moieties contain 1 to 10 carbon atoms in the straight or side chain (except where specifically noted) and cycloalkyl radicals contain 3 to 6 carbon atoms.
    [21] In addition, radicals representing or containing halogen atoms represent halogens selected from fluorine, chlorine, bromine and iodine, preferably fluorine.
    [22] Radicals in the above formulas represent or contain mono- or bicyclic aromatic heterocyclyl substituents, which substituents contain 5 to 10 chain members and may be optionally substituted by thienyl, Furyl, pyrrolyl, imidazolyl, thiazolyl, oxazolyl, thiadiazolyl, oxdiazolyl, tetrazolyl, pyridyl, pyridazinyl, pyrazinyl, pyrimidinyl, indolyl, benzothienyl, benzofuryl, Indazolyl, benzothiazolyl, naphthyridinyl, quinolyl, isoquinolyl, cinnoyl, quinazolyl, quinoxalyl, benzoxazolyl and benzimidazolyl.
    [1] The present invention relates to a heterocyclylalkyl piperidine derivative of the formula (I) which acts as an antimicrobial agent:
    [2]
    [3] The present invention also relates to a process for preparing the compound of formula (I) and to a composition containing the same.
    [23] According to the invention, the product of formula (I) is capable of coupling chain R 3 with the following heterocyclylalkyl piperidine derivatives of formula (II) and then optionally removing acid protecting or amine protecting radicals, optionally enantiomers or dia It can be obtained by separating the stereomeric form and / or, if necessary, by separating the syn or anti form and optionally converting the obtained product into a salt.
    [24]
    [25] In the above formula,
    [26] X 1 , X 2 , X 3 , X 4 , X 5 , R 1 , R 2 , Y and n are as defined above,
    [27] R 2 is protected when it contains a carboxyl or amino radical.
    [28] Coupling chain R 3 with piperidine is advantageously inert in an anhydrous medium, preferably in an organic solvent such as amide (e.g. dimethylformamide), ketone (e.g. acetone) or nitrile (e.g. acetonitrile). The derivative of Formula IIa, which acts in a medium (e.g. nitrogen or argon), is refluxed at 20 ° C. to solvent in the presence of a base such as an organic nitrogen base (e.g. triethylamine) or an inorganic base (alkaline carbonate such as potassium carbonate). This is done by acting at temperatures between temperatures. The nitrogen atom of the piperidine in the derivative of formula II is optionally protected according to useful methods that do not affect the rest of the molecule or the reaction. For example, the protection is carried out by a protecting radical selected from t-butoxycarbonyl and benzyloxycarbonyl. Preferably, the derivative of formula (IIa) wherein X is bromine or iodine atom.
    [29] R 3 -X
    [30] In the above formula,
    [31] R 3 is as defined above,
    [32] X represents a halogen atom, a methylsulfonyl radical, a trifluoromethylsulfonyl radical or a p-toluenesulfonyl radical.
    [33] If R 3 is a phenyl radical, see also J. Org. Chem., 6066 (1997) or Tet. Lett., 6359 (1997) can be operated in the iodo or bromo derivative R 3 -X in the presence of a palladium catalyst. The palladium catalyst is optionally selected from 18-C-6 (1,4,7,10,1) in the presence of a base such as sodium tert-butoxide or cesium carbonate in a solvent such as, for example, tetrahydrofuran, tetraglyme or toluene. Tris (dibenzylideneacetone) dipalladium and 2,2'-bis (diphenylphosphino) -1,1'-binaphthyl or 2 in the presence of a crown ether such as 13,16-hexaoxaoctaoctadecane) Palladium diacetate with a ligand such as-(di-t-butylphosphino) -biphenyl. The reaction is carried out at a temperature of 20 ° C to 110 ° C.
    [34] R 3 is a radical -alk-R o 3 where alk represents an alkyl radical and R o 3 represents -C = C-Rd where Rd is phenyl, phenylalkyl, heterocyclyl or mono- or bicyclic Aromatic heterocyclylalkyl), alkynyl halide: HC≡C-alk-X, where alk is as defined above and X is a halogen atom, followed by chain chain phenyl, phenyl Preference is given to substitution by alkyl, heterocyclyl or heterocyclylalkyl radicals.
    [35] In this alternative, the addition of the alkynyl chain is carried out in the presence or absence of an alkali metal iodide such as potassium iodide or sodium iodide: HC≡C-alk-X, where X is preferably a bromine atom. Is carried out under the conditions described above for bonding the chain R 3 .
    [36] Substitution with phenyl or heterocyclyl radicals is carried out in the presence of triethylamine in anhydrous medium in a solvent such as amide (eg dimethylformamide) or nitrile (eg acetonitrile) and for example tetrakis (triphenyl By the action of a halide derived from a cyclic radical to be substituted at a temperature between 20 ° C. and the reflux temperature of the solvent in the presence of a palladium salt such as phosphine) palladium and copper iodide.
    [37] Substitution with phenylalkyl or heterocyclylalkyl radicals is carried out in basic media, for example in the presence of potassium hydride or sodium hydride or n-butyllithium in a solvent such as ether (tetrahydrofuran) or amide (dimethylformamide). , By the action of the corresponding halide at a temperature between −60 ° C. and the boiling point of the reaction medium.
    [38] If the alkyl radical represented by R 3 has carboxyl or amino substituents, these substituents are protected beforehand and then released after the reaction. The process is a conventional method which does not affect the remainder of the molecule, especially in the literature [see: TWGreene and PGM Wuts, Protective Groups in Organic Synthesis (2 nd edition), A. Wiley - Interscience Publication (1991) or by McOmie, Protective Groups in Organic Chemistry, Plenum Press (1973).
    [39] The protected carboxyl radical included in R 2 may be selected from esters that are readily hydrolyzed. Examples that may be mentioned include methyl, benzyl and tert-butyl esters or phenyl propyl or allyl esters. The protection of the carboxyl radicals is optionally carried out simultaneously with the reaction.
    [40] If necessary, the amino radicals are protected using the usual protecting radicals mentioned in the literature.
    [41] These protecting radicals are added and removed according to the conventional methods mentioned above for R 3 .
    [42] R 3 is a radical-alk-R o 3 wherein alk is an alkyl radical and R o 3 is a phenoxy, phenylthio, phenylamino, heterocyclyloxy, heterocyclylthio or heterocyclylamino radical, wherein Heterocyclyl moiety is aromatic), firstly the chain HO-alk-X, wherein X is a halogen atom, preferably iodine, under the conditions as described above for the reaction of the product of formula IIa After condensation, the hydroxyalkyl chain is converted to a haloalkyl, methanesulfonylalkyl or p-toluenesulfonylalkyl chain and finally an aromatic derivative of Ar-ZH in the basic medium, wherein Ar is an aromatic phenyl or heterocyclyl Radical, and Z is a sulfur, oxygen or nitrogen atom).
    [43] The conversion of hydroxylated chains to haloalkyl or p-toluenesulfonyl chains is in accordance with conventional methods of halogenation or sulfonylation, in particular halogenating agents [e.g. thionyl chloride, halophosphorus derivatives (e.g. phosphorus). Trichloride or tribromide)] or sulfonylating agents such as methanesulfonyl chloride, p-toluenesulfonyl chloride or trifluoromethanesulfonic anhydride. This reaction is carried out at temperatures of 0 ° C. to 60 ° C. in organic solvents such as chlorinated solvents such as dichloromethane or chloroform. As a specific case, it may be advantageous to work in the presence of a base such as pyridine or triethylamine.
    [44] The reaction of the aromatic derivative Ar—ZH is advantageously between 20 ° C. and the reflux temperature of the reaction mixture in the presence of a base such as a nitrogenous organic base (eg triethylamine) or an inorganic base (alkali metal carbonate, eg potassium carbonate). As described above for the action of the derivative of formula (IIa) in the presence of a base such as a nitrogenous base in an organic solvent such as amide (eg dimethylformamide), ketone (eg acetone) or nitrile (eg acetonitrile) at temperature Do as follows. It may be advantageous to work in the presence of potassium iodide.
    [45] According to the invention, the heterocyclylalkyl piperidine derivatives of the formula (II) can be prepared according to the bonding method described below, starting from one of the derivatives of the formula (II) already obtained, if necessary, via the following methods ① through Conversion according to one of 9 can produce derivatives corresponding to Y and / or R 1 , R ' 1 , R' 2 , R ' 3 , R' 4 or R ' 5 .
    [46] If carboxylic acid radicals are present on the molecule, these radicals are liberated according to conventional methods, in particular the methods mentioned in the literature cited above, which preprotect and then do not affect the rest of the molecule after the reaction. It is also understood that in the derivatives of the formula (II), the amine is protected and then released after the reaction, which can block the amine of piperidine. The protection is carried out in particular according to the conventional methods described above, in particular via t-butoxycarbonyl or benzyloxycarbonyl radicals.
    [47] According to the invention, the preparation of the product of formula (II) wherein Re is a hydrogen atom in Y comprises combining a heterocyclic derivative of formula (III) with a piperidine derivative of formula (IV), followed by removal of protective radicals and / or accordingly The bicyclic substituent of the obtained heterocyclylalkyl piperidine derivative of formula (II) is converted via subsequent operation to contain the radicals R 1 , R ' 1 , R' 2 , R ' 3 , R' 4 or R ' 5 This is accomplished by generating one expected derivative and, if necessary, removing the protective radicals still present in the molecule:
    [48]
    [49]
    [50] In the above formula,
    [51] R 1 , X 1 , X 2 , X 3 , X 4 and X 5 are as defined above,
    [52] Hal represents a halogen atom,
    [53] Rz is a protective radical,
    [54] R ″ 2 represents a protected radical as defined above or when R 2 represents or contains a carboxylic acid functional group.
    [55] The radical Rz may be any protecting group for reaction compatible nitrogen atoms, for example t-butyloxycarbonyl or benzyloxycarbonyl. The protecting group for the acid functional group is selected from ordinary groups, in which the addition and removal thereof does not affect the rest of the molecule, in particular those mentioned in the above cited literature.
    [56] The reaction is described in Suzuki et al., Pure and Appl. Chem., 57 , 1749 (1985), according to a similar method of organoborane in a solvent such as ether (e.g. tetrahydrofuran or dioxane) at a temperature between -20 ° C and 20 ° C. 9-borabicyclo- [3.3.1] nonane) followed by the continuous action of bicyclic derivatives of formula III, wherein Hal is preferably a bromine or iodine atom or a chlorine atom. The reaction is generally carried out at a temperature between 20 ° C. and the reflux temperature of the solvent in the presence of a palladium salt (eg diphenylphosphinoferrocenepalladium chloride) and a base (eg potassium phosphate).
    [57] (1) Heterocyclylalkyl piperidine of formula (II) wherein Re in Y represents a hydroxyl radical can be prepared by oxidizing a corresponding heterocyclylalkyl piperidine derivative of formula (II) in which Re in Y is a hydrogen atom in a basic medium. have. The oxidation is preferably effected by the action of oxygen in an inert solvent such as dimethyl sulfoxide in the presence of tert-butanol and a base such as potassium tert-butoxide or sodium tert-butoxide at temperatures between 0 ° C. and 100 ° C. To be carried out.
    [58] A heterocyclylalkyl piperidine derivative in which Re in Y is a fluorine atom is prepared by fluorination starting with a derivative in which Re is hydroxyl. This reaction is carried out in the presence of sulfur fluoride [eg, aminosulfur trifluoride (diethylaminosulfur trifluoride (Tetrahedron, 44, 2875 (1988), bis (2-methoxyethyl) amino-sulfur trifluoride ( In the presence of Deoxofluor R ) or morpholinosulfur trifluoride) or alternatively in the presence of sulfur tetrafluoride (see J. Org. Chem., 40, 3808 (1975)). Silver can also be carried out using a fluorinating agent such as hexafluoropropyldiethylamine (JP 2 039546) or N- (2-chloro-1,1,2-trifluoroethyl) diethylamine. Silver is an organic solvent or ether (e.g., tetrahydrofuran or dioxane) such as a chlorinated solvent (e.g. dichloromethane, dichloroethane or chloroform) at a temperature of -78 ° C to 40 ° C (preferably 0 ° C to 30 ° C) ), Advantageously inert Medium, in particular working in an argon or nitrogen.
    [59] Heterocyclylalkyl piperidine of formula (II) wherein Re in Y is an alkyloxy or cycloalkyloxy radical is prepared by the action of an alkyl or cycloalkyl halide in the corresponding derivative of formula (II) wherein Re is hydroxyl. The reaction is generally carried out at temperatures between 20 ° C. and 100 ° C., N, N-dimethylformamide or dimethyl in the presence of an acid acceptor such as trialkylamine (eg triethylamine) or alkali metal halide (eg sodium hydride). It is carried out with bromide or chloride in an inert solvent such as sulfoxide.
    [60] Heterocyclylalkyl piperidine derivatives of formula II wherein Y is a carbonyl radical can be prepared by oxidizing the corresponding derivative of formula II wherein Re in Y is a hydroxyl radical. This oxidation can be effected, for example, by using potassium permanganate in a solution of sodium hydroxide (eg 3N sodium hydroxide), optionally at a temperature of -20 ° C to 20 ° C, or alternatively reacting oxalyl chloride in the presence of dimethyl sulfoxide In D. Swern et al., J. Org. Chem., 44, 4148 (1979), is carried out by the addition of an amine such as triethylamine in an inert solvent such as dichloromethane or dimethyl sulfoxide at a temperature of -60 ° C to 20 ° C.
    [61] Heterocyclylalkyl piperidine derivatives of formula (II), wherein Y is a difluoromethylene radical, can be prepared by dihalogenating the product of formula (II), wherein Y is carbonyl, under conditions similar to the method of fluorination described above.
    [62] Heterocyclylalkyl piperidine derivatives of formula (II) wherein Y is a hydroxyiminomethylene radical can be prepared by reacting hydroxylamine to a derivative of formula (II) wherein Y is a carbonyl radical. This reaction is generally carried out at temperatures between 0 ° C. and the boiling point of the reaction mixture, in an inert solvent such as alcohol (methanol or ethanol) and optionally in the presence of sodium hydroxide (eg 1N sodium hydroxide).
    [63] Heterocyclylalkyl piperidine derivatives of formula II wherein Y is an alkyloxyiminomethylene or cycloalkyloxyiminomethylene radical are prepared by the action of an alkyl or cycloalkyl halide to the corresponding derivative of formula II wherein Y is hydroxyliminomethylene. can do. This reaction is generally carried out at temperatures between 20 ° C. and 100 ° C., in the presence of acid acceptors such as trialkylamines (eg triethylamine) or alkali metal hydrides (eg sodium hydride), N, N-dimethylformamide Or in an inert solvent such as dimethyl sulfoxide. Preferably bromide is used.
    [64] Heterocyclylalkyl piperidine derivatives of formula (II) wherein Re in Y is a radical -NRaRb are amines HNRaRb () in an inert solvent such as N, N-dimethylformamide or dimethyl sulfoxide at temperatures between 20 ° C and Or, if necessary, ammonia when Re is -NH 2 ), to prepare from the corresponding tosyloxy derivatives. When ammonia is reacted, this process is preferably carried out at 2 to 20 at a temperature of 20 ° C to 100 ° C. Carry out under pressure of atmospheric pressure. If this process is carried out using amine HNRaRb, this reaction is optionally carried out in the presence of a base such as trialkylamine (eg triethylamine), pyridine or alkali metal hydride (eg sodium hydride). Derivatives in which Re in Y is tosyloxy are obtained by reacting tosyl chloride in pyridine at a temperature of −10 ° C. to 20 ° C. from a product of formula II wherein Re in Y is hydroxyl.
    [65] Heterocyclylalkyl piperidine derivatives of formula (II) wherein Re in Y is a carboxyl radical, provide alkaline cyanide to the corresponding tosyloxy derivatives, such as dimethylformamide or dimethylsulfoxide, at temperatures between 0 ° C. and the boiling point of the reaction mixture. The nitrile obtained by acting in an organic solvent or an aqueous-organic medium, for example a water-alcohol mixture, and then reacting a strong acid such as hydrochloric acid and optionally a lower aliphatic alcohol at a temperature between 0 ° C. and the boiling point of the reaction mixture, is hydrolyzed. Can be prepared. Preference is given to using sodium cyanide or potassium cyanide.
    [66] Heterocyclylalkyl piperidine derivatives of formula II wherein Re in Y is alkyloxycarbonyl or cycloalkyloxycarbonyl or -CO-NRaRb are alcohols or corresponding amines to derivatives of formula II wherein Re in Y is a carboxyl radical, respectively. Can be prepared by working. The reaction is carried out at temperatures between 0 ° C. and the reflux temperature of the reaction mixture, ethers (eg tetrahydrofuran or dioxane), amides (N, N-dimethylformamide), chlorinated solvents (eg methylene chloride, 1,2). In an inert solvent such as dichloroethane or chloroform) or dimethyl sulfoxide, in the presence of a binder such as carbodiimide (eg, N, N'-dicyclohexylcarbodiimide) or N, N'-carbonyldiimidazole Conduct.
    [67] Heterocyclylalkyl piperidine derivatives of formula II wherein Y is a 1,1-cycloalkylene radical are cycloalkyls in which Alk is expected in heterocyclylalkyl piperidine derivatives in which Re in Y is a hydrogen atom in a basic medium. It can be prepared by reacting the product of Hal-Alk-Hal, the alkylene radical corresponding to lene. The reaction is generally carried out in an inert solvent such as N, N-dimethylformamide or dimethyl sulfoxide in the presence of an acid acceptor such as an alkali metal hydride (e.g. sodium hydride) at a temperature between 20 ° C and 100 ° C. .
    [68] ③ heterocycle of formula II wherein one of R 1 , R ' 1 , R' 2 , R ' 3 , R' 4 and R ' 5 is an alkyl, cycloalkyl, phenyl, heterocyclyl, benzyl or heterocyclylmethyl radical The arylalkyl piperidine derivatives include those of R'iB (OH) 2 , wherein R ' i is substituent R 1 , R' 1 , R ' 2 , in which derivative R' i is a bromine, iodine or chlorine atom. A boron derivative of R ' 3 , R' 4 or R ' 5 ) or 9-alkyl- (or 9-cycloalkyl) -9-borabicyclo [3.3.1] nonane, from 20 ° C. to reaction At temperatures between the reflux temperatures of the mixture, in the presence of a base such as a palladium salt (e.g. tetrakis (triphenyl-phosphine) or diphenylphosphinoferrocene-palladium chloride) and potassium phosphate, an amide (e.g. N, N In an inert solvent such as -dimethylformamide), ether (e.g. tetrahydrofuran) or nitrile (e.g. acetonitrile), see F. Diederic h and PJ Stang, Metal Catalysed Cross-coupling Reactions, Wiley-VCH, (1997).
    [69] ( 4) Heterocyclylalkyl piperidine derivatives of formula (II) wherein one of R 1 , R ' 1 , R' 2 , R ' 3 , R' 4 and R ' 5 represents a radical -NRaRb is a derivative of formula II and In the presence of a palladium catalyst, under conditions similar to those described for reacting the halo derivatives of J. Org. Chem. 6066 (1997) and Tetrahedron Lett., 6359 (1997), in a manner similar to the substituent R ' 1 (R' i is a substituent R 1 , R ' 1 , R' 2 , R ' 3 , R' 4 or R ′ 5 ) may be prepared by reacting the amine HNRaRb with a derivative of formula II wherein bromine, iodine or a chlorine atom.
    [70] When Ra and Rb represent hydrogen atoms, the obtained amino derivatives are alkaline nitrites (e.g., tetrafluoroboric acid or hexafluorophosphoric acid) in water at temperatures between -10 ° C and 20 ° C. Sodium nitrite) to produce diazonium tetrafluoroborate or hexafluorophosphate, and the product obtained is described in Org. Synth., Coll 5, 133 (1973)] can be converted to fluoro derivatives by pyrolysis following the Baz-Schieman reaction.
    [71] ⑤ R 1 , R ' 1 , R' 2 , R ' 3 , R' 4 or R ' 5 represent an alkyloxy, alkylthio, cycloalkyloxy, cycloalkylthio, benzyloxy or heterocyclylmethyloxy radical Heterocyclylalkyl piperidine derivatives of II can be prepared by reacting an alcohol or the corresponding thiol to a heterocyclylalkyl piperidine derivative wherein one of the radicals R ′ 1 is bromine, iodine or chlorine atom. This reaction is generally at the reflux temperature of the reaction mixture from 0 ° C. to the presence of an acid acceptor such as trialkylamine (eg triethylamine), alkali metal hydride (eg sodium hydride), methyllithium or n-butyllithium Under an inert solvent such as ether (eg tetrahydrofuran or dioxane), amide (eg N, N-dimethylformamide) or dimethyl sulfoxide.
    [72] Heterocyclylalkyl piperidine derivatives of formula (II) wherein R 1 , R ' 1 , R' 2 , R ' 3 , R' 4, or R ' 5 represent hydroxyl radicals, wherein one of the radicals R' i is methoxy From the corresponding derivatives, they can be prepared by reacting a strong acid, such as hydrobromic acid, at a temperature between 20 ° C. and the reflux temperature of the reaction mixture.
    [73] Heterocyclylalkyl piperidine derivatives of formula (II) in which R 1 , R ' 1 , R' 2 , R ' 3 , R' 4 or R ' 5 represent a trifluoromethoxy radical start the corresponding hydroxyl derivative As a substance, it can be obtained by a method similar to that described in Sun WY Synlett., 11 , 1279 (1997). This radical is described in Kuorboshi M. et al., Tetrahedron Lett in the presence of 1,3-dibromo-5,5-dimethylhydantoin in HF-pyridine complex at temperatures between 0 ° C and 20 ° C. , 33 (29), 4173 (1992) is applied to convert to trifluoromethyl radicals.
    [74] Formula wherein R 1 , R ' 1 , R' 2 , R ' 3 , R' 4 or R ' 5 represent an alkyloxy, cycloalkyloxy, phenoxy, benzyloxy, heterocyclyloxy or heterocyclylmethyloxy radical Heterocyclylalkyl piperidine derivatives of II can be obtained by reacting a halo derivative corresponding to a derivative of formula II wherein R ' i to be modified is hydroxyl. This process is preferably carried out at temperatures between 0 ° C. and the reflux temperature of the reaction mixture, see J. Am. Chem. Soc., 4369 (1999); Tetrahedron Lett., 8005 (1997); Angew. Chem. Int. Ed. Engl., 2047 (1998), in a manner similar to the method described in the above, optionally in the presence of a palladium salt, trialkylamines (eg triethylamine), alkali metal hydrides (eg sodium hydride), methyllithium or N-butyl In the presence of an acid acceptor such as lithium, using bromo derivatives in an inert solvent such as ether (e.g. tetrahydrofuran or dioxane), amide (e.g. N, N-dimethylformamide) or dimethyl sulfoxide .
    [75] (6) Heterocyclylalkyl piperidine derivatives of formula (II) in which R 1 represents a trifluoromethyl radical are described in JCS Chem. Commun., 1, 53 (1992) or Chem. Commun., 18, 1389 (1993), at a temperature of 20 ° C. to 150 ° C., in a solvent such as dimethylformamide, in the presence of a copper or cuprous salt, such as CuI, radicals R 1 It can be prepared by the action of a trifluoromethylating agent (particularly bromo derivative Br-CF 3 or iodo derivative I-CF 3 ) to a heterocyclylalkyl piperidine derivative wherein one is bromine, iodine or chlorine atom. .
    [76] ⑦ of Formula II wherein R 1 , R ′ 1 , R ' 2 , R' 3 , R ' 4 or R' 5 represent an alkylthio, cycloalkylthio, trifluoromethylthio, phenylthio or heterocyclylthio radical Heterocyclylalkyl piperidine derivatives can be obtained by acting a halo derivative corresponding to a heterocyclylalkyl piperidine derivative with a mercapto substituent. This process is preferably carried out using a bromo derivative, under the above-mentioned conditions for the action of the halo derivative on the alcohol, at temperatures between 20 ° C. and the reflux temperature of the reaction mixture. In the case of trifluoromethylthio radicals, this process is described in Tet. Lett., 33 (44), 6677 (1992).
    [77] Mercapto derivatives of heterocyclylalkyl piperidine of formula (II) are described in QL Zhou et al., Tetrahedron, 15 , 4467 (1994); C. Bieniauz et al., Tetrahedron Letters, 34 , 6, 939 (1993) and ED Amstuts, J. Am. Chem. Soc., 68 , 498 (1946), obtained from heterocyclylalkyl piperidine derivatives in which one of the radicals R ' i is a bromine, iodine or chlorine atom (preferably bromine atom) can do. This reaction is carried out, for example, at a temperature between 20 ° C. and the reflux temperature of the reaction mixture, optionally in the presence of water, in the presence of Na 3 PO 3 S or Na 2 S in an inert solvent such as alcohol (eg methanol or ethanol). Under the following conditions.
    [78] (8) Heterocyclylalkyl piperidine derivatives of formula (II) wherein R 1 , R ' 1 , R' 2 , R ' 3 , R' 4 or R ' 5 represent a cyano radical, wherein one of the radicals R' i is a halogen atom , From the corresponding derivatives, preferably bromine or iodine atoms, in the presence of CuCN or KCN, optionally in the presence of a catalyst, see Halley F. et al., Synth. Comm., 27, 7, 1199 (1997) and Tschaen DM et al., J. Org. Chem., 60, 14, 4324 (1995).
    [79] Heterocyclylalkyl of Formula II wherein R 1 , R ' 1 , R' 2 , R ' 3 , R' 4 or R ' 5 represent a carboxyl, alkyloxycarbonyl, cycloalkyloxycarbonyl or -CO-NRaRb radical Piperidine derivatives can be prepared from cyano derivatives according to conventional methods for conversion to acids, esters and amides and some of the reaction conditions described above, which do not affect the rest of the molecule. In particular, at temperatures between 0 ° C. and the reflux temperature of the reaction mixture, ethers (tetrahydrofuran or dioxane), amides (N, N-dimethylformamide) or chlorinated solvents (methylene chloride, 1,2-dichloroethane or chloroform ), In the presence of carbodiimide (N, N'-dicyclohexylcarbodiimide) or N, N'-carbonyldiimidazole.
    [80] (9) Heterocyclylalkyl piperidine derivatives of formula (II) wherein R 1 , R ' 1 , R' 2 , R ' 3 , R' 4 or R ' 5 represent a hydroxymethyl radical, wherein one of the radicals R' i is a carboxyl Heterocyclylalkyl piperidine derivatives of the formula (II), which represent radicals, may be used at temperatures between 0 ° C. and the reflux temperature of the reaction mixture, ethers (eg tetrahydrofuran or dioxane), amides (eg N, N-dimethyl In an inert solvent such as formamide) or a chlorinated solvent such as methylene chloride, 1,2-dichloroethane or chloroform, it can be obtained by reduction using a reducing agent such as lithium aluminum hydride or borohydride.
    [81] Heterocyclylalkyl piperidine derivatives of formula (II) wherein R 1 , R ' 1 , R' 2 , R ' 3 , R' 4 or R ' 5 represent alkyloxymethyl or cycloalkyloxymethylradicals are radicals R' i It can be obtained by the action of a corresponding halo derivative (preferably bromo derivative) to the corresponding heterocyclylalkyl piperidine derivative, which represents a hydroxymethyl radical. The reaction is generally carried out at temperatures between 20 ° C. and 100 ° C., in the presence of an acid acceptor such as trialkylamine (eg triethylamine) or alkali metal hydride (eg sodium hydride), ether (eg tetrahydro). In an inert solvent such as furan or dioxane), amide (eg N, N-dimethylformamide) or dimethyl sulfoxide.
    [82] Heterocyclylalkyl piperidine derivatives of formula (II) in which R 1 , R ' 1 , R' 2 , R ' 3 , R' 4 or R ' 5 represent fluoromethyl radicals have the corresponding radicals R' i hydroxy It can be obtained by the action of a fluorinating agent on a heterocyclylalkyl piperidine derivative representing a methyl radical. This reaction can be carried out under the fluorination conditions described above for the addition of the radical Re, which means fluorine.
    [83] Heterocyclylalkyl piperidine derivatives of formula (II) in which R 1 , R ' 1 , R' 2 , R ' 3 , R' 4 or R ' 5 represent alkylthiomethyl or cycloalkylthiomethyl radicals represent It can be obtained by reacting a thiol corresponding to a heterocyclylalkyl piperidine derivative wherein i is halomethyl (halogen is preferably a bromine or chlorine atom). This reaction is generally carried out at temperatures between 20 ° C. and the reflux temperature of the reaction mixture, in the presence of an acid acceptor such as trialkylamine (eg triethylamine) or alkali metal hydride (eg sodium hydride), ether (eg : Inert solvents such as tetrahydrofuran or dioxane), amides (eg N, N-dimethylformamide) or dimethyl sulfoxide.
    [84] Heterocyclylalkyl piperidine derivatives having a halomethyl radical R ' i can be prepared from the corresponding derivatives where R' i is a hydroxymethyl radical, by the action of a halogenating agent (halophosphorus derivative or thionyl chloride). . This reaction is carried out at temperatures from 0 ° C. to 60 ° C., optionally in the presence of a base such as pyridine, optionally in an inert solvent such as dichloromethane.
    [85] R 1, R '1, R ' 2, R '3, R' 4 or R '5 radical heterocyclylalkyl piperidine derivatives of formula (II) represents a -CH 2 -NRaRb will be modified radical R' i is It can be obtained by the action of an amine HNRaRb on a heterocyclylalkyl piperidine derivative which is halomethyl (halogen is preferably a bromine or chlorine atom). The reaction is carried out at temperatures between 20 ° C. and the reflux temperature of the reaction mixture, in the presence of an acid acceptor such as trialkylamine (eg triethylamine) or alkali metal hydride (eg sodium hydride), ether (eg tetra Hydrofuran or dioxane), amides such as N, N-dimethylformamide or dimethyl sulfoxide.
    [86] R 1, R '1, R ' 2, R '3, R' 4 or R i is halomethyl, 5 heterocyclylalkyl of formula II represents a carboxymethyl radical piperidine derivatives are the radicals R to be transformed ( Halogen is preferably a bromine or chlorine atom), which can be obtained by the action of an alkaline cyanide on a heterocyclylalkyl piperidine derivative followed by hydrolysis of the nitrile. The reaction is carried out at temperatures between 0 ° C. and the boiling point of the reaction mixture, using sodium cyanide or potassium cyanide in an organic solvent or water-alcohol mixture such as dimethyl sulfoxide or dimethylformamide, and then between 0 ° C. and the boiling point of the reaction mixture. At a temperature of, optionally reacted with a strong acid, such as hydrochloric acid, in the presence of a lower aliphatic alcohol.
    [87] Heterocycle of Formula II wherein R 1 , R ' 1 , R' 2 , R ' 3 , R' 4 or R ' 5 represent alkoxycarbonylmethyl, cycloalkyloxycarbonylmethyl or -CH 2 -CO-NRaRb radicals The arylalkyl piperidine derivative can be obtained from the corresponding acid, in particular in the presence of a binder such as carbodiimide as described above, according to a conventional method of converting an acid to an ester or an amide without affecting the rest of the molecule. have.
    [88] Heterocyclic derivatives of the formula (III) in which Hal is a bromine atom, R i as described above, X 1 to X 4 each represent> C—R ′ 1 to> C—R ′ 4 , and X 5 represents> CH are 20 ° C. At temperatures of from 115 ° C., it can be prepared by bromination of the corresponding 4-hydroxyquinoline with a brominating agent such as phosphorus oxytribromide or thionyl bromide without solvent.
    [89] 4-hydroxyquinoline can be prepared by decarboxylation of the corresponding 3-carboxy-4-hydroxyquinoline in a solvent such as diphenyl ether at a temperature of 100 ° C. to 260 ° C.
    [90] 3-carboxy-4-hydroxyquinoline can be prepared in a manner analogous to the method described in EP-A0 379 412, starting with the desired anil derivative.
    [91] A heterocyclic derivative of formula III wherein Hal is a bromine atom, R 1 is as described above, X 1 to X 4 each represent> C—R ′ 1 to> C—R ′ 4 , and X 5 represents>C—Cl; The corresponding 3-chloro-4-hydroxyquinoline can be prepared by bromination. This bromination is usually carried out with triphenylphosphine dibromide in acetonitrile at a temperature of 20 ° C to 85 ° C.
    [92] 3-chloro-4-hydroxyquinoline can be prepared by chlorination of 4-hydroxyquinoline. Chlorination is carried out using N-chlorosuccinimide in a solvent such as acetic acid, for example, at a temperature of 20 ° C. to 100 ° C.
    [93] Heterocyclic derivative of formula III wherein Hal is a bromine atom, R 1 is as described above, X 1 to X 4 each represent> C-R ' 1 to>C-R' 4 , and X 5 represents> C-COCF 3 Can be prepared by bromination of the corresponding 4-hydroxy-3-fluoroacetylquinoline derivatives, in a manner analogous to the preparation of derivatives in which X 5 represents> CH. This reaction is carried out using a brominating agent such as phosphorus oxytribromide at a temperature of 20 ° C. to 115 ° C. without solvent. 4-hydroxy-3-trifluoroacetylquinoline can be prepared by a similar method as described for the preparation of 3-carboxy-4-hydroxyquinoline.
    [94] Heterocyclic derivatives of formula III wherein Hal is an iodine atom, R 1 is a methoxy radical, X 1 to X 4 each represent> C—R ′ 1 to> C—R ′ 4 and X 5 represents> CF are described in [ See E. Arzel et al., Tetrahedron, 55 , 12149-12156 (1999), according to a method analogous to that of base and iodine, starting with 3-fluoro-6-methoxyquinoline as starting material. Can be prepared. For example, at a temperature of -80 ° C to 20 ° C, lithium diisopropylamide in a solvent such as ether (tetrahydrofuran) is used. 3-fluoro-6-methoxyquinoline is 6-methoxyquinoline diazonium 3-tetra-fluoroborate or 3- according to Balz-Schieman reaction (Org. Synth., Coll 5, 133 (1973)). Hexafluorophosphate can be obtained by pyrolysis at a temperature of 100 ° C to 240 ° C. 6-methoxyquinoline diazonium 3-tetra-fluoroborate or 6-methoxy-quinoline diazonium 3-hexafluorophosphate is derived from 3-amino-6-methoxyquinoline, see A. Roe et al. , J. Am. Chem. Soc., 71, 1785-86 (1949), in an acidic medium (tetrafluoroboric acid or hexafluorophosphor) in a solvent such as water at a temperature of -10 ° C to + 20 ° C Alkaline nitrile (e.g. sodium nitrite) in acid) or alkyl nitrite (e.g. isoamyl nitrite) in a solvent such as ether (e.g. tetrahydrofuran) at a temperature of -10 ° C to + 10 ° C and It can be prepared by reacting a trifluoroborate / diethyl ether complex. 3-amino-6-methoxyquinoline is described in N. Heindel, J. Med. Chem. (1970) 13,760.
    [95] Hal is a bromine atom, R 1 is as described above, X 2 to X 4 each represent> C—R ′ 2 to> C—R ′ 4 , X 1 represents a nitrogen atom, or optionally X 1 , X 3 and Heterocyclic derivatives of formula (III) wherein X 4 represents> C-R ' 1 ,>C-R' 3 and> C-R ' 4 , X 2 represents a nitrogen atom and X 5 represents> CH or> C-Cl are 3 -Aminopyridine as starting material, prepared in the same manner as described above in the case where X 1 to X 4 each represent> C-R ' 1 to>C-R' 4 , or in the case of 1,5-naphthyridine; Adams JT et al., J. Am. Chem. Soc., 68 , 1317 (1946), for 1,7-naphthyridine, see S. Radl et al., Collect. Czech. Chem. Commun., 56 , 2420 (1991). The hydroxynaphthyridine required to carry out this reaction is also prepared in a similar manner as described for hydroxyquinoline, starting with 3-aminopyridine or substituted derivatives thereof. 3-aminopyridine derivatives may be obtained by applying the methods described in The Chemistry of Heterocyclic Compounds, Vol. 14, Pyridines and its derivatives, Suppliment Part III, page 41. Ed. RA Abramovitch, InterScience Publication. Can be.
    [96] Hal is a bromine atom, R 1 is as defined above, X 1 , X 2 and X 4 represent> C-R ' 1 ,>C-R' 2 and> C-R ' 4 , X 3 represents a nitrogen atom, and X Heterocyclic derivatives of formula (III) in which 5 represents> CH or> C-Cl are derived from 2-aminopyridine or substituted derivatives thereof, wherein X 1 to X 4 are each> C-R ' 1 to>C-R' 4 Can be prepared by methods analogous to those described above, or by the synthesis methods described in D. Heber et al., Arzneim-Forsch, 44 , 809 (1994). 2-aminopyridine can be obtained by applying the methods described in The Chemistry of Heterocyclic Compounds, Vol. 14, Pyridines and its derivatives, Suppliment Part III, page 41. Ed. RA Abramovitch, InterScience Publication. have.
    [97] Derivatives of formula III wherein Hal is a bromine atom, R 1 is as defined above and X 5 represents a nitrogen atom are described in J. Am. Chem. Soc., 69 , 184 (1947), which may be obtained from 2-amino-benzeneamide. 2-amino-benzeneamide is closed in the presence of an alkyl orthoformate, such as ethyl orthoformate, in a solvent such as diethylene glycol at a temperature of 105 ° C. to 120 ° C. to produce 4-hydroxyquinazolin. Bromine as described above. 2-amino-benzeneamides are described in V. Snieckus, Chem. Rev., 90 , 879 (1990) and Pure Appl. Chem., 62 , 2047 (1990), is applied or applied to obtain from the corresponding aniline.
    [98] Heterocyclic derivatives of formula III wherein Hal is a bromine atom, R 1 is as defined above and X 4 is a nitrogen atom are described in Synth. Commun., 19 , 3087 (1989), which may be obtained from 2-acetylaniline. The 4-hydroxycinnoline obtained is brominated under the conditions described above. 2-acetyl-aniline is obtained from the corresponding aniline by applying the process described above for 2-aminobenzeneamide.
    [99] Piperidine derivatives of formula IV, wherein n is 0 and R " 2 represents carboxyl, can be used in solvents such as ethers (e.g. tetrahydrofuran) at temperatures of 0 ° C. to 100 ° C. In the presence of isopropylamide or lithium hexamethyldisilylamide), by reaction of piperidine derivatives with vinyl phenyl sulfoxide, Koppel, J. Chem. Soc. Chem. Commun., 473 (1975) In a manner analogous to the method described in the following, it can be prepared from the corresponding piperidine derivative of formula (V):
    [100]
    [101] In the above formula,
    [102] R ″ 2 is as described above and protected in advance,
    [103] Rz is as described above.
    [104] The intermediate product obtained is then pyrolyzed to a temperature of 60 ° C. to 150 ° C. in an inert solvent such as chloroform, tetrahydrofuran, toluene or xylene. Rz is advantageously a protecting group for a nitrogen atom, for example t-butyloxycarbonyl.
    [105] Piperidine derivatives of formula IV wherein n is 1 or 2 and R ″ 2 represents carboxyl are analogous to the methods described below in the Examples from corresponding piperidine derivatives of formula V wherein R ″ divalent protection is It can be prepared according to. In particular, this process involves a base such as lithium diisopropylamide or n-butyllithium in a solvent such as ether (e.g. tetrahydrofuran), followed by an alkenyl halide (allyl halide or 1-halo-3-butene) is carried out continuously.
    [106] n is as defined above and R " 2 is alkyloxycarbonyl, cycloalkyloxycarbonyl, -CO-NRaRb, alkyloxycarbonylmethyl, alkyloxycarbonylethyl, cycloalkyloxycarbonylmethyl, cycloalkyloxycarbonyl Piperidine derivatives of formula IV wherein ethyl, -CH 2 -CONRaRb or-(CH 2 ) 2 -CONRaRb or R 2 in R 2 represent alkyloxycarbonyl, cycloalkyloxycarbonyl or -CO-NRaRb are the remainder of the molecule The esters can be prepared from the corresponding carboxylic acids according to conventional methods of conversion to esters or amides without affecting the moieties .. The esters can be prepared from ethers (eg tetrahydrofuran or dioxane) at 0 ° C. to the reflux temperature of the reaction mixture, Carbodiimide (e.g., N, N'-dicyclo-carbodiimide) in amide (e.g. dimethylformamide) or chlorinated solvent (e.g., dichloromethane, 1,2-dichloroethane or chloroform) or N Prepared in the presence of a binder such as, N'-carbonyldiimidazole. Amides are prepared by reacting the corresponding amines under the same conditions as described above, in particular the preparation of derivatives in which R < 2 > In case, see Saha et al., J. Chem. Soc. Perkin I, 505 (1985), is prepared by reacting diazoalkanes (eg diazomethane) in ethers (eg diethyl ether) at temperatures between -10 ° C and 5 ° C.
    [107] n is as defined above, and piperidine derivatives of formula IV wherein R ″ 2 represents cyano, —CH 2 —CN or — (CH 2 ) 2 —CN are described in Bieron et al., Zabicky “The chemistry of amides "Wiley, pp. 274-283 (1970)] can be prepared by applying a dehydrating agent to the corresponding amide. The reaction is carried out at temperatures between 20 ° C. and the reflux temperature of the reaction mixture. In the presence of phosphorus pentoxide or phosphorus oxychloride in or without solvent.
    [108] Piperidine derivatives of formula (IV) wherein n is as defined above and R ″ 2 represents hydroxymethyl, cynomethyl or carboxymethyl, at a temperature of 20 ° C. to 60 ° C., a solvent such as ether (e.g. tetrahydrofuran) Hydrides such as lithium aluminum hydride or diisobutylaluminum hydride to a piperidine derivative of formula VI to prepare a piperidine derivative wherein R " 2 is hydroxymethyl. According to conventional methods without affecting, it can be prepared by converting hydroxymethyl radicals to cynomethyl radicals followed by carboxymethyl radicals:
    [109]
    [110] In the above formula,
    [111] Rz and n are as defined above,
    [112] Ry represents a protective radical that readily hydrolyzes.
    [113] If Ry represents a radical which is readily hydrolyzed, it may in particular be selected from alkyl (straight or branched chain of 1 to 4 carbon atoms), benzyl, cycloalkyl, phenylpropyl and allyl.
    [114] The conversion to an acid can be effected, in particular, by the action of a halogenating agent such as thionylchloride or phosphorus trichloride or tribromide from the latter compound or in alkanesulfonyl chloride (eg methanesulfonyl chloride or p in an inert solvent such as dichloromethane). -Toluenesulfonyl chloride) followed by alkaline cyanide (e.g. potassium cyanide or sodium cyanide), followed by hydrolysis. The halogenation reaction is carried out in a chlorinated solvent (eg dichloromethane or chloroform) at a temperature between 0 ° C. and the reflux temperature of the reaction mixture. The reaction of alkaline cyanide can be carried out at temperatures between 20 ° C. and the reflux temperature of the reaction mixture, with dimethyl sulfoxide, amides such as dimethylformamide, ketones such as acetone, ethers such as tetrahydrofuran or alcohols. Eg methanol or ethanol). Nitrile is obtained in accordance with conventional methods which do not affect the rest of the molecule, in particular the esters obtained after the action of hydrochloric acid in a methanolic medium at temperatures between 20 ° C. and 70 ° C., for example sodium hydroxide in a mixture of dioxane and water. Saponification, or hydrolysis by direct action of aqueous sulfuric acid at a temperature of from 50 ° C to 80 ° C.
    [115] Piperidine derivatives of formula IV wherein n and Rz are as defined above and R ″ divalent represents 2-carboxyethyl radicals are halo derivatives prepared as described above from derivatives of formula IV wherein R ″ divalent hydroxymethyl radicals It can be prepared by combining with sodium salt of diethyl malonate followed by acidic hydrolysis in the aqueous medium of the product obtained.
    [116] Piperidine derivatives of formula IV, wherein n and Rz are as defined above and R ″ 2 represents carboxyhydroxymethyl or carboxycarbonyl, see M. Mizuno et al., Tetrahedron Lett. 39 , 9209 (1998) The method described in [] can be applied to halogenate piperidine derivatives of formula (VII):
    [117]
    [118] In the above formula,
    [119] Rz and n are as defined above.
    [120] The reaction is carried out at a temperature of −50 to 10 ° C., in the presence of an organic base (eg triethylamine) in ether (eg tetrahydrofuran), such as dialkyl phosphorocyanidate (eg diethyl phosphorocyanidate). Is carried out. The intermediate dicyanophosphate obtained is then hydrolyzed in an acidic medium (eg concentrated hydrochloric acid) in a polar solvent (eg water) at the reflux temperature of the reaction mixture. Derivatives wherein R ″ 2 is carboxycarbonyl are subjected to the process described in Burhardt et al., Tetrahedron Lett., 29 , 3433 (1988), to hydrolyze the product obtained after oxidation of the corresponding ester. Triacetoxy-1,1-dihydro-1,2-benzoiodoxol, especially in solvents such as nitrile or chlorinated derivatives (e.g. acetonitrile or dichloromethane) at temperatures between 0 and 40 ° C. A oxidizing agent such as -3 (1H) one followed by hydrolysis by reaction of a base (e.g. sodium hydroxide) in an aqueous-alcoholic solvent (e.g. water-methanol) at a temperature between 20 ° C and the reflux temperature of the reaction mixture. Do it.
    [121] Piperidine derivatives of Formula IV, wherein n and Rz are as defined above and R ″ 2 represents -CF 2 -Rc, see M. Parisi et al., J. Org. Chem., 60 , 5174 (1995). In a similar manner to that described in)], a fluorinating agent is applied to a piperidine derivative of formula IV wherein R ″ 2 is a radical -CO-Rc and Rc is an ester, and then a piperidine derivative wherein Rc is carboxy If necessary, it can be prepared by hydrolysis of the ester. Fluorination conditions are similar to those described above for the preparation of derivatives in which Re in Y is a fluorine atom. Hydrolysis is carried out by reacting the base in an aqueous-alcoholic solvent under the conditions described above.
    [122] Piperidine derivatives of formula IV wherein n and Rz are as defined above and R ″ 2 represents the radical —CH═CH—Rc are described in Org. Synth. Coll., Vol. II, p. 541, Coll. Vol. 5 p. 242] is applied to oxidize an aldehyde of a derivative of formula IV wherein R ″ 2 represents a hydroxymethyl radical, and then the Wittig method is used to apply R ″ 2 to -CH = CH-Rc. And an ester obtained by hydrolysis with an acid, optionally followed by hydrolysis with an acid, oxidation of the base (e.g. pyridine) in a chlorinated solvent (e.g. dichloromethane) at a temperature of 0-20 [deg.] C. In the presence of an acidic medium (e.g. sulfuric acid), a polar solvent (e.g. water) or an oxidizing agent (e.g. potassium dichromate) in chromium oxide, the conversion to unsaturated derivatives is described in Johnson in " Ylid Chemistry "Academic Press (1966). At temperatures between the reflux temperatures of the mixtures, the reaction is carried out by reacting phosphorus lide (eg carbetoxymethylenetriphenylphosphorane) in a hydrocarbon (eg toluene) The hydrolysis is carried out according to the method described above.
    [123] Piperidine derivatives of formula IV wherein n and Rz are as defined above and R ″ 2 represents a radical C (CH 3 ) 2 Rc or —C (cycloalk) Rc are esters of R ″ divalent acid, —CH 2 COOH From derivatives of Formula IV, Ashutosh et al., Tetrahedron Lett., 40 , 4733 (1999) and Sauers, J. Org. Chem. 57 , 671 (1992), after application of the process described herein, optionally obtained esters can be prepared by hydrolysis. This reaction particularly involves amides such as lithium diisopropylamide followed by methyl halides such as methyl iodide or derivatives of Hal-Alk-Hal, where Hal is preferably a bromine atom. At temperatures of < RTI ID = 0.0 > C, < / RTI > it is carried out by continuous action in a polar solvent such as hexamethylphosphorotriamide.
    [124] The process described above for the preparation of piperidine derivatives of formula IV also involves first combining piperidine with a heterocyclic derivative of formula III and then converting the radical R 2 under the conditions described above to a derivative of formula II. It will be appreciated that it is applicable.
    [125] It will also be understood that the methods described below in the Examples form part of the present invention.
    [126] It will be appreciated that the derivatives of formulas (I) and (II) may be in enantiomer or diastereomeric form or may exist in syn or anti form. Enantiomers or diastereomers and syn or anti forms and mixtures thereof are also within the scope of the present invention. These forms can be separated according to conventional methods, in particular by chromatography on silica or by high performance liquid chromatography (HPLC).
    [127] Heterocyclylalkyl piperidine derivatives of formula (I) can be purified by physical methods such as crystallization or chromatography if necessary.
    [128] Heterocyclylalkyl piperidine derivatives of formula (I) can be converted to addition salts with acids by known methods if necessary. It will be understood that these salts also fall within the scope of the present invention.
    [129] Examples of addition salts with pharmaceutically acceptable acids include inorganic acids (hydrochloride, hydrobromide, sulfates, nitrates and phosphates) or organic acids (succinate, fumarate, tartrate, acetate, propionate, maleate, citrate Salts formed with methanesulfonate, ethanesulfonate, phenylsulfonate, p-toluenesulfonate, isethionate, naphthylsulfonate or camphorsulfonate or substituted derivatives of these compounds).
    [130] Some of the heterocyclylalkyl piperidine derivatives of formula (I) having carboxyl radicals can be converted to metal salts or to addition salts with nitrogen bases according to known methods. These salts also fall within the scope of the present invention. The salt may be reacted with a metal base (e.g. alkali metal or alkaline-earth metal), ammonia or amine in a solvent (e.g. alcohol, ether or water) suitable for the product according to the invention or by exchange reaction with an organic acid salt. Can be obtained. The salt formed is precipitated, optionally by concentration of the solution and separated by filtration, sedimentation or lyophilization. Examples of pharmaceutically acceptable salts that may be mentioned are alkali metals (sodium, potassium or lithium) or alkaline-earth metals (magnesium or calcium), ammonium salts or nitrogen bases (ethanolamine, diethanolamine, trimethylamine, triethyl Amine, methylamine, propylamine, diisopropylamine, N, N-dimethylethanolamine, benzylamine, dicyclohexylamine, N-benzyl-β-feethylamine, N, N'-dibenzylethylenediamine, di Phenylenediamine, benzhydrylamine, quinine, choline, arginine, lysine, leucine or dibenzylamine) salts.
    [131] Heterocyclylalkyl piperidine derivatives according to the invention are particularly advantageous antibacterial agents.
    [132] In vitro, the heterocyclylalkyl piperidine derivatives according to the invention can be applied to methicillin-resistant Staphylococcus aureus at a concentration of, for example, from 0.03 μg / ml to 4 μg / ml for Gram positive microorganisms. aureus) AS5155, and for most of them, was found to exhibit activity at concentrations of 0.3 μg / ml to 8 μg / ml in Streptococcus pneumoniae 625401. They have also been found to be active against Gram-negative microorganisms, for example, but not limited to, at Moraxella catarrhalis at concentrations from 0.12 μg / ml to 64 μg / ml. In vivo, these compounds were orally administered to mice infected with Staphylococcus aureus IP8203 subcutaneously at a dose of 18 mg / kg to 150 mg / kg (DC 50 ) or at a dose of 20 mg / kg to 150 mg / kg. It was found to show activity when administered.
    [133] Finally, the products of the invention are advantageous in view of their particularly low toxicity. None of the products were shown to be toxic when injected subcutaneously into mice at a dose of 100 mg / kg.
    [134] In formula (I), X 1 , X 2 , X 3 , X 4 and X 5 each represent> C—R ′ 1 to> C—R ′ 5 , or optionally only one of them represents a nitrogen atom,
    [135] R 1 , R ' 1 , R' 2 , R ' 3 , R' 4 and R ' 5 are the same or different and represent a hydrogen or halogen atom or an alkyl or alkyloxy radical or substituted by alkyloxy Indicates,
    [136] R 2 represents carboxyl, alkyloxycarbonyl or -CONRaRb, where Ra represents a hydrogen atom and Rb represents a hydrogen atom or a hydroxyl radical, or
    [137] R 2 represents hydroxymethyl, alkyl or alkyloxycarbonyl containing 1 or 2 carbon atoms substituted by carboxyl,
    [138] R 3 represents a radical alk-R o 3 where alk represents an alkyl radical and R o 3 represents hydrogen, cycloalkyl, cycloalkylthio, phenyl, phenoxy, phenylthio, phenylamino, heterocyclyloxy or heterocycle Arylthio, or optionally R o 3 represents -CR'b = CR'c-R'a, wherein R'a represents phenyl and R'b and R'c represent hydrogen;
    [139] Y represents the radical> CH-Re, where Re is hydrogen, fluoro or hydroxyl,
    [140] n is an integer from 2 to 3,
    [141] It is understood that it is particularly advantageous that the phenyl or heterocyclyl radicals or moieties described above may be optionally substituted by rings having 1 to 4 halogens.
    [142] In particular the heterocyclylalkyl piperidine derivatives of the formula (I) are as follows:
    [143] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] piperidine-4-carboxylic acid
    [144] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) ethyl] piperidine-4-carboxylic acid
    [145] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- (2-thiazole-2-thioethyl) piperidine-4-carboxylic acid
    [146] 1- (2-cyclopentylthioethyl) -4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylic acid
    [147] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- (3-phenylaryl) piperidine-4-carboxylic acid and salts thereof.
    [148] More particularly mentioned products according to the invention are the heterocyclylalkyl piperidine derivatives of formula (I) and the following formula:
    [149] 4- [3- (3-Chloro-6-methoxyquinolin-4-yl) propyl] -1-heptyl-piperidine-4-carboxylic acid
    [150] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4-phenyl-butyl] piperidine-4-carboxylic acid
    [151] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (2-fluorophenyl) propyl] piperidine-4-carboxylic acid
    [152] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (3-fluorophenyl) propyl] piperidine-4-carboxylic acid
    [153] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenyl) propyl] piperidine-4-carboxylic acid
    [154] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (4-fluorophenyl) butyl] piperidine-4-carboxylic acid
    [155] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenyl) propyl] piperidine-4-carboxylic acid
    [156] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (2,3-difluorophenyl) propyl] piperidine-4-carboxylic acid
    [157] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluorophenyl) propyl] piperidine-4-carboxylic acid
    [158] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (2,6-difluorophenyl) propyl] piperidine-4-carboxylic acid
    [159] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-difluorophenyl) propyl] piperidine-4-carboxylic acid
    [160] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) propyl] piperidine-4-carboxylic acid
    [161] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) propyl] piperidine-4-carboxylic acid
    [162] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) propyl] piperidine-4-carboxylic acid
    [163] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3-phenyl-thiopropyl] piperidine-4-carboxylic acid
    [164] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenylthio) propyl] piperidine-4-carboxylic acid
    [165] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenylthio) propyl] piperidine-4-carboxylic acid
    [166] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-fluorophenylthio) ethyl] piperidine-4-carboxylic acid
    [167] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenylthio) propyl] piperidine-4-carboxylic acid
    [168] 4- [3- (3-Chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3-difluorophenylthio) ethyl] -piperidine-4-carboxylic acid
    [169] 4- [3- (3-Chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenylthio) propyl] -piperidine-4-carboxylic acid
    [170] 4- [3- (3-Chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,6-difluorophenylthio) ethyl] -piperidine-4-carboxylic acid
    [171] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylthio) ethyl] -piperidine-4- Carboxylic acid
    [172] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylthio) ethyl] -piperidine-4- Carboxylic acid
    [173] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylthio) ethyl] -piperidine-4- Carboxylic acid
    [174] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy) ethyl] -piperidine-4- Carboxylic acid
    [175] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenoxy) ethyl] -piperidine-4- Carboxylic acid
    [176] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenoxy) ethyl] -piperidine-4- Carboxylic acid
    [177] 4- [3- (3-Chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino) ethyl] -piperidine-4-carboxylic acid
    [178] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylamino) ethyl] -piperidine-4- Carboxylic acid
    [179] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylamino) ethyl] -piperidine-4- Carboxylic acid
    [180] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylamino) ethyl] -piperidine-4- Carboxylic acid
    [181] 4- [3- (3-Chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluorophenylthio) propyl] -piperidine-4-carboxylic acid
    [182] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2-chlorophenylthio) ethyl] piperidine-4-carboxylic acid
    [183] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chlorophenylthio) propyl] piperidine-4-carboxylic acid
    [184] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3-chlorophenylthio) ethyl] piperidine-4-carboxylic acid
    [185] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorophenylthio) propyl] piperidine-4-carboxylic acid
    [186] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-chlorophenylthio) ethyl] piperidine-4-carboxylic acid
    [187] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chlorophenylthio) propyl] piperidine-4-carboxylic acid
    [188] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2-methylphenylthio) ethyl] piperidine-4-carboxylic acid
    [189] 4- [3- (3-Chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methylphenylthio) propyl] -piperidine-4-carboxylic acid
    [190] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methylphenylthio) ethyl] piperidine-4-carboxylic acid
    [191] 4- [3- (3-Chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylphenylthio) propyl] -piperidine-4-carboxylic acid
    [192] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-methylphenylthio) ethyl] piperidine-4-carboxylic acid
    [193] 4- [3- (3-Chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methylphenylthio) propyl] -piperidine-4-carboxylic acid
    [194] 4- [3- (3-Chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2-trifluoromethylphenylthio) ethyl] -piperidine-4-carboxylic acid
    [195] 4- [3- (3-Chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-trifluoromethylphenylthio) propyl] -piperidine-4-carboxylic acid
    [196] 4- [3- (3-Chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3-trifluoromethylphenylthio) ethyl] -piperidine-4-carboxylic acid
    [197] 4- [3- (3-Chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethylphenylthio) propyl] -piperidine-4-carboxylic acid
    [198] 4- [3- (3-Chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-trifluoromethylphenylthio) ethyl] -piperidine-4-carboxylic acid
    [199] 4- [3- (3-Chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-trifluoromethylphenylthio) propyl] -piperidine-4-carboxylic acid
    [200] 4- [3- (3-Chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2-methoxyphenylthio) ethyl] -piperidine-4-carboxylic acid
    [201] 4- [3- (3-Chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxyphenylthio) propyl] -piperidine-4-carboxylic acid
    [202] 4- [3- (3-Chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methoxyphenylthio) ethyl] -piperidine-4-carboxylic acid
    [203] 4- [3- (3-Chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxyphenylthio) propyl] -piperidine-4-carboxylic acid
    [204] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-methoxyphenylthio) ethyl] piperidine-4-carboxylic acid
    [205] 4- [3- (3-Chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methoxyphenylthio) propyl] -piperidine-4-carboxylic acid
    [206] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [cyclopentylmethyl] piperidine-4-carboxylic acid
    [207] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentyl) ethyl] piperidine-4-carboxylic acid
    [208] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine-4-carboxylic acid
    [209] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclopentylthio) propyl] piperidine-4-carboxylic acid
    [210] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclohexylthio) propyl] piperidine-4-carboxylic acid
    [211] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (thien-2-yl) butyl] piperidine-4-carboxylic acid
    [212] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) thiopropyl] piperidine-4-carboxylic acid
    [213] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) propyl] piperidine-4-carboxylic acid
    [214] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (thien-3-yl) butyl] piperidine-4-carboxylic acid
    [215] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-3-yl) thioethyl] piperidine-4-carboxylic acid
    [216] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) thiopropyl] piperidine-4-carboxylic acid
    [217] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-2-yl) propyl] piperidine-4-carboxylic acid
    [218] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (1,3-thiazol-2-yl) butyl] piperidine-4-carboxylic acid
    [219] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-2-yl) thioethyl] piperidine-4-carboxylic acid
    [220] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-2-yl) propyl] piperidine-4-carboxylic acid
    [221] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrid-2-yl) butyl] piperidine-4-carboxylic acid
    [222] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-2-yl) thiopropyl] piperidine-4-carboxylic acid
    [223] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-3-yl) propyl] piperidine-4-carboxylic acid
    [224] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrid-3-yl) butyl] piperidine-4-carboxylic acid
    [225] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-3-yl) thioethyl] piperidine-4-carboxylic acid
    [226] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-3-yl) thiopropyl] piperidine-4-carboxylic acid
    [227] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-4-yl) propyl] piperidine-4-carboxylic acid
    [228] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrid-4-yl) butyl] piperidine-4-carboxylic acid
    [229] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-4-yl) thioethyl] piperidine-4-carboxylic acid
    [230] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-4-yl) thiopropyl] piperidine-4-carboxylic acid
    [231] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) propyl] piperidine-4-carboxylic acid
    [232] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrazin-2-yl) butyl] piperidine-4-carboxylic acid
    [233] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrazin-2-yl) thioethyl] piperidine-4-carboxylic acid
    [234] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) thiopropyl] piperidine-4-carboxylic acid
    [235] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenyl) prop-2-ynyl] piperidine-4-carboxylic acid
    [236] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4-difluorophenyl) prop-2-ynyl] piperidine-4 Carboxylic acid
    [237] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4-difluorophenyl) prop-2-ynyl] piperidine-4 Carboxylic acid
    [238] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) prop-2-ynyl] piperidine 4-carboxylic acid
    [239] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) prop-2-ynyl] piperidine 4-carboxylic acid
    [240] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) prop-2-ynyl] piperidine 4-carboxylic acid
    [241] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-3-fluorophenyl) prop-2-ynyl] piperidine- 4-carboxylic acid
    [242] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-4-fluorophenyl) prop-2-ynyl] piperidine- 4-carboxylic acid
    [243] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-4-fluorophenyl) prop-2-ynyl] piperidine- 4-carboxylic acid
    [244] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-5-fluorophenyl) prop-2-ynyl] piperidine- 4-carboxylic acid
    [245] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-2-fluorophenyl) prop-2-ynyl] piperidine- 4-carboxylic acid
    [246] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluoro-4-methylphenyl) prop-2-ynyl] piperidine-4 Carboxylic acid
    [247] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-bis (trifluoromethyl) phenyl) prop-2-ynyl] pi Ferridine-4-carboxylic acid
    [248] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperidine-4-carboxylic acid
    [249] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) prop-2-ynyl] piperidine-4-carboxylic acid
    [250] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-2-yl) prop-2-ynyl] piperidine 4-carboxylic acid
    [251] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-4-yl) prop-2-ynyl] piperidine 4-carboxylic acid
    [252] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-5-yl) prop-2-ynyl] piperidine 4-carboxylic acid
    [253] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-2-yl) prop-2-ynyl] piperidine-4-carboxylic acid
    [254] 4- [3- (3-Chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-3-yl) prop-2-ynyl] piperidine-4-carboxylic acid
    [255] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-4-yl) prop-2-ynyl] piperidine-4-carboxylic acid
    [256] 4- [3- (3-Methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine-4-carboxylic acid
    [257] 4- [3- (3-Methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine-4-carboxylic acid
    [258] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) propyl] piperidine-4-carboxylic acid
    [259] 4- [3- (3-Methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino) ethyl] -piperidine-4-carboxylic acid
    [260] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylamino) ethyl] -piperidine-4- Carboxylic acid
    [261] 4- [3- (3-Methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) ethyl] -piperidine-4-carboxylic acid
    [262] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy) ethyl] -piperidine-4- Carboxylic acid
    [263] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine-4-carboxylic acid
    [264] 4- [3- (3-Methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl] piperidine-4-carboxylic acid
    [265] 4- [3- (3-Methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] piperidine-4-carboxylic acid
    [266] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) prop-2-ynyl] piperidine 4-carboxylic acid
    [267] 4- [3- (3-Methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperidine-4-carboxylic acid
    [268] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) propyl] piperidine-4-carboxylic acid
    [269] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino) ethyl] piperidine-4-carboxylic acid
    [270] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylamino) ethyl] piperidine-4- Carboxylic acid
    [271] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) ethyl] piperidine-4-carboxylic acid
    [272] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy) ethyl] piperidine-4- Carboxylic acid
    [273] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylthio) ethyl] piperidine-4- Carboxylic acid
    [274] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl] piperidine-4-carboxylic acid
    [275] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) prop-2-ynyl] piperi Dean-4-carboxylic acid
    [276] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperidine-4-carboxylic acid
    [277] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine-4-carboxylic acid
    [278] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine-4-carboxylic acid
    [279] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) propyl] piperidine-4-carboxylic acid
    [280] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino) ethyl] piperidine-4-carboxylic acid
    [281] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylamino) ethyl] piperidine-4- Carboxylic acid
    [282] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) ethyl] piperidine-4-carboxylic acid
    [283] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy) ethyl] piperidine-4- Carboxylic acid
    [284] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylthio) ethyl] piperidine-4- Carboxylic acid
    [285] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine-4-carboxylic acid
    [286] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl] piperidine-4-carboxylic acid
    [287] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] piperidine-4-carboxylic acid
    [288] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) prop-2-ynyl] piperi Dean-4-carboxylic acid
    [289] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperidine-4-carboxylic acid
    [290] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine-4-carboxylic acid
    [291] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine-4-carboxylic acid
    [292] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) propyl] piperidine-4- Carboxylic acid
    [293] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino) ethyl] piperidine-4-carboxylic acid
    [294] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylamino) ethyl] piperidine-4 Carboxylic acid
    [295] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) ethyl] piperidine-4-carboxylic acid
    [296] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy) ethyl] piperidine-4 Carboxylic acid
    [297] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylthio) ethyl] piperidine-4 Carboxylic acid
    [298] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine-4-carboxylic acid
    [299] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl] piperidine-4-carboxylic acid
    [300] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] piperidine-4-carboxylic acid
    [301] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) prop-2-ynyl] pi Ferridine-4-carboxylic acid
    [302] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperidine-4- Carboxylic acid
    [303] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine-4-carboxylic acid
    [304] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine-4-carboxylic acid
    [305] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) propyl] piperidine-4- Carboxylic acid
    [306] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino) ethyl] piperidine-4-carboxylic acid
    [307] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylamino) ethyl] piperidine-4 Carboxylic acid
    [308] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) ethyl] piperidine-4-carboxylic acid
    [309] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy) ethyl] piperidine-4 Carboxylic acid
    [310] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylthio) ethyl] piperidine-4 Carboxylic acid
    [311] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine-4-carboxylic acid
    [312] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl] piperidine-4-carboxylic acid
    [313] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] piperidine-4-carboxylic acid
    [314] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) prop-2-ynyl] pi Ferridine-4-carboxylic acid
    [315] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperidine-4- Carboxylic acid
    [316] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine-4-carboxylic acid
    [317] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine-4-carboxylic acid
    [318] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) propyl] piperidine-4-carboxylic acid
    [319] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino) ethyl] piperidine-4-carboxylic acid
    [320] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylamino) ethyl] piperidine-4- Carboxylic acid
    [321] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) ethyl] piperidine-4-carboxylic acid
    [322] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy) ethyl] piperidine-4- Carboxylic acid
    [323] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylthio) ethyl] piperidine-4- Carboxylic acid
    [324] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine-4-carboxylic acid
    [325] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl] piperidine-4-carboxylic acid
    [326] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] piperidine-4-carboxylic acid
    [327] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) prop-2-ynyl] piperi Dean-4-carboxylic acid
    [328] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperidine-4-carboxylic acid
    [329] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine-4-carboxylic acid
    [330] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine-4-carboxylic acid
    [331] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) propyl] piperidine-4 Carboxylic acid
    [332] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino) ethyl] piperidine-4- Carboxylic acid
    [333] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylamino) ethyl] piperidine- 4-carboxylic acid
    [334] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) ethyl] piperidine-4- Carboxylic acid
    [335] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy) ethyl] piperidine- 4-carboxylic acid
    [336] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylthio) ethyl] piperidine- 4-carboxylic acid
    [337] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine-4-carboxylic acid
    [338] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl] piperidine-4-carboxylic acid
    [339] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] piperidine-4-carboxylic acid
    [340] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) prop-2-ynyl] Piperidine-4-carboxylic acid
    [341] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperidine-4 Carboxylic acid
    [342] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) propyl] piperidine-4-carboxylic acid
    [343] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) propyl] piperidine-4-carboxylic acid
    [344] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylthio) ethyl] piperidine-4-carboxylic acid
    [345] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylthio) ethyl] piperidine-4-carboxylic acid
    [346] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylamino) ethyl] piperidine-4-carboxylic acid
    [347] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylamino) ethyl] piperidine-4-carboxylic acid
    [348] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenoxy) ethyl] piperidine-4-carboxylic acid
    [349] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenoxy) ethyl] piperidine-4-carboxylic acid
    [350] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) prop-2-ynyl] piperidine 4-carboxylic acid
    [351] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) prop-2-ynyl] piperidine 4-carboxylic acid
    [352] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) propyl] piperidine-4-carboxylic acid
    [353] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) propyl] piperidine-4-carboxylic acid
    [354] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylthio) ethyl] -piperidine-4 Carboxylic acid
    [355] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylthio) ethyl] -piperidine-4 Carboxylic acid
    [356] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylamino) ethyl] -piperidine-4 Carboxylic acid
    [357] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylamino) ethyl] -piperidine-4 Carboxylic acid
    [358] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenoxy) ethyl] -piperidine-4 Carboxylic acid
    [359] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenoxy) ethyl] -piperidine-4 Carboxylic acid
    [360] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) prop-2-ynyl] piperi Dean-4-carboxylic acid
    [361] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) prop-2-ynyl] piperi Dean-4-carboxylic acid
    [362] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) -propyl] piperidine-4- Carboxylic acid
    [363] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) -propyl] piperidine-4- Carboxylic acid
    [364] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylthio) -ethyl] piperidine-4 Carboxylic acid
    [365] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylthio) -ethyl] piperidine-4 Carboxylic acid
    [366] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylamino) -ethyl] -piperidine- 4-carboxylic acid
    [367] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylamino) -ethyl] piperidine-4 Carboxylic acid
    [368] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenoxy) -ethyl] piperidine-4 Carboxylic acid
    [369] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenoxy) -ethyl] piperidine-4 Carboxylic acid
    [370] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) prop-2-ynyl] piperi Dean-4-carboxylic acid
    [371] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) prop-2-ynyl] piperi Dean-4-carboxylic acid
    [372] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) propyl] piperidine-4- Carboxylic acid
    [373] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylthio) ethyl] piperidine-4 Carboxylic acid
    [374] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylthio) ethyl] piperidine-4 Carboxylic acid
    [375] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylamino) ethyl] piperidine-4 Carboxylic acid
    [376] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylamino) ethyl] piperidine-4 Carboxylic acid
    [377] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenoxy) -ethyl] piperidine- 4-carboxylic acid
    [378] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenoxy) -ethyl] piperidine- 4-carboxylic acid
    [379] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) prop-2-ynyl] pi Ferridine-4-carboxylic acid
    [380] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) prop-2-ynyl] pi Ferridine-4-carboxylic acid
    [381] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) propyl] piperidine-4- Carboxylic acid
    [382] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) propyl] piperidine-4- Carboxylic acid
    [383] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylthio) ethyl] piperidine-4 Carboxylic acid
    [384] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylthio) ethyl] -piperidine- 4-carboxylic acid
    [385] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylamino) -ethyl] piperidine- 4-carboxylic acid
    [386] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylamino) -ethyl] piperidine- 4-carboxylic acid
    [387] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenoxy) -ethyl] piperidine- 4-carboxylic acid
    [388] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenoxy) -ethyl] piperidine- 4-carboxylic acid
    [389] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) prop-2-ynyl] pi Ferridine-4-carboxylic acid
    [390] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) prop-2-ynyl] pi Ferridine-4-carboxylic acid
    [391] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) propyl] piperidine-4-carboxylic acid
    [392] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) propyl] piperidine-4-carboxylic acid
    [393] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylthio) ethyl] piperidine-4- Carboxylic acid
    [394] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylthio) ethyl] piperidine-4- Carboxylic acid
    [395] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylamino) ethyl] piperidine-4- Carboxylic acid
    [396] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylamino) ethyl] piperidine-4- Carboxylic acid
    [397] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenoxy) ethyl] piperidine-4- Carboxylic acid
    [398] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenoxy) ethyl] piperidine-4- Carboxylic acid
    [399] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) prop-2-ynyl] piperi Dean-4-carboxylic acid
    [400] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) prop-2-ynyl] piperi Dean-4-carboxylic acid
    [401] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) -propyl] piperidine- 4-carboxylic acid
    [402] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) -propyl] piperidine- 4-carboxylic acid
    [403] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylthio) -ethyl] piperidine 4-carboxylic acid
    [404] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylthio) -ethyl] piperidine 4-carboxylic acid
    [405] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylamino) ethyl] piperidine- 4-carboxylic acid
    [406] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylamino) ethyl] piperidine- 4-carboxylic acid
    [407] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenoxy) -ethyl] piperidine 4-carboxylic acid
    [408] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenoxy) ethyl] piperidine- 4-carboxylic acid
    [409] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) -prop-2-ynyl ] Piperidine-4-carboxylic acid
    [410] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) -prop-2-ynyl ] Piperidine-4-carboxylic acid
    [411] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1-heptylpiperidine-4-carboxylic acid
    [412] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4-phenylbutyl] piperidine-4-carboxylic acid
    [413] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine-4- Carboxylic acid
    [414] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (2-fluorophenyl) propyl] piperi Dean-4-carboxylic acid
    [415] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (3-fluorophenyl) propyl] piperi Dean-4-carboxylic acid
    [416] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenyl) propyl] piperi Dean-4-carboxylic acid
    [417] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (4-fluorophenyl) butyl] piperi Dean-4-carboxylic acid
    [418] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenyl) propyl ] Piperidine-4-carboxylic acid
    [419] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (2,3-difluorophenyl) propyl ] Piperidine-4-carboxylic acid
    [420] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluorophenyl) propyl ] Piperidine-4-carboxylic acid
    [421] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (2,6-difluorophenyl) propyl ] Piperidine-4-carboxylic acid
    [422] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-difluorophenyl) propyl ] Piperidine-4-carboxylic acid
    [423] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl ) Propyl] piperidine-4-carboxylic acid
    [424] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3-phenylthio-propyl] piperidine-4- Carboxylic acid
    [425] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenylthio) propyl] py Ferridine-4-carboxylic acid
    [426] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenylthio) propyl] py Ferridine-4-carboxylic acid
    [427] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-fluorophenylthio) ethyl] py Ferridine-4-carboxylic acid
    [428] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenylthio) propyl] py Ferridine-4-carboxylic acid
    [429] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3-difluorophenylthio) Ethyl] piperidine-4-carboxylic acid
    [430] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenylthio) Propyl] piperidine-4-carboxylic acid
    [431] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,6-difluorophenylthio) Ethyl] piperidine-4-carboxylic acid
    [432] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenyl Thio) ethyl] piperidine-4-carboxylic acid
    [433] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenyl Thio) ethyl] piperidine-4-carboxylic acid
    [434] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenyl Thio) ethyl] piperidine-4-carboxylic acid
    [435] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) Ethyl] piperidine-4-carboxylic acid
    [436] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy Ethyl] piperidine-4-carboxylic acid
    [437] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenoxy Ethyl] piperidine-4-carboxylic acid
    [438] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenoxy Ethyl] piperidine-4-carboxylic acid
    [439] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino) Ethyl] piperidine-4-carboxylic acid
    [440] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenyl Amino) ethyl] piperidine-4-carboxylic acid
    [441] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenyl Amino) ethyl] piperidine-4-carboxylic acid
    [442] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenyl Amino) ethyl] piperidine-4-carboxylic acid
    [443] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluorophenylthio) Propyl] piperidine-4-carboxylic acid
    [444] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2-chlorophenylthio) ethyl] piperi Dean-4-carboxylic acid
    [445] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chlorophenylthio) propyl] piperi Dean-4-carboxylic acid
    [446] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3-chlorophenylthio) ethyl] piperi Dean-4-carboxylic acid
    [447] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorophenylthio) propyl] piperi Dean-4-carboxylic acid
    [448] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-chlorophenylthio) ethyl] piperi Dean-4-carboxylic acid
    [449] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chlorophenylthio) propyl] piperi Dean-4-carboxylic acid
    [450] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2-methylphenylthio) ethyl] piperidine 4-carboxylic acid
    [451] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methylphenylthio) propyl] piperidine 4-carboxylic acid
    [452] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methylphenylthio) ethyl] piperidine 4-carboxylic acid
    [453] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylphenylthio) propyl] piperidine 4-carboxylic acid
    [454] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-methylphenylthio) ethyl] piperidine 4-carboxylic acid
    [455] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methylphenylthio) propyl] piperidine 4-carboxylic acid
    [456] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2-trifluoromethylphenylthio) ethyl] Piperidine-4-carboxylic acid
    [457] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-trifluoromethylphenylthio) propyl] Piperidine-4-carboxylic acid
    [458] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3-trifluoromethylphenylthio) ethyl] Piperidine-4-carboxylic acid
    [459] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethylphenylthio) propyl] Piperidine-4-carboxylic acid
    [460] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-trifluoromethylphenylthio) ethyl] Piperidine-4-carboxylic acid
    [461] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-trifluoromethylphenylthio) propyl] Piperidine-4-carboxylic acid
    [462] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2-methoxyphenylthio) ethyl] py Ferridine-4-carboxylic acid
    [463] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxyphenylthio) propyl] py Ferridine-4-carboxylic acid
    [464] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methoxyphenylthio) ethyl] py Ferridine-4-carboxylic acid
    [465] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxyphenylthio) propyl] py Ferridine-4-carboxylic acid
    [466] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-methoxyphenylthio) ethyl] py Ferridine-4-carboxylic acid
    [467] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methoxyphenylthio) propyl] py Ferridine-4-carboxylic acid
    [468] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [cyclopentylmethyl] piperidine-4-carboxylic acid
    [469] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentyl) ethyl] piperidine-4 Carboxylic acid
    [470] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine-4 Carboxylic acid
    [471] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine- 4-carboxylic acid
    [472] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclopentylthio) propyl] piperidine- 4-carboxylic acid
    [473] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclohexylthio) propyl] piperidine- 4-carboxylic acid
    [474] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl] Piperidine-4-carboxylic acid
    [475] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (thien-2-yl) butyl] piperi Dean-4-carboxylic acid
    [476] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) thiopropyl] py Ferridine-4-carboxylic acid
    [477] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) propyl] piperi Dean-4-carboxylic acid
    [478] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (thien-3-yl) butyl] piperi Dean-4-carboxylic acid
    [479] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] py Ferridine-4-carboxylic acid
    [480] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-3-yl) thioethyl] py Ferridine-4-carboxylic acid
    [481] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) thiopropyl] py Ferridine-4-carboxylic acid
    [482] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-2-yl ) Propyl] piperidine-4-carboxylic acid
    [483] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (1,3-thiazol-2-yl ) Butyl] piperidine-4-carboxylic acid
    [484] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-2-yl ) Thioethyl] piperidine-4-carboxylic acid
    [485] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-2-yl) propyl] py Ferridine-4-carboxylic acid
    [486] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrid-2-yl) butyl] pi Ferridine-4-carboxylic acid
    [487] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-2-yl) thiopropyl] Piperidine-4-carboxylic acid
    [488] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-3-yl) propyl] py Ferridine-4-carboxylic acid
    [489] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrid-3-yl) butyl] pi Ferridine-4-carboxylic acid
    [490] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-3-yl) thioethyl] Piperidine-4-carboxylic acid
    [491] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-3-yl) thiopropyl] Piperidine-4-carboxylic acid
    [492] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-4-yl) propyl] py Ferridine-4-carboxylic acid
    [493] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrid-4-yl) butyl] pi Ferridine-4-carboxylic acid
    [494] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-4-yl) thioethyl] Piperidine-4-carboxylic acid
    [495] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-4-yl) thiopropyl] Piperidine-4-carboxylic acid
    [496] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) propyl] piperi Dean-4-carboxylic acid
    [497] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrazin-2-yl) butyl] piperi Dean-4-carboxylic acid
    [498] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrazin-2-yl) thioethyl] py Ferridine-4-carboxylic acid
    [499] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) thiopropyl] py Ferridine-4-carboxylic acid
    [500] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenyl) prop-2 -Inyl] piperidine-4-carboxylic acid
    [501] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4-difluorophenyl) prop Ph-2-ynyl] piperidine-4-carboxylic acid
    [502] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4-difluorophenyl) prop Ph-2-ynyl] piperidine-4-carboxylic acid
    [503] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl ) Prop-2-ynyl] piperidine-4-carboxylic acid
    [504] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl ) Prop-2-ynyl] piperidine-4-carboxylic acid
    [505] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl ) Prop-2-ynyl] piperidine-4-carboxylic acid
    [506] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-3-fluorophenyl) Prop-2-ynyl] piperidine-4-carboxylic acid
    [507] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-4-fluorophenyl) Prop-2-ynyl] piperidine-4-carboxylic acid
    [508] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-4-fluorophenyl) Prop-2-ynyl] piperidine-4-carboxylic acid
    [509] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-5-fluorophenyl) Prop-2-ynyl] piperidine-4-carboxylic acid
    [510] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-2-fluorophenyl) Prop-2-ynyl] piperidine-4-carboxylic acid
    [511] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluoro-4-methylphenyl) prop Ph-2-ynyl] piperidine-4-carboxylic acid
    [512] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-bis (trifluoromethyl ) Phenyl) prop-2-ynyl] piperidine-4-carboxylic acid
    [513] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2 -Inyl] piperidine-4-carboxylic acid
    [514] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) prop-2 -Inyl] piperidine-4-carboxylic acid
    [515] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-2-yl ) Prop-2-ynyl] piperidine-4-carboxylic acid
    [516] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-4-yl ) Prop-2-ynyl] piperidine-4-carboxylic acid
    [517] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-5-yl ) Prop-2-ynyl] piperidine-4-carboxylic acid
    [518] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-2-yl) prop- 2-ynyl] piperidine-4-carboxylic acid
    [519] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-3-yl) prop- 2-ynyl] piperidine-4-carboxylic acid
    [520] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-4-yl) prop- 2-ynyl] piperidine-4-carboxylic acid
    [521] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine-4 Carboxylic acid
    [522] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine-4- Carboxylic acid
    [523] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl ) Propyl] piperidine-4-carboxylic acid
    [524] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino) Ethyl] piperidine-4-carboxylic acid
    [525] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenyl Amino) ethyl] piperidine-4-carboxylic acid
    [526] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) Ethyl] piperidine-4-carboxylic acid
    [527] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy Ethyl] piperidine-4-carboxylic acid
    [528] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenyl Thio) ethyl] piperidine-4-carboxylic acid
    [529] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine- 4-carboxylic acid
    [530] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl] Piperidine-4-carboxylic acid
    [531] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] py Ferridine-4-carboxylic acid
    [532] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl ) Prop-2-ynyl] piperidine-4-carboxylic acid
    [533] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2 -Inyl] piperidine-4-carboxylic acid
    [534] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine- 4-carboxylic acid
    [535] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine-4 Carboxylic acid
    [536] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Phenyl) propyl] piperidine-4-carboxylic acid
    [537] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino Ethyl] piperidine-4-carboxylic acid
    [538] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenylamino) ethyl] piperidine-4-carboxylic acid
    [539] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenoxy) ethyl] piperidine-4-carboxylic acid
    [540] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenylthio) ethyl] piperidine-4-carboxylic acid
    [541] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine 4-carboxylic acid
    [542] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl ] Piperidine-4-carboxylic acid
    [543] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] Piperidine-4-carboxylic acid
    [544] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Phenyl) prop-2-ynyl] piperidine-4-carboxylic acid
    [545] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop- 2-ynyl] piperidine-4-carboxylic acid
    [546] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine- 4-carboxylic acid
    [547] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine-4 Carboxylic acid
    [548] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Phenyl) propyl] piperidine-4-carboxylic acid
    [549] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino Ethyl] piperidine-4-carboxylic acid
    [550] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenylamino) ethyl] piperidine-4-carboxylic acid
    [551] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy Ethyl] piperidine-4-carboxylic acid
    [552] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenoxy) ethyl] piperidine-4-carboxylic acid
    [553] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenylthio) ethyl] piperidine-4-carboxylic acid
    [554] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine 4-carboxylic acid
    [555] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl ] Piperidine-4-carboxylic acid
    [556] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] Piperidine-4-carboxylic acid
    [557] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Phenyl) prop-2-ynyl] piperidine-4-carboxylic acid
    [558] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop- 2-ynyl] piperidine-4-carboxylic acid
    [559] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine 4-carboxylic acid
    [560] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine- 4-carboxylic acid
    [561] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Rophenyl) propyl] piperidine-4-carboxylic acid
    [562] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenyl Amino) ethyl] piperidine-4-carboxylic acid
    [563] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Rophenylamino) ethyl] piperidine-4-carboxylic acid
    [564] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy Ethyl] piperidine-4-carboxylic acid
    [565] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Rophenoxy) ethyl] piperidine-4-carboxylic acid
    [566] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Rophenylthio) ethyl] piperidine-4-carboxylic acid
    [567] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperi Dean-4-carboxylic acid
    [568] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thio Ethyl] piperidine-4-carboxylic acid
    [569] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl ] Piperidine-4-carboxylic acid
    [570] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Rophenyl) prop-2-ynyl] piperidine-4-carboxylic acid
    [571] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop -2-ynyl] piperidine-4-carboxylic acid
    [572] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine 4-carboxylic acid
    [573] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine- 4-carboxylic acid
    [574] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Rophenyl) propyl] piperidine-4-carboxylic acid
    [575] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenyl Amino) ethyl] piperidine-4-carboxylic acid
    [576] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Rophenylamino) ethyl] piperidine-4-carboxylic acid
    [577] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy Ethyl] piperidine-4-carboxylic acid
    [578] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Rophenoxy) ethyl] piperidine-4-carboxylic acid
    [579] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Rophenylthio) ethyl] piperidine-4-carboxylic acid
    [580] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperi Dean-4-carboxylic acid
    [581] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thio Ethyl] piperidine-4-carboxylic acid
    [582] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl ] Piperidine-4-carboxylic acid
    [583] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Rophenyl) prop-2-ynyl] piperidine-4-carboxylic acid
    [584] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop -2-ynyl] piperidine-4-carboxylic acid
    [585] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine- 4-carboxylic acid
    [586] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine-4 Carboxylic acid
    [587] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Phenyl) propyl] piperidine-4-carboxylic acid
    [588] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino Ethyl] piperidine-4-carboxylic acid
    [589] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenylamino) ethyl] piperidine-4-carboxylic acid
    [590] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy Ethyl] piperidine-4-carboxylic acid
    [591] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenoxy) ethyl] piperidine-4-carboxylic acid
    [592] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenylthio) ethyl] piperidine-4-carboxylic acid
    [593] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine 4-carboxylic acid
    [594] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl ] Piperidine-4-carboxylic acid
    [595] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] Piperidine-4-carboxylic acid
    [596] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Phenyl) prop-2-ynyl] piperidine-4-carboxylic acid
    [597] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop- 2-ynyl] piperidine-4-carboxylic acid
    [598] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperi Dean-4-carboxylic acid
    [599] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine 4-carboxylic acid
    [600] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-tri Fluorophenyl) propyl] piperidine-4-carboxylic acid
    [601] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluoro Phenylamino) ethyl] piperidine-4-carboxylic acid
    [602] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-tri Fluorophenylamino) ethyl] piperidine-4-carboxylic acid
    [603] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluoro Phenoxy) ethyl] piperidine-4-carboxylic acid
    [604] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-tri Fluorophenoxy) ethyl] piperidine-4-carboxylic acid
    [605] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-tri Fluorophenylthio) ethyl] piperidine-4-carboxylic acid
    [606] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] py Ferridine-4-carboxylic acid
    [607] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) Thioethyl] piperidine-4-carboxylic acid
    [608] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thio Ethyl] piperidine-4-carboxylic acid
    [609] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-tri Fluorophenyl) prop-2-ynyl] piperidine-4-carboxylic acid
    [610] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) pro Ph-2-ynyl] piperidine-4-carboxylic acid
    [611] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl ) Propyl] piperidine-4-carboxylic acid
    [612] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl ) Propyl] piperidine-4-carboxylic acid
    [613] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenyl Thio) ethyl] piperidine-4-carboxylic acid
    [614] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenyl Thio) ethyl] piperidine-4-carboxylic acid
    [615] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenyl Amino) ethyl] piperidine-4-carboxylic acid
    [616] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenyl Amino) ethyl] piperidine-4-carboxylic acid
    [617] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenoxy Ethyl] piperidine-4-carboxylic acid
    [618] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenoxy Ethyl] piperidine-4-carboxylic acid
    [619] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl ) Prop-2-ynyl] piperidine-4-carboxylic acid
    [620] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl ) Prop-2-ynyl] piperidine-4-carboxylic acid
    [621] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) propyl] piperidine-4-carboxylic acid
    [622] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Phenyl) propyl] piperidine-4-carboxylic acid
    [623] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenylthio) ethyl] piperidine-4-carboxylic acid
    [624] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenylthio) ethyl] piperidine-4-carboxylic acid
    [625] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenylamino) ethyl] piperidine-4-carboxylic acid
    [626] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenylamino) ethyl] piperidine-4-carboxylic acid
    [627] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenoxy) ethyl] piperidine-4-carboxylic acid
    [628] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenoxy) ethyl] piperidine-4-carboxylic acid
    [629] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) prop-2-ynyl] piperidine-4-carboxylic acid
    [630] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Phenyl) prop-2-ynyl] piperidine-4-carboxylic acid
    [631] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) propyl] piperidine-4-carboxylic acid
    [632] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Phenyl) propyl] piperidine-4-carboxylic acid
    [633] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenylthio) ethyl] piperidine-4-carboxylic acid
    [634] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenylthio) ethyl] piperidine-4-carboxylic acid
    [635] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenylamino) ethyl] piperidine-4-carboxylic acid
    [636] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenylamino) ethyl] piperidine-4-carboxylic acid
    [637] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenoxy) ethyl] piperidine-4-carboxylic acid
    [638] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenoxy) ethyl] piperidine-4-carboxylic acid
    [639] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) prop-2-ynyl] piperidine-4-carboxylic acid
    [640] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Phenyl) prop-2-ynyl] piperidine-4-carboxylic acid
    [641] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Rophenyl) propyl] piperidine-4-carboxylic acid
    [642] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Rophenylthio) ethyl] piperidine-4-carboxylic acid
    [643] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Rophenylthio) ethyl] piperidine-4-carboxylic acid
    [644] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Rophenylamino) ethyl] piperidine-4-carboxylic acid
    [645] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Rophenylamino) ethyl] piperidine-4-carboxylic acid
    [646] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Rophenoxy) ethyl] piperidine-4-carboxylic acid
    [647] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Rophenoxy) ethyl] piperidine-4-carboxylic acid
    [648] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Rophenyl) prop-2-ynyl] piperidine-4-carboxylic acid
    [649] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Rophenyl) prop-2-ynyl] piperidine-4-carboxylic acid
    [650] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Rophenyl) propyl] piperidine-4-carboxylic acid
    [651] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Rophenyl) propyl] piperidine-4-carboxylic acid
    [652] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Rophenylthio) ethyl] piperidine-4-carboxylic acid
    [653] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Rophenylthio) ethyl] piperidine-4-carboxylic acid
    [654] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Rophenylamino) ethyl] piperidine-4-carboxylic acid
    [655] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Rophenylamino) ethyl] piperidine-4-carboxylic acid
    [656] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Rophenoxy) ethyl] piperidine-4-carboxylic acid
    [657] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Rophenoxy) ethyl] piperidine-4-carboxylic acid
    [658] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Rophenyl) prop-2-ynyl] piperidine-4-carboxylic acid
    [659] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Rophenyl) prop-2-ynyl] piperidine-4-carboxylic acid
    [660] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) propyl] piperidine-4-carboxylic acid
    [661] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Phenyl) propyl] piperidine-4-carboxylic acid
    [662] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenylthio) ethyl] piperidine-4-carboxylic acid
    [663] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenylthio) ethyl] piperidine-4-carboxylic acid
    [664] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenylamino) ethyl] piperidine-4-carboxylic acid
    [665] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenylamino) ethyl] piperidine-4-carboxylic acid
    [666] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenoxy) ethyl] piperidine-4-carboxylic acid
    [667] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenoxy) ethyl] piperidine-4-carboxylic acid
    [668] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) prop-2-ynyl] piperidine-4-carboxylic acid
    [669] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Phenyl) prop-2-ynyl] piperidine-4-carboxylic acid
    [670] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-tri Fluorophenyl) propyl] piperidine-4-carboxylic acid
    [671] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-tri Fluorophenyl) propyl] piperidine-4-carboxylic acid
    [672] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-tri Fluorophenylthio) ethyl] piperidine-4-carboxylic acid
    [673] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-tri Fluorophenylthio) ethyl] piperidine-4-carboxylic acid
    [674] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-tri Fluorophenylamino) ethyl] piperidine-4-carboxylic acid
    [675] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-tri Fluorophenylamino) ethyl] piperidine-4-carboxylic acid
    [676] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-tri Fluorophenoxy) ethyl] piperidine-4-carboxylic acid
    [677] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-tri Fluorophenoxy) ethyl] piperidine-4-carboxylic acid
    [678] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-tri Fluorophenyl) prop-2-ynyl] piperidine-4-carboxylic acid
    [679] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-tri Fluorophenyl) prop-2-ynyl] piperidine-4-carboxylic acid
    [680] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1-heptylpiperidine-4-carboxylic acid
    [681] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4-phenylbutyl] piperidine-4-carboxylic acid
    [682] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine-4- Carboxylic acid
    [683] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (2-fluorophenyl) propyl] piperi Dean-4-carboxylic acid
    [684] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (3-fluorophenyl) propyl] piperi Dean-4-carboxylic acid
    [685] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenyl) propyl] piperi Dean-4-carboxylic acid
    [686] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (4-fluorophenyl) butyl] piperi Dean-4-carboxylic acid
    [687] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenyl) propyl ] Piperidine-4-carboxylic acid
    [688] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (2,3-difluorophenyl) propyl ] Piperidine-4-carboxylic acid
    [689] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluorophenyl) propyl ] Piperidine-4-carboxylic acid
    [690] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (2,6-difluorophenyl) propyl ] Piperidine-4-carboxylic acid
    [691] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-difluorophenyl) propyl ] Piperidine-4-carboxylic acid
    [692] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl ) Propyl] piperidine-4-carboxylic acid
    [693] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl ) Propyl] piperidine-4-carboxylic acid
    [694] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl ) Propyl] piperidine-4-carboxylic acid
    [695] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3-phenylthio-propyl] piperidine-4- Carboxylic acid
    [696] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenylthio) propyl] py Ferridine-4-carboxylic acid
    [697] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenylthio) propyl] py Ferridine-4-carboxylic acid
    [698] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-fluorophenylthio) ethyl] py Ferridine-4-carboxylic acid
    [699] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenylthio) propyl] py Ferridine-4-carboxylic acid
    [700] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3-difluorophenylthio) Ethyl] piperidine-4-carboxylic acid
    [701] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenylthio) Propyl] piperidine-4-carboxylic acid
    [702] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,6-difluorophenylthio) Ethyl] piperidine-4-carboxylic acid
    [703] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenyl Thio) ethyl] piperidine-4-carboxylic acid
    [704] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenyl Thio) ethyl] piperidine-4-carboxylic acid
    [705] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenyl Thio) ethyl] piperidine-4-carboxylic acid
    [706] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy Ethyl] piperidine-4-carboxylic acid
    [707] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenoxy Ethyl] piperidine-4-carboxylic acid
    [708] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenoxy Ethyl] piperidine-4-carboxylic acid
    [709] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino) Ethyl] piperidine-4-carboxylic acid
    [710] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenyl Amino) ethyl] piperidine-4-carboxylic acid
    [711] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenyl Amino) ethyl] piperidine-4-carboxylic acid
    [712] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenyl Amino) ethyl] piperidine-4-carboxylic acid
    [713] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluorophenylthio) Propyl] piperidine-4-carboxylic acid
    [714] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2-chlorophenylthio) ethyl] piperi Dean-4-carboxylic acid
    [715] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chlorophenylthio) propyl] piperi Dean-4-carboxylic acid
    [716] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3-chlorophenylthio) ethyl] piperi Dean-4-carboxylic acid
    [717] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorophenylthio) propyl] piperi Dean-4-carboxylic acid
    [718] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-chlorophenylthio) ethyl] piperi Dean-4-carboxylic acid
    [719] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chlorophenylthio) propyl] piperi Dean-4-carboxylic acid
    [720] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2-methylphenylthio) ethyl] piperidine 4-carboxylic acid
    [721] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methylphenylthio) propyl] piperidine 4-carboxylic acid
    [722] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methylphenylthio) ethyl] piperidine 4-carboxylic acid
    [723] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylphenylthio) propyl] piperidine 4-carboxylic acid
    [724] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-methylphenylthio) ethyl] piperidine 4-carboxylic acid
    [725] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methylphenylthio) propyl] piperidine 4-carboxylic acid
    [726] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2-trifluoromethylphenylthio) ethyl] Piperidine-4-carboxylic acid
    [727] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-trifluoromethylphenylthio) propyl] Piperidine-4-carboxylic acid
    [728] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3-trifluoromethylphenylthio) ethyl] Piperidine-4-carboxylic acid
    [729] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethylphenylthio) propyl] Piperidine-4-carboxylic acid
    [730] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-trifluoromethylphenylthio) ethyl] Piperidine-4-carboxylic acid
    [731] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-trifluoromethylphenylthio) propyl] Piperidine-4-carboxylic acid
    [732] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2-methoxyphenylthio) ethyl] py Ferridine-4-carboxylic acid
    [733] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxyphenylthio) propyl] py Ferridine-4-carboxylic acid
    [734] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methoxyphenylthio) ethyl] py Ferridine-4-carboxylic acid
    [735] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxyphenylthio) propyl] py Ferridine-4-carboxylic acid
    [736] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-methoxyphenylthio) ethyl] py Ferridine-4-carboxylic acid
    [737] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methoxyphenylthio) propyl] py Ferridine-4-carboxylic acid
    [738] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [cyclopentylmethyl] piperidine-4-carboxylic acid
    [739] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentyl) ethyl] piperidine-4 Carboxylic acid
    [740] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine-4 Carboxylic acid
    [741] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine- 4-carboxylic acid
    [742] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclopentylthio) propyl] piperidine- 4-carboxylic acid
    [743] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclohexylthio) propyl] piperidine- 4-carboxylic acid
    [744] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl] Piperidine-4-carboxylic acid
    [745] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (thien-2-yl) butyl] piperi Dean-4-carboxylic acid
    [746] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) thiopropyl] py Ferridine-4-carboxylic acid
    [747] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) propyl] piperi Dean-4-carboxylic acid
    [748] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (thien-3-yl) butyl] piperi Dean-4-carboxylic acid
    [749] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] py Ferridine-4-carboxylic acid
    [750] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-3-yl) thioethyl] py Ferridine-4-carboxylic acid
    [751] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) thiopropyl] py Ferridine-4-carboxylic acid
    [752] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-2-yl ) Propyl] piperidine-4-carboxylic acid
    [753] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (1,3-thiazol-2-yl ) Butyl] piperidine-4-carboxylic acid
    [754] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-2-yl ) Thioethyl] piperidine-4-carboxylic acid
    [755] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-2-yl) propyl] py Ferridine-4-carboxylic acid
    [756] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrid-2-yl) butyl] pi Ferridine-4-carboxylic acid
    [757] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-2-yl) thiopropyl] Piperidine-4-carboxylic acid
    [758] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-3-yl) propyl] py Ferridine-4-carboxylic acid
    [759] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrid-3-yl) butyl] pi Ferridine-4-carboxylic acid
    [760] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-3-yl) thioethyl] Piperidine-4-carboxylic acid
    [761] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-3-yl) thiopropyl] Piperidine-4-carboxylic acid
    [762] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-4-yl) propyl] py Ferridine-4-carboxylic acid
    [763] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrid-4-yl) butyl] pi Ferridine-4-carboxylic acid
    [764] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-4-yl) thioethyl] Piperidine-4-carboxylic acid
    [765] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-4-yl) thiopropyl] Piperidine-4-carboxylic acid
    [766] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) propyl] piperi Dean-4-carboxylic acid
    [767] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrazin-2-yl) butyl] piperi Dean-4-carboxylic acid
    [768] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrazin-2-yl) thioethyl] py Ferridine-4-carboxylic acid
    [769] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) thiopropyl] py Ferridine-4-carboxylic acid
    [770] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenyl) prop-2 -Inyl] piperidine-4-carboxylic acid
    [771] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4-difluorophenyl) prop Ph-2-ynyl] piperidine-4-carboxylic acid
    [772] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4-difluorophenyl) prop Ph-2-ynyl] piperidine-4-carboxylic acid
    [773] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl ) Prop-2-ynyl] piperidine-4-carboxylic acid
    [774] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl ) Prop-2-ynyl] piperidine-4-carboxylic acid
    [775] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl ) Prop-2-ynyl] piperidine-4-carboxylic acid
    [776] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-3-fluorophenyl) Prop-2-ynyl] piperidine-4-carboxylic acid
    [777] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-4-fluorophenyl) Prop-2-ynyl] piperidine-4-carboxylic acid
    [778] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-4-fluorophenyl) Prop-2-ynyl] piperidine-4-carboxylic acid
    [779] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-5-fluorophenyl) Prop-2-ynyl] piperidine-4-carboxylic acid
    [780] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-2-fluorophenyl) Prop-2-ynyl] piperidine-4-carboxylic acid
    [781] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluoro-4-methylphenyl) prop Ph-2-ynyl] piperidine-4-carboxylic acid
    [782] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-bis (trifluoromethyl ) Phenyl) prop-2-ynyl] piperidine-4-carboxylic acid
    [783] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2 -Inyl] piperidine-4-carboxylic acid
    [784] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) prop-2 -Inyl] piperidine-4-carboxylic acid
    [785] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-2-yl ) Prop-2-ynyl] piperidine-4-carboxylic acid
    [786] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-4-yl ) Prop-2-ynyl] piperidine-4-carboxylic acid
    [787] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-5-yl ) Prop-2-ynyl] piperidine-4-carboxylic acid
    [788] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-2-yl) prop- 2-ynyl] piperidine-4-carboxylic acid
    [789] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-3-yl) prop- 2-ynyl] piperidine-4-carboxylic acid
    [790] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-4-yl) prop- 2-ynyl] piperidine-4-carboxylic acid
    [791] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine-4 Carboxylic acid
    [792] 4- [3- (R, S) -fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine-4- Carboxylic acid
    [793] 4- [3- (R, S) -fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl ) Propyl] piperidine-4-carboxylic acid
    [794] 4- [3- (R, S) -fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino) Ethyl] piperidine-4-carboxylic acid
    [795] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenyl Amino) ethyl] piperidine-4-carboxylic acid
    [796] 4- [3- (R, S) -fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) Ethyl] piperidine-4-carboxylic acid
    [797] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy Ethyl] piperidine-4-carboxylic acid
    [798] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenyl Thio) ethyl] piperidine-4-carboxylic acid
    [799] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine- 4-carboxylic acid
    [800] 4- [3- (R, S) -fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl] Piperidine-4-carboxylic acid
    [801] 4- [3- (R, S) -fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] py Ferridine-4-carboxylic acid
    [802] 4- [3- (R, S) -fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl ) Prop-2-ynyl] piperidine-4-carboxylic acid
    [803] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2 -Inyl] piperidine-4-carboxylic acid
    [804] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine- 4-carboxylic acid
    [805] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine-4 Carboxylic acid
    [806] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Phenyl) propyl] piperidine-4-carboxylic acid
    [807] 4- [3- (R, S) -fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino Ethyl] piperidine-4-carboxylic acid
    [808] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenylamino) ethyl] piperidine-4-carboxylic acid
    [809] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy Ethyl] piperidine-4-carboxylic acid
    [810] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenoxy) ethyl] piperidine-4-carboxylic acid
    [811] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenylthio) ethyl] piperidine-4-carboxylic acid
    [812] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine 4-carboxylic acid
    [813] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl ] Piperidine-4-carboxylic acid
    [814] 4- [3- (R, S) -fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] Piperidine-4-carboxylic acid
    [815] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Phenyl) prop-2-ynyl] piperidine-4-carboxylic acid
    [816] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop- 2-ynyl] piperidine-4-carboxylic acid
    [817] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine- 4-carboxylic acid
    [818] 4- [3- (R, S) -fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine-4 Carboxylic acid
    [819] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Phenyl) propyl] piperidine-4-carboxylic acid
    [820] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino Ethyl] piperidine-4-carboxylic acid
    [821] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenylamino) ethyl] piperidine-4-carboxylic acid
    [822] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy Ethyl] piperidine-4-carboxylic acid
    [823] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenoxy) ethyl] piperidine-4-carboxylic acid
    [824] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenylthio) ethyl] piperidine-4-carboxylic acid
    [825] 4- [3- (R, S) -fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine 4-carboxylic acid
    [826] 4- [3- (R, S) -fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl ] Piperidine-4-carboxylic acid
    [827] 4- [3- (R, S) -fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] Piperidine-4-carboxylic acid
    [828] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Phenyl) prop-2-ynyl] piperidine-4-carboxylic acid
    [829] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop- 2-ynyl] piperidine-4-carboxylic acid
    [830] 4- [3- (R, S) -fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine 4-carboxylic acid
    [831] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine- 4-carboxylic acid
    [832] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Rophenyl) propyl] piperidine-4-carboxylic acid
    [833] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenyl Amino) ethyl] piperidine-4-carboxylic acid
    [834] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Rophenylamino) ethyl] piperidine-4-carboxylic acid
    [835] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy Ethyl] piperidine-4-carboxylic acid
    [836] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Rophenoxy) ethyl] piperidine-4-carboxylic acid
    [837] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Rophenylthio) ethyl] piperidine-4-carboxylic acid
    [838] 4- [3- (R, S) -fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperi Dean-4-carboxylic acid
    [839] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thio Ethyl] piperidine-4-carboxylic acid
    [840] 4- [3- (R, S) -fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl ] Piperidine-4-carboxylic acid
    [841] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Rophenyl) prop-2-ynyl] piperidine-4-carboxylic acid
    [842] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop -2-ynyl] piperidine-4-carboxylic acid
    [843] 4- [3- (R, S) -fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine 4-carboxylic acid
    [844] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine- 4-carboxylic acid
    [845] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Rophenyl) propyl] piperidine-4-carboxylic acid
    [846] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenyl Amino) ethyl] piperidine-4-carboxylic acid
    [847] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Rophenylamino) ethyl] piperidine-4-carboxylic acid
    [848] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy Ethyl] piperidine-4-carboxylic acid
    [849] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Rophenoxy) ethyl] piperidine-4-carboxylic acid
    [850] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Rophenylthio) ethyl] piperidine-4-carboxylic acid
    [851] 4- [3- (R, S) -fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperi Dean-4-carboxylic acid
    [852] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thio Ethyl] piperidine-4-carboxylic acid
    [853] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl ] Piperidine-4-carboxylic acid
    [854] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Rophenyl) prop-2-ynyl] piperidine-4-carboxylic acid
    [855] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop -2-ynyl] piperidine-4-carboxylic acid
    [856] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine- 4-carboxylic acid
    [857] 4- [3- (R, S) -fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine-4 Carboxylic acid
    [858] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Phenyl) propyl] piperidine-4-carboxylic acid
    [859] 4- [3- (R, S) -fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino Ethyl] piperidine-4-carboxylic acid
    [860] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenylamino) ethyl] piperidine-4-carboxylic acid
    [861] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy Ethyl] piperidine-4-carboxylic acid
    [862] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenoxy) ethyl] piperidine-4-carboxylic acid
    [863] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenylthio) ethyl] piperidine-4-carboxylic acid
    [864] 4- [3- (R, S) -fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine 4-carboxylic acid
    [865] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl ] Piperidine-4-carboxylic acid
    [866] 4- [3- (R, S) -fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] Piperidine-4-carboxylic acid
    [867] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Phenyl) prop-2-ynyl] piperidine-4-carboxylic acid
    [868] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop- 2-ynyl] piperidine-4-carboxylic acid
    [869] 4- [3- (R, S) -fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperi Dean-4-carboxylic acid
    [870] 4- [3- (R, S) -fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine 4-carboxylic acid
    [871] 4- [3- (R, S) -fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-tri Fluorophenyl) propyl] piperidine-4-carboxylic acid
    [872] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluoro Phenylamino) ethyl] piperidine-4-carboxylic acid
    [873] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-tri Fluorophenylamino) ethyl] piperidine-4-carboxylic acid
    [874] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluoro Phenoxy) ethyl] piperidine-4-carboxylic acid
    [875] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-tri Fluorophenoxy) ethyl] piperidine-4-carboxylic acid
    [876] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-tri Fluorophenylthio) ethyl] piperidine-4-carboxylic acid
    [877] 4- [3- (R, S) -fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] py Ferridine-4-carboxylic acid
    [878] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) Thioethyl] piperidine-4-carboxylic acid
    [879] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thio Ethyl] piperidine-4-carboxylic acid
    [880] 4- [3- (R, S) -fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-tri Fluorophenyl) prop-2-ynyl] piperidine-4-carboxylic acid
    [881] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop Ph-2-ynyl] piperidine-4-carboxylic acid
    [882] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl ) Propyl] piperidine-4-carboxylic acid
    [883] 4- [3- (R, S) -fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl ) Propyl] piperidine-4-carboxylic acid
    [884] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenyl Thio) ethyl] piperidine-4-carboxylic acid
    [885] 4- [3- (R, S) -fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenyl Thio) ethyl] piperidine-4-carboxylic acid
    [886] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenyl Amino) ethyl] piperidine-4-carboxylic acid
    [887] 4- [3- (R, S) -fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenyl Amino) ethyl] piperidine-4-carboxylic acid
    [888] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenoxy Ethyl] piperidine-4-carboxylic acid
    [889] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenoxy Ethyl] piperidine-4-carboxylic acid
    [890] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl ) Prop-2-ynyl] piperidine-4-carboxylic acid
    [891] 4- [3- (R, S) -fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl ) Prop-2-ynyl] piperidine-4-carboxylic acid
    [892] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) propyl] piperidine-4-carboxylic acid
    [893] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Phenyl) propyl] piperidine-4-carboxylic acid
    [894] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenylthio) ethyl] piperidine-4-carboxylic acid
    [895] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenylthio) ethyl] piperidine-4-carboxylic acid
    [896] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenylamino) ethyl] piperidine-4-carboxylic acid
    [897] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenylamino) ethyl] piperidine-4-carboxylic acid
    [898] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenoxy) ethyl] piperidine-4-carboxylic acid
    [899] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenoxy) ethyl] piperidine-4-carboxylic acid
    [900] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) prop-2-ynyl] piperidine-4-carboxylic acid
    [901] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Phenyl) prop-2-ynyl] piperidine-4-carboxylic acid
    [902] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) propyl] piperidine-4-carboxylic acid
    [903] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Phenyl) propyl] piperidine-4-carboxylic acid
    [904] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenylthio) ethyl] piperidine-4-carboxylic acid
    [905] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenylthio) ethyl] piperidine-4-carboxylic acid
    [906] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenylamino) ethyl] piperidine-4-carboxylic acid
    [907] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenylamino) ethyl] piperidine-4-carboxylic acid
    [908] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenoxy) ethyl] piperidine-4-carboxylic acid
    [909] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenoxy) ethyl] piperidine-4-carboxylic acid
    [910] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) prop-2-ynyl] piperidine-4-carboxylic acid
    [911] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Phenyl) prop-2-ynyl] piperidine-4-carboxylic acid
    [912] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) propyl] piperidine-4-carboxylic acid
    [913] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl]
    [914] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Rophenylthio) ethyl] piperidine-4-carboxylic acid
    [915] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Rophenylthio) ethyl] piperidine-4-carboxylic acid
    [916] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Rophenylamino) ethyl] piperidine-4-carboxylic acid
    [917] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Rophenylamino) ethyl] piperidine-4-carboxylic acid
    [918] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Rophenoxy) ethyl] piperidine-4-carboxylic acid
    [919] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Rophenoxy) ethyl] piperidine-4-carboxylic acid
    [920] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Rophenyl) prop-2-ynyl] piperidine-4-carboxylic acid
    [921] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Rophenyl) prop-2-ynyl] piperidine-4-carboxylic acid
    [922] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Rophenyl) propyl] piperidine-4-carboxylic acid
    [923] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Rophenyl) propyl] piperidine-4-carboxylic acid
    [924] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Rophenylthio) ethyl] piperidine-4-carboxylic acid
    [925] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Rophenylthio) ethyl] piperidine-4-carboxylic acid
    [926] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Rophenylamino) ethyl] piperidine-4-carboxylic acid
    [927] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Rophenylamino) ethyl] piperidine-4-carboxylic acid
    [928] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Rophenoxy) ethyl] piperidine-4-carboxylic acid
    [929] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Rophenoxy) ethyl] piperidine-4-carboxylic acid
    [930] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Rophenyl) prop-2-ynyl] piperidine-4-carboxylic acid
    [931] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Rophenyl) prop-2-ynyl] piperidine-4-carboxylic acid
    [932] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) propyl] piperidine-4-carboxylic acid
    [933] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Phenyl) propyl] piperidine-4-carboxylic acid
    [934] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenylthio) ethyl] piperidine-4-carboxylic acid
    [935] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenylthio) ethyl] piperidine-4-carboxylic acid
    [936] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenylamino) ethyl] piperidine-4-carboxylic acid
    [937] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenylamino) ethyl] piperidine-4-carboxylic acid
    [938] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenoxy) ethyl] piperidine-4-carboxylic acid
    [939] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenoxy) ethyl] piperidine-4-carboxylic acid
    [940] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) prop-2-ynyl] piperidine-4-carboxylic acid
    [941] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Phenyl) prop-2-ynyl] piperidine-4-carboxylic acid
    [942] 4- [3- (R, S) -fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-tri Fluorophenyl) propyl] piperidine-4-carboxylic acid
    [943] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-tri Fluorophenyl) propyl] piperidine-4-carboxylic acid
    [944] 4- [3- (R, S) -fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-tri Fluorophenylthio) ethyl] piperidine-4-carboxylic acid
    [945] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-tri Fluorophenylthio) ethyl] piperidine-4-carboxylic acid
    [946] 4- [3- (R, S) -fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-tri Fluorophenylamino) ethyl] piperidine-4-carboxylic acid
    [947] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-tri Fluorophenylamino) ethyl] piperidine-4-carboxylic acid
    [948] 4- [3- (R, S) -fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-tri Fluorophenoxy) ethyl] piperidine-4-carboxylic acid
    [949] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-tri Fluorophenoxy) ethyl] piperidine-4-carboxylic acid
    [950] 4- [3- (R, S) -fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-tri Fluorophenyl) prop-2-ynyl] piperidine-4-carboxylic acid
    [951] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-tri Fluorophenyl) prop-2-ynyl] piperidine-4-carboxylic acid
    [952] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1-heptylpiperidine-4-acetic acid
    [953] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4-phenylbutyl] piperidine-4-acetic acid
    [954] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine-4-acetic acid
    [955] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (2-fluorophenyl) propyl] piperidine-4-acetic acid
    [956] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (3-fluorophenyl) propyl] piperidine-4-acetic acid
    [957] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenyl) propyl] piperidine-4-acetic acid
    [958] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (4-fluorophenyl) butyl] piperidine-4-acetic acid
    [959] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenyl) propyl] piperidine-4-acetic acid
    [960] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (2,3-difluorophenyl) propyl] piperidine-4-acetic acid
    [961] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluorophenyl) propyl] piperidine-4-acetic acid
    [962] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (2,6-difluorophenyl) propyl] piperidine-4-acetic acid
    [963] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-difluorophenyl) propyl] piperidine-4-acetic acid
    [964] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) propyl] piperidine-4-acetic acid
    [965] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) propyl] piperidine-4-acetic acid
    [966] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) propyl] piperidine-4-acetic acid
    [967] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3-phenylthiopropyl] piperidine-4-acetic acid
    [968] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenylthio) propyl] piperidine-4-acetic acid
    [969] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenylthio) propyl] piperidine-4-acetic acid
    [970] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-fluorophenylthio) ethyl] piperidine-4-acetic acid
    [971] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenylthio) propyl] piperidine-4-acetic acid
    [972] 4- [3- (3-Chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3-difluorophenylthio) -ethyl] piperidine-4-acetic acid
    [973] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenylthio) -propyl] piperidine-4-acetic acid
    [974] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,6-difluorophenylthio) -ethyl] piperidine-4-acetic acid
    [975] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylthio) -ethyl] piperidine-4- Acetic acid
    [976] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylthio) -ethyl] piperidine-4- Acetic acid
    [977] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylthio) -ethyl] piperidine-4- Acetic acid
    [978] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) ethyl] piperidine-4-acetic acid
    [979] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy) -ethyl] piperidine-4- Acetic acid
    [980] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenoxy) -ethyl] piperidine-4- Acetic acid
    [981] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenoxy) -ethyl] piperidine-4- Acetic acid
    [982] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino) -ethyl] piperidine-4-acetic acid
    [983] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylamino) -ethyl] piperidine-4- Acetic acid
    [984] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylamino) -ethyl] piperidine-4- Acetic acid
    [985] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylamino) -ethyl] piperidine-4- Acetic acid
    [986] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluorophenylthio) -propyl] piperidine-4-acetic acid
    [987] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2-chlorophenylthio) ethyl] piperidine-4-acetic acid
    [988] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chlorophenylthio) propyl] piperidine-4-acetic acid
    [989] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3-chlorophenylthio) ethyl] piperidine-4-acetic acid
    [990] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorophenylthio) propyl] piperidine-4-acetic acid
    [991] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-chlorophenylthio) ethyl] piperidine-4-acetic acid
    [992] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chlorophenylthio) propyl] piperidine-4-acetic acid
    [993] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2-methylphenylthio) ethyl] piperidine-4-acetic acid
    [994] 4- [3- (3-Chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methylphenylthio) -propyl] piperidine-4-acetic acid
    [995] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methylphenylthio) ethyl] piperidine-4-acetic acid
    [996] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylphenylthio) -propyl] piperidine-4-acetic acid
    [997] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-methylphenylthio) ethyl] piperidine-4-acetic acid
    [998] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methylphenylthio) -propyl] piperidine-4-acetic acid
    [999] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2-trifluoromethylphenylthio) -ethyl] piperidine-4-acetic acid
    [1000] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-trifluoromethylphenylthio) -propyl] piperidine-4-acetic acid
    [1001] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3-trifluoromethylphenylthio) -ethyl] piperidine-4-acetic acid
    [1002] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethylphenylthio) -propyl] piperidine-4-acetic acid
    [1003] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-trifluoromethylphenylthio) -ethyl] piperidine-4-acetic acid
    [1004] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-trifluoromethylphenylthio) -propyl] piperidine-4-acetic acid
    [1005] 4- [3- (3-Chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2-methoxyphenylthio) -ethyl] piperidine-4-acetic acid
    [1006] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxyphenylthio) -propyl] piperidine-4-acetic acid
    [1007] 4- [3- (3-Chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methoxyphenylthio) -ethyl] piperidine-4-acetic acid
    [1008] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxyphenylthio) -propyl] piperidine-4-acetic acid
    [1009] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-methoxyphenylthio) -ethyl] piperidine-4-acetic acid
    [1010] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methoxyphenylthio) -propyl] piperidine-4-acetic acid
    [1011] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [cyclopentylmethyl] piperidine-4-acetic acid
    [1012] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentyl) ethyl] piperidine-4-acetic acid
    [1013] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine-4-acetic acid
    [1014] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine-4-acetic acid
    [1015] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclopentylthio) propyl] piperidine-4-acetic acid
    [1016] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclohexylthio) propyl] piperidine-4-acetic acid
    [1017] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl] piperidine-4-acetic acid
    [1018] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (thien-2-yl) butyl] piperidine-4-acetic acid
    [1019] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) thiopropyl] piperidine-4-acetic acid
    [1020] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) propyl] piperidine-4-acetic acid
    [1021] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (thien-3-yl) butyl] piperidine-4-acetic acid
    [1022] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-3-yl) thioethyl] piperidine-4-acetic acid
    [1023] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) thiopropyl] piperidine-4-acetic acid
    [1024] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-2-yl) propyl] piperidine-4-acetic acid
    [1025] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (1,3-thiazol-2-yl) butyl] piperidine-4-acetic acid
    [1026] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-2-yl) thioethyl] piperidine-4-acetic acid
    [1027] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-2-yl) propyl] piperidine-4-acetic acid
    [1028] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrid-2-yl) butyl] piperidine-4-acetic acid
    [1029] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-2-yl) thiopropyl] piperidine-4-acetic acid
    [1030] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-3-yl) propyl] piperidine-4-acetic acid
    [1031] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrid-3-yl) butyl] piperidine-4-acetic acid
    [1032] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-3-yl) thioethyl] piperidine-4-acetic acid
    [1033] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-3-yl) thiopropyl] piperidine-4-acetic acid
    [1034] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-4-yl) propyl] piperidine-4-acetic acid
    [1035] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrid-4-yl) butyl] piperidine-4-acetic acid
    [1036] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-4-yl) thioethyl] piperidine-4-acetic acid
    [1037] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-4-yl) thiopropyl] piperidine-4-acetic acid
    [1038] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) propyl] piperidine-4-acetic acid
    [1039] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrazin-2-yl) butyl] piperidine-4-acetic acid
    [1040] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrazin-2-yl) thioethyl] piperidine-4-acetic acid
    [1041] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) thiopropyl] piperidine-4-acetic acid
    [1042] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenyl) prop-2-ynyl] piperidine-4-acetic acid
    [1043] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4-difluorophenyl) prop-2-ynyl] piperidine-4 Acetic acid
    [1044] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4-difluorophenyl) prop-2-ynyl] piperidine-4 Acetic acid
    [1045] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) prop-2-ynyl] piperidine 4-acetic acid
    [1046] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) prop-2-ynyl] piperidine 4-acetic acid
    [1047] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) prop-2-ynyl] piperidine 4-acetic acid
    [1048] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-3-fluorophenyl) prop-2-ynyl] piperidine- 4-acetic acid
    [1049] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-4-fluorophenyl) prop-2-ynyl] piperidine- 4-acetic acid
    [1050] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-4-fluorophenyl) prop-2-ynyl] piperidine- 4-acetic acid
    [1051] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-5-fluorophenyl) prop-2-ynyl] piperidine- 4-acetic acid
    [1052] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-2-fluorophenyl) prop-2-ynyl] piperidine- 4-acetic acid
    [1053] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluoro-4-methylphenyl) prop-2-ynyl] piperidine-4 Acetic acid
    [1054] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-bis (trifluoromethyl) phenyl) prop-2-ynyl] pi Ferridine-4-acetic acid
    [1055] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperidine-4-acetic acid
    [1056] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) prop-2-ynyl] piperidine-4-acetic acid
    [1057] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-2-yl) prop-2-ynyl] piperidine 4-acetic acid
    [1058] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-4-yl) prop-2-ynyl] piperidine 4-acetic acid
    [1059] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-5-yl) prop-2-ynyl] piperidine 4-acetic acid
    [1060] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-2-yl) prop-2-ynyl] piperidine-4-acetic acid
    [1061] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-3-yl) prop-2-ynyl] piperidine-4-acetic acid
    [1062] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-4-yl) prop-2-ynyl] piperidine-4-acetic acid
    [1063] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine-4-acetic acid
    [1064] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine-4-acetic acid
    [1065] 4- [3- (3-Methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) -propyl] piperidine-4-acetic acid
    [1066] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenyl-amino) ethyl] piperidine-4-acetic acid
    [1067] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenyl-amino) ethyl] piperidine-4- Acetic acid
    [1068] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) ethyl] piperidine-4-acetic acid
    [1069] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy) -ethyl] piperidine-4- Acetic acid
    [1070] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylthio) -ethyl] piperidine-4- Acetic acid
    [1071] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine-4-acetic acid
    [1072] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl] piperidine-4-acetic acid
    [1073] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] piperidine-4-acetic acid
    [1074] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) prop-2-ynyl] piperidine 4-acetic acid
    [1075] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperidine-4-acetic acid
    [1076] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine-4-acetic acid
    [1077] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine-4-acetic acid
    [1078] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) -propyl] piperidine-4- Acetic acid
    [1079] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino) -ethyl] piperidine-4-acetic acid
    [1080] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylamino) -ethyl] piperidine-4 Acetic acid
    [1081] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) ethyl] piperidine-4-acetic acid
    [1082] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy) ethyl] -piperidine-4 Acetic acid
    [1083] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylthio) -ethyl] piperidine-4 Acetic acid
    [1084] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine-4-acetic acid
    [1085] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl] piperidine-4-acetic acid
    [1086] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] piperidine-4-acetic acid
    [1087] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) prop-2-ynyl] piperi Din-4-acetic acid
    [1088] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperidine-4-acetic acid
    [1089] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine-4-acetic acid
    [1090] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine-4-acetic acid
    [1091] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) -propyl] piperidine-4- Acetic acid
    [1092] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino) -ethyl] piperidine-4-acetic acid
    [1093] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenyl-amino) ethyl] piperidine-4 Acetic acid
    [1094] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) -ethyl] piperidine-4-acetic acid
    [1095] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy) -ethyl] piperidine-4 Acetic acid
    [1096] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylthio) -ethyl] piperidine-4 Acetic acid
    [1097] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) -ethyl] piperidine-4-acetic acid
    [1098] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thio-ethyl] piperidine-4-acetic acid
    [1099] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thio-ethyl] piperidine-4-acetic acid
    [1100] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) prop-2-ynyl] piperi Din-4-acetic acid
    [1101] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperidine-4-acetic acid
    [1102] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine-4-acetic acid
    [1103] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine-4-acetic acid
    [1104] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) -propyl] piperidine-4 Acetic acid
    [1105] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenyl-amino) ethyl] piperidine-4- Acetic acid
    [1106] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenyl-amino) ethyl] piperidine- 4-acetic acid
    [1107] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) -ethyl] piperidine-4- Acetic acid
    [1108] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy) -ethyl] piperidine- 4-acetic acid
    [1109] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylthio) -ethyl] piperidine- 4-acetic acid
    [1110] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) -ethyl] piperidine-4-acetic acid
    [1111] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl] -piperidine-4-acetic acid
    [1112] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] -piperidine-4-acetic acid
    [1113] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) prop-2-ynyl] pi Ferridine-4-acetic acid
    [1114] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperidine-4- Acetic acid
    [1115] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine-4-acetic acid
    [1116] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine-4-acetic acid
    [1117] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) -propyl] piperidine-4 Acetic acid
    [1118] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino) -ethyl] piperidine-4- Acetic acid
    [1119] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylamino) -ethyl] piperidine- 4-acetic acid
    [1120] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) -ethyl] piperidine-4- Acetic acid
    [1121] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy) -ethyl] piperidine- 4-acetic acid
    [1122] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylthio) -ethyl] piperidine- 4-acetic acid
    [1123] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) -ethyl] piperidine-4-acetic acid
    [1124] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl] piperidine-4-acetic acid
    [1125] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] piperidine-4-acetic acid
    [1126] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) prop-2-ynyl] pi Ferridine-4-acetic acid
    [1127] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperidine-4- Acetic acid
    [1128] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine-4-acetic acid
    [1129] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine-4-acetic acid
    [1130] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) -propyl] piperidine-4- Acetic acid
    [1131] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino) -ethyl] piperidine-4-acetic acid
    [1132] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylamino) -ethyl] piperidine-4 Acetic acid
    [1133] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) -ethyl] piperidine-4-acetic acid
    [1134] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy) -ethyl] piperidine-4 Acetic acid
    [1135] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylthio) -ethyl] piperidine-4 Acetic acid
    [1136] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) -ethyl] piperidine-4-acetic acid
    [1137] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl] piperidine-4-acetic acid
    [1138] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] piperidine-4-acetic acid
    [1139] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) prop-2-ynyl] piperi Din-4-acetic acid
    [1140] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperidine-4-acetic acid
    [1141] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) -ethyl] piperidine-4-acetic acid
    [1142] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine-4-acetic acid
    [1143] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) -propyl] piperidine- 4-acetic acid
    [1144] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenyl-amino) ethyl] piperidine-4 Acetic acid
    [1145] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenyl-amino) ethyl] piperidine 4-acetic acid
    [1146] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) -ethyl] piperidine-4 Acetic acid
    [1147] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy) -ethyl] piperidine 4-acetic acid
    [1148] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenyl-thio) ethyl] piperidine 4-acetic acid
    [1149] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentyl-thio) ethyl] piperidine-4-acetic acid
    [1150] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl] -piperidine-4-acetic acid
    [1151] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] -piperidine-4-acetic acid
    [1152] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) -prop-2-ynyl Piperidine-4-acetic acid
    [1153] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperidine-4 Acetic acid
    [1154] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) -propyl] piperidine-4-acetic acid
    [1155] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylthio) -ethyl] piperidine-4- Acetic acid
    [1156] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylthio) -ethyl] piperidine-4- Acetic acid
    [1157] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylamino) -ethyl] piperidine-4- Acetic acid
    [1158] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylamino) -ethyl] piperidine-4- Acetic acid
    [1159] 4- [3- (3-Methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenoxy) ethyl] -piperidine-4- Acetic acid
    [1160] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenoxy) ethyl] -piperidine-4- Acetic acid
    [1161] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) prop-2-ynyl] piperidine 4-acetic acid
    [1162] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) prop-2-ynyl] piperidine 4-acetic acid
    [1163] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) propyl] -piperidine-4- Acetic acid
    [1164] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) propyl] -piperidine-4- Acetic acid
    [1165] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylthio) ethyl] -piperidine-4 Acetic acid
    [1166] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylthio) ethyl] -piperidine-4 Acetic acid
    [1167] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylamino) -ethyl] piperidine-4 Acetic acid
    [1168] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylamino) -ethyl] piperidine-4 Acetic acid
    [1169] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenoxy) ethyl] -piperidine-4 Acetic acid
    [1170] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenoxy) ethyl] -piperidine-4 Acetic acid
    [1171] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) prop-2-ynyl] piperi Din-4-acetic acid
    [1172] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) prop-2-ynyl] piperi Din-4-acetic acid
    [1173] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) -propyl] piperidine-4- Acetic acid
    [1174] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) -propyl] piperidine-4- Acetic acid
    [1175] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylthio) -ethyl] piperidine-4 Acetic acid
    [1176] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylthio) -ethyl] piperidine-4 Acetic acid
    [1177] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenyl-amino) ethyl] piperidine-4 Acetic acid
    [1178] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenyl-amino) ethyl] piperidine-4 Acetic acid
    [1179] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenoxy) -ethyl] piperidine-4 Acetic acid
    [1180] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenoxy) -ethyl] piperidine-4 Acetic acid
    [1181] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) prop-2-ynyl] piperi Din-4-acetic acid
    [1182] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) prop-2-ynyl] piperi Din-4-acetic acid
    [1183] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) -propyl] piperidine-4 Acetic acid
    [1184] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylthio) -ethyl] piperidine- 4-acetic acid
    [1185] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylthio) -ethyl] piperidine- 4-acetic acid
    [1186] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylamino) -ethyl] piperidine- 4-acetic acid
    [1187] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylamino) -ethyl] piperidine- 4-acetic acid
    [1188] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenoxy) -ethyl] piperidine- 4-acetic acid
    [1189] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenoxy) -ethyl] piperidine- 4-acetic acid
    [1190] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) prop-2-ynyl] pi Ferridine-4-acetic acid
    [1191] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) prop-2-ynyl] pi Ferridine-4-acetic acid
    [1192] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) -propyl] piperidine-4 Acetic acid
    [1193] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) -propyl] piperidine-4 Acetic acid
    [1194] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylthio) -ethyl] piperidine- 4-acetic acid
    [1195] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylthio) -ethyl] piperidine- 4-acetic acid
    [1196] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylamino) -ethyl] piperidine- 4-acetic acid
    [1197] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylamino) -ethyl] piperidine- 4-acetic acid
    [1198] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenoxy) -ethyl] piperidine- 4-acetic acid
    [1199] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenoxy) ethyl] -piperidine- 4-acetic acid
    [1200] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) prop-2-ynyl] pi Ferridine-4-acetic acid
    [1201] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) prop-2-ynyl] pi Ferridine-4-acetic acid
    [1202] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) -propyl] piperidine-4- Acetic acid
    [1203] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) -propyl] piperidine-4- Acetic acid
    [1204] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylthio) -ethyl] piperidine-4 Acetic acid
    [1205] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylthio) -ethyl] piperidine-4 Acetic acid
    [1206] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylamino) -ethyl] piperidine-4 Acetic acid
    [1207] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylamino) -ethyl] piperidine-4 Acetic acid
    [1208] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenoxy) -ethyl] piperidine-4 Acetic acid
    [1209] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenoxy) -ethyl] piperidine-4 Acetic acid
    [1210] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) prop-2-ynyl] piperi Din-4-acetic acid
    [1211] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) prop-2-ynyl] piperi Din-4-acetic acid
    [1212] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) -propyl] piperidine- 4-acetic acid
    [1213] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) -propyl] piperidine- 4-acetic acid
    [1214] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylthio) -ethyl] piperidine 4-acetic acid
    [1215] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylthio) -ethyl] piperidine 4-acetic acid
    [1216] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenyl-amino) ethyl] piperidine 4-acetic acid
    [1217] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenyl-amino) ethyl] piperidine 4-acetic acid
    [1218] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro-phenoxy) ethyl] piperidine 4-acetic acid
    [1219] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro-phenoxy) ethyl] piperidine 4-acetic acid
    [1220] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro-phenyl) prop-2-ynyl Piperidine-4-acetic acid
    [1221] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro-phenyl) prop-2-ynyl Piperidine-4-acetic acid
    [1222] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1-heptylpiperidine-4-acetic acid
    [1223] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4-phenylbutyl] -piperidine-4-acetic acid
    [1224] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] -piperidine-4 Acetic acid
    [1225] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (2-fluorophenyl) -propyl] py Ferridine-4-acetic acid
    [1226] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (3-fluorophenyl) -propyl] py Ferridine-4-acetic acid
    [1227] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenyl) -propyl] py Ferridine-4-acetic acid
    [1228] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (4-fluorophenyl) -butyl] py Ferridine-4-acetic acid
    [1229] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluoro-phenyl) Propyl] piperidine-4-acetic acid
    [1230] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (2,3-difluoro-phenyl) Propyl] piperidine-4-acetic acid
    [1231] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluoro-phenyl) Propyl] piperidine-4-acetic acid
    [1232] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (2,6-difluoro-phenyl) Propyl] piperidine-4-acetic acid
    [1233] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-difluoro-phenyl) Propyl] piperidine-4-acetic acid
    [1234] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl ) Propyl] piperidine-4-acetic acid
    [1235] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl ) Propyl] piperidine-4-acetic acid
    [1236] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl ) Propyl] piperidine-4-acetic acid
    [1237] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3-phenylthio-propyl] piperidine-4- Acetic acid
    [1238] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenylthio) propyl] py Ferridine-4-acetic acid
    [1239] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenylthio) propyl] py Ferridine-4-acetic acid
    [1240] 314- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-fluorophenylthio) ethyl] pi Ferridine-4-acetic acid
    [1241] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenylthio) propyl] py Ferridine-4-acetic acid
    [1242] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3-difluorophenylthio) Ethyl] piperidine-4-acetic acid
    [1243] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenylthio) Propyl] piperidine-4-acetic acid
    [1244] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,6-difluorophenylthio) Ethyl] piperidine-4-acetic acid
    [1245] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenyl Thio) ethyl] piperidine-4-acetic acid
    [1246] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenyl Thio) ethyl] piperidine-4-acetic acid
    [1247] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenyl Thio) ethyl] piperidine-4-acetic acid
    [1248] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) Ethyl] piperidine-4-acetic acid
    [1249] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy Ethyl] piperidine-4-acetic acid
    [1250] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenoxy Ethyl] piperidine-4-acetic acid
    [1251] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenoxy Ethyl] piperidine-4-acetic acid
    [1252] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino) Ethyl] piperidine-4-acetic acid
    [1253] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenyl Amino) ethyl] piperidine-4-acetic acid
    [1254] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenyl Amino) ethyl] piperidine-4-acetic acid
    [1255] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenyl Amino) ethyl] piperidine-4-acetic acid
    [1256] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluorophenylthio) Propyl] piperidine-4-acetic acid
    [1257] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2-chlorophenylthio) ethyl] piperi Din-4-acetic acid
    [1258] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chlorophenylthio) propyl] piperi Din-4-acetic acid
    [1259] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3-chlorophenylthio) ethyl] piperi Din-4-acetic acid
    [1260] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorophenylthio) propyl] piperi Din-4-acetic acid
    [1261] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-chlorophenylthio) ethyl] piperi Din-4-acetic acid
    [1262] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chlorophenylthio) propyl] piperi Din-4-acetic acid
    [1263] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2-methylphenylthio) ethyl] piperidine 4-acetic acid
    [1264] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methylphenylthio) propyl] piperidine 4-acetic acid
    [1265] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methylphenylthio) ethyl] piperidine 4-acetic acid
    [1266] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylphenylthio) propyl] piperidine 4-acetic acid
    [1267] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-methylphenylthio) ethyl] piperidine 4-acetic acid
    [1268] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methylphenylthio) propyl] piperidine 4-acetic acid
    [1269] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2-trifluoromethylphenylthio) ethyl] Piperidine-4-acetic acid
    [1270] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-trifluoromethylphenylthio) propyl] Piperidine-4-acetic acid
    [1271] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3-trifluoromethylphenylthio) ethyl] Piperidine-4-acetic acid
    [1272] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethylphenylthio) propyl] Piperidine-4-acetic acid
    [1273] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-trifluoromethylphenylthio) ethyl] Piperidine-4-acetic acid
    [1274] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-trifluoromethylphenylthio) propyl] Piperidine-4-acetic acid
    [1275] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2-methoxyphenylthio) ethyl] py Ferridine-4-acetic acid
    [1276] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxyphenylthio) propyl] py Ferridine-4-acetic acid
    [1277] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methoxyphenylthio) ethyl] py Ferridine-4-acetic acid
    [1278] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxyphenylthio) propyl] py Ferridine-4-acetic acid
    [1279] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-methoxyphenylthio) ethyl] py Ferridine-4-acetic acid
    [1280] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methoxyphenylthio) propyl] py Ferridine-4-acetic acid
    [1281] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [cyclopentylmethyl] piperidine-4-acetic acid
    [1282] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentyl) ethyl] piperidine-4 Acetic acid
    [1283] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine-4 Acetic acid
    [1284] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine- 4-acetic acid
    [1285] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclopentylthio) propyl] piperidine- 4-acetic acid
    [1286] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclohexylthio) propyl] piperidine- 4-acetic acid
    [1287] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl] Piperidine-4-acetic acid
    [1288] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (thien-2-yl) butyl] piperi Din-4-acetic acid
    [1289] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) thiopropyl] py Ferridine-4-acetic acid
    [1290] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) propyl] piperi Din-4-acetic acid
    [1291] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (thien-3-yl) butyl] piperi Din-4-acetic acid
    [1292] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] py Ferridine-4-acetic acid
    [1293] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-3-yl) thioethyl] py Ferridine-4-acetic acid
    [1294] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) thiopropyl] py Ferridine-4-acetic acid
    [1295] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-2-yl ) Propyl] piperidine-4-acetic acid
    [1296] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (1,3-thiazol-2-yl ) Butyl] piperidine-4-acetic acid
    [1297] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-2-yl ) Thioethyl] piperidine-4-acetic acid
    [1298] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-2-yl) propyl] py Ferridine-4-acetic acid
    [1299] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrid-2-yl) butyl] pi Ferridine-4-acetic acid
    [1300] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-2-yl) thiopropyl] Piperidine-4-acetic acid
    [1301] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-3-yl) propyl] py Ferridine-4-acetic acid
    [1302] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrid-3-yl) butyl] pi Ferridine-4-acetic acid
    [1303] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-3-yl) thioethyl] Piperidine-4-acetic acid
    [1304] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-3-yl) thiopropyl] Piperidine-4-acetic acid
    [1305] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-4-yl) propyl] py Ferridine-4-acetic acid
    [1306] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrid-4-yl) butyl] pi Ferridine-4-acetic acid
    [1307] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-4-yl) thioethyl] Piperidine-4-acetic acid
    [1308] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-4-yl) thiopropyl] Piperidine-4-acetic acid
    [1309] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) propyl] piperi Din-4-acetic acid
    [1310] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrazin-2-yl) butyl] piperi Din-4-acetic acid
    [1311] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrazin-2-yl) thioethyl] py Ferridine-4-acetic acid
    [1312] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) thiopropyl] py Ferridine-4-acetic acid
    [1313] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenyl) prop-2 -Inyl] piperidine-4-acetic acid
    [1314] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4-difluorophenyl) prop Ph-2-inyl] piperidine-4-acetic acid
    [1315] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4-difluorophenyl) prop Ph-2-inyl] piperidine-4-acetic acid
    [1316] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl ) Prop-2-ynyl] piperidine-4-acetic acid
    [1317] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl ) Prop-2-ynyl] piperidine-4-acetic acid
    [1318] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl ) Prop-2-ynyl] piperidine-4-acetic acid
    [1319] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-3-fluorophenyl) Prop-2-ynyl] piperidine-4-acetic acid
    [1320] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-4-fluorophenyl) Prop-2-ynyl] piperidine-4-acetic acid
    [1321] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-4-fluorophenyl) Prop-2-ynyl] piperidine-4-acetic acid
    [1322] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-5-fluorophenyl) Prop-2-ynyl] piperidine-4-acetic acid
    [1323] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-2-fluorophenyl) Prop-2-ynyl] piperidine-4-acetic acid
    [1324] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluoro-4-methylphenyl) prop Ph-2-inyl] piperidine-4-acetic acid
    [1325] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-bis (trifluoromethyl ) Phenyl) prop-2-ynyl] piperidine-4-acetic acid
    [1326] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2 -Inyl] piperidine-4-acetic acid
    [1327] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) prop-2 -Inyl] piperidine-4-acetic acid
    [1328] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-2-yl ) Prop-2-ynyl] piperidine-4-acetic acid
    [1329] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-4-yl ) Prop-2-ynyl] piperidine-4-acetic acid
    [1330] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-5-yl ) Prop-2-ynyl] piperidine-4-acetic acid
    [1331] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-2-yl) prop- 2-ynyl] piperidine-4-acetic acid
    [1332] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-3-yl) prop- 2-ynyl] piperidine-4-acetic acid
    [1333] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-4-yl) prop- 2-ynyl] piperidine-4-acetic acid
    [1334] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine-4 Acetic acid
    [1335] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine-4- Acetic acid
    [1336] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl ) Propyl] piperidine-4-acetic acid
    [1337] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino) Ethyl] piperidine-4-acetic acid
    [1338] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenyl Amino) ethyl] piperidine-4-acetic acid
    [1339] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) Ethyl] piperidine-4-acetic acid
    [1340] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy Ethyl] piperidine-4-acetic acid
    [1341] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenyl Thio) ethyl] piperidine-4-acetic acid
    [1342] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine- 4-acetic acid
    [1343] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl] Piperidine-4-acetic acid
    [1344] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] py Ferridine-4-acetic acid
    [1345] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl ) Prop-2-ynyl] piperidine-4-acetic acid
    [1346] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2 -Inyl] piperidine-4-acetic acid
    [1347] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine- 4-acetic acid
    [1348] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine-4 Acetic acid
    [1349] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Phenyl) propyl] piperidine-4-acetic acid
    [1350] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino ) Ethyl] piperidine-4-acetic acid
    [1351] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenylamino) ethyl] piperidine-4-acetic acid
    [1352] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy ) Ethyl] piperidine-4-acetic acid
    [1353] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenoxy) ethyl] piperidine-4-acetic acid
    [1354] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenylthio) ethyl] piperidine-4-acetic acid
    [1355] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine 4-acetic acid
    [1356] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl Piperidine-4-acetic acid
    [1357] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] Piperidine-4-acetic acid
    [1358] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Phenyl) prop-2-ynyl] piperidine-4-acetic acid
    [1359] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop- 2-ynyl] piperidine-4-acetic acid
    [1360] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine- 4-acetic acid
    [1361] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine-4 Acetic acid
    [1362] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Phenyl) propyl] piperidine-4-acetic acid
    [1363] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino ) Ethyl] piperidine-4-acetic acid
    [1364] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenylamino) ethyl] piperidine-4-acetic acid
    [1365] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy ) Ethyl] piperidine-4-acetic acid
    [1366] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenoxy) ethyl] piperidine-4-acetic acid
    [1367] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenylthio) ethyl] piperidine-4-acetic acid
    [1368] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine 4-acetic acid
    [1369] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl Piperidine-4-acetic acid
    [1370] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] Piperidine-4-acetic acid
    [1371] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Phenyl) prop-2-ynyl] piperidine-4-acetic acid
    [1372] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop- 2-ynyl] piperidine-4-acetic acid
    [1373] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine 4-acetic acid
    [1374] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine- 4-acetic acid
    [1375] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Lophenyl) propyl] piperidine-4-acetic acid
    [1376] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenyl Amino) ethyl] piperidine-4-acetic acid
    [1377] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Lophenylamino) ethyl] piperidine-4-acetic acid
    [1378] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy Ethyl] piperidine-4-acetic acid
    [1379] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Lofenoxy) ethyl] piperidine-4-acetic acid
    [1380] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Rophenylthio) ethyl] piperidine-4-acetic acid
    [1381] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperi Din-4-acetic acid
    [1382] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thio Ethyl] piperidine-4-acetic acid
    [1383] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl Piperidine-4-acetic acid
    [1384] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Lophenyl) prop-2-ynyl] piperidine-4-acetic acid
    [1385] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop -2-ynyl] piperidine-4-acetic acid
    [1386] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine 4-acetic acid
    [1387] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine- 4-acetic acid
    [1388] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Lophenyl) propyl] piperidine-4-acetic acid
    [1389] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenyl Amino) ethyl] piperidine-4-acetic acid
    [1390] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Lophenylamino) ethyl] piperidine-4-acetic acid
    [1391] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy Ethyl] piperidine-4-acetic acid
    [1392] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Lofenoxy) ethyl] piperidine-4-acetic acid
    [1393] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Rophenylthio) ethyl] piperidine-4-acetic acid
    [1394] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperi Din-4-acetic acid
    [1395] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thio Ethyl] piperidine-4-acetic acid
    [1396] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl Piperidine-4-acetic acid
    [1397] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Lophenyl) prop-2-ynyl] piperidine-4-acetic acid
    [1398] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop -2-ynyl] piperidine-4-acetic acid
    [1399] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine- 4-acetic acid
    [1400] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine-4 Acetic acid
    [1401] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Phenyl) propyl] piperidine-4-acetic acid
    [1402] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino ) Ethyl] piperidine-4-acetic acid
    [1403] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenylamino) ethyl] piperidine-4-acetic acid
    [1404] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy ) Ethyl] piperidine-4-acetic acid
    [1405] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenoxy) ethyl] piperidine-4-acetic acid
    [1406] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenylthio) ethyl] piperidine-4-acetic acid
    [1407] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine 4-acetic acid
    [1408] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl Piperidine-4-acetic acid
    [1409] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] Piperidine-4-acetic acid
    [1410] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Phenyl) prop-2-ynyl] piperidine-4-acetic acid
    [1411] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop- 2-ynyl] piperidine-4-acetic acid
    [1412] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperi Din-4-acetic acid
    [1413] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine 4-acetic acid
    [1414] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-tri Fluorophenyl) propyl] piperidine-4-acetic acid
    [1415] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluoro Phenylamino) ethyl] piperidine-4-acetic acid
    [1416] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-tri Fluorophenylamino) ethyl] piperidine-4-acetic acid
    [1417] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluoro Phenoxy) ethyl] piperidine-4-acetic acid
    [1418] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-tri Fluorophenoxy) ethyl] piperidine-4-acetic acid
    [1419] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-tri Fluorophenylthio) ethyl] piperidine-4-acetic acid
    [1420] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] py Ferridine-4-acetic acid
    [1421] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) Thioethyl] piperidine-4-acetic acid
    [1422] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thio Ethyl] piperidine-4-acetic acid
    [1423] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-tri Fluorophenyl) prop-2-ynyl] piperidine-4-acetic acid
    [1424] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) pro Ph-2-inyl] piperidine-4-acetic acid
    [1425] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl ) Propyl] piperidine-4-acetic acid
    [1426] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl ) Propyl] piperidine-4-acetic acid
    [1427] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenyl Thio) ethyl] piperidine-4-acetic acid
    [1428] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenyl Thio) ethyl] piperidine-4-acetic acid
    [1429] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenyl Amino) ethyl] piperidine-4-acetic acid
    [1430] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenyl Amino) ethyl] piperidine-4-acetic acid
    [1431] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenoxy Ethyl] piperidine-4-acetic acid
    [1432] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenoxy Ethyl] piperidine-4-acetic acid
    [1433] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl ) Prop-2-ynyl] piperidine-4-acetic acid
    [1434] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl ) Prop-2-ynyl] piperidine-4-acetic acid
    [1435] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) propyl] piperidine-4-acetic acid
    [1436] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Phenyl) propyl] piperidine-4-acetic acid
    [1437] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenylthio) ethyl] piperidine-4-acetic acid
    [1438] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenylthio) ethyl] piperidine-4-acetic acid
    [1439] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenylamino) ethyl] piperidine-4-acetic acid
    [1440] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenylamino) ethyl] piperidine-4-acetic acid
    [1441] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenoxy) ethyl] piperidine-4-acetic acid
    [1442] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenoxy) ethyl] piperidine-4-acetic acid
    [1443] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) prop-2-ynyl] piperidine-4-acetic acid
    [1444] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Phenyl) prop-2-ynyl] piperidine-4-acetic acid
    [1445] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) propyl] piperidine-4-acetic acid
    [1446] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Phenyl) propyl] piperidine-4-acetic acid
    [1447] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenylthio) ethyl] piperidine-4-acetic acid
    [1448] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenylthio) ethyl] piperidine-4-acetic acid
    [1449] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenylamino) ethyl] piperidine-4-acetic acid
    [1450] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenylamino) ethyl] piperidine-4-acetic acid
    [1451] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenoxy) ethyl] piperidine-4-acetic acid
    [1452] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenoxy) ethyl] piperidine-4-acetic acid
    [1453] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) prop-2-ynyl] piperidine-4-acetic acid
    [1454] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Phenyl) prop-2-ynyl] piperidine-4-acetic acid
    [1455] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Lophenyl) propyl] piperidine-4-acetic acid
    [1456] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Rophenylthio) ethyl] piperidine-4-acetic acid
    [1457] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Rophenylthio) ethyl] piperidine-4-acetic acid
    [1458] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Lophenylamino) ethyl] piperidine-4-acetic acid
    [1459] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Lophenylamino) ethyl] piperidine-4-acetic acid
    [1460] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Lofenoxy) ethyl] piperidine-4-acetic acid
    [1461] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Lofenoxy) ethyl] piperidine-4-acetic acid
    [1462] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Lophenyl) prop-2-ynyl] piperidine-4-acetic acid
    [1463] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Lophenyl) prop-2-ynyl] piperidine-4-acetic acid
    [1464] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Lophenyl) propyl] piperidine-4-acetic acid
    [1465] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Lophenyl) propyl] piperidine-4-acetic acid
    [1466] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Rophenylthio) ethyl] piperidine-4-acetic acid
    [1467] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Rophenylthio) ethyl] piperidine-4-acetic acid
    [1468] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Lophenylamino) ethyl] piperidine-4-acetic acid
    [1469] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Lophenylamino) ethyl] piperidine-4-acetic acid
    [1470] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Lofenoxy) ethyl] piperidine-4-acetic acid
    [1471] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Lofenoxy) ethyl] piperidine-4-acetic acid
    [1472] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Lophenyl) prop-2-ynyl] piperidine-4-acetic acid
    [1473] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Lophenyl) prop-2-ynyl] piperidine-4-acetic acid
    [1474] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) propyl] piperidine-4-acetic acid
    [1475] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Phenyl) propyl] piperidine-4-acetic acid
    [1476] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenylthio) ethyl] piperidine-4-acetic acid
    [1477] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenylthio) ethyl] piperidine-4-acetic acid
    [1478] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenylamino) ethyl] piperidine-4-acetic acid
    [1479] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenylamino) ethyl] piperidine-4-acetic acid
    [1480] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenoxy) ethyl] piperidine-4-acetic acid
    [1481] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenoxy) ethyl] piperidine-4-acetic acid
    [1482] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) prop-2-ynyl] piperidine-4-acetic acid
    [1483] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Phenyl) prop-2-ynyl] piperidine-4-acetic acid
    [1484] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-tri Fluorophenyl) propyl] piperidine-4-acetic acid
    [1485] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-tri Fluorophenyl) propyl] piperidine-4-acetic acid
    [1486] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-tri Fluorophenylthio) ethyl] piperidine-4-acetic acid
    [1487] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-tri Fluorophenylthio) ethyl] piperidine-4-acetic acid
    [1488] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-tri Fluorophenylamino) ethyl] piperidine-4-acetic acid
    [1489] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-tri Fluorophenylamino) ethyl] piperidine-4-acetic acid
    [1490] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-tri Fluorophenoxy) ethyl] piperidine-4-acetic acid
    [1491] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-tri Fluorophenoxy) ethyl] piperidine-4-acetic acid
    [1492] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-tri Fluorophenyl) prop-2-ynyl] piperidine-4-acetic acid
    [1493] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-tri Fluorophenyl) prop-2-ynyl] piperidine-4-acetic acid
    [1494] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1-heptylpiperidine-4-acetic acid
    [1495] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4-phenylbutyl] piperidine-4-acetic acid
    [1496] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine-4- Acetic acid
    [1497] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (2-fluorophenyl) propyl] piperi Din-4-acetic acid
    [1498] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (3-fluorophenyl) propyl] piperi Din-4-acetic acid
    [1499] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenyl) propyl] piperi Din-4-acetic acid
    [1500] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (4-fluorophenyl) butyl] piperi Din-4-acetic acid
    [1501] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenyl) propyl Piperidine-4-acetic acid
    [1502] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (2,3-difluorophenyl) propyl Piperidine-4-acetic acid
    [1503] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluorophenyl) propyl Piperidine-4-acetic acid
    [1504] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (2,6-difluorophenyl) propyl Piperidine-4-acetic acid
    [1505] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-difluorophenyl) propyl Piperidine-4-acetic acid
    [1506] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl ) Propyl] piperidine-4-acetic acid
    [1507] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl ) Propyl] piperidine-4-acetic acid
    [1508] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl ) Propyl] piperidine-4-acetic acid
    [1509] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3-phenylthio-propyl] piperidine-4- Acetic acid
    [1510] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenylthio) propyl] py Ferridine-4-acetic acid
    [1511] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenylthio) propyl] py Ferridine-4-acetic acid
    [1512] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-fluorophenylthio) ethyl] py Ferridine-4-acetic acid
    [1513] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenylthio) propyl] py Ferridine-4-acetic acid
    [1514] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3-difluorophenylthio) Ethyl] piperidine-4-acetic acid
    [1515] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenylthio) Propyl] piperidine-4-acetic acid
    [1516] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,6-difluorophenylthio) Ethyl] piperidine-4-acetic acid
    [1517] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenyl Thio) ethyl] piperidine-4-acetic acid
    [1518] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenyl Thio) ethyl] piperidine-4-acetic acid
    [1519] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenyl Thio) ethyl] piperidine-4-acetic acid
    [1520] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) Ethyl] piperidine-4-acetic acid
    [1521] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy Ethyl] piperidine-4-acetic acid
    [1522] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenoxy Ethyl] piperidine-4-acetic acid
    [1523] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenoxy Ethyl] piperidine-4-acetic acid
    [1524] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino) Ethyl] piperidine-4-acetic acid
    [1525] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenyl Amino) ethyl] piperidine-4-acetic acid
    [1526] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenyl Amino) ethyl] piperidine-4-acetic acid
    [1527] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenyl Amino) ethyl] piperidine-4-acetic acid
    [1528] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluorophenylthio) Propyl] piperidine-4-acetic acid
    [1529] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2-chlorophenylthio) ethyl] piperi Din-4-acetic acid
    [1530] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chlorophenylthio) propyl] piperi Din-4-acetic acid
    [1531] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3-chlorophenylthio) ethyl] piperi Din-4-acetic acid
    [1532] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorophenylthio) propyl] piperi Din-4-acetic acid
    [1533] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-chlorophenylthio) ethyl] piperi Din-4-acetic acid
    [1534] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chlorophenylthio) propyl] piperi Din-4-acetic acid
    [1535] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2-methylphenylthio) ethyl] piperidine 4-acetic acid
    [1536] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methylphenylthio) propyl] piperidine 4-acetic acid
    [1537] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methylphenylthio) ethyl] piperidine 4-acetic acid
    [1538] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylphenylthio) propyl] piperidine 4-acetic acid
    [1539] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-methylphenylthio) ethyl] piperidine 4-acetic acid
    [1540] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methylphenylthio) propyl] piperidine 4-acetic acid
    [1541] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2-trifluoromethylphenylthio) ethyl] Piperidine-4-acetic acid
    [1542] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-trifluoromethylphenylthio) propyl] Piperidine-4-acetic acid
    [1543] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3-trifluoromethylphenylthio) ethyl] Piperidine-4-acetic acid
    [1544] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethylphenylthio) propyl] Piperidine-4-acetic acid
    [1545] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-trifluoromethylphenylthio) ethyl] Piperidine-4-acetic acid
    [1546] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-trifluoromethylphenylthio) propyl] Piperidine-4-acetic acid
    [1547] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2-methoxyphenylthio) ethyl] py Ferridine-4-acetic acid
    [1548] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxyphenylthio) propyl] py Ferridine-4-acetic acid
    [1549] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methoxyphenylthio) ethyl] py Ferridine-4-acetic acid
    [1550] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxyphenylthio) propyl] py Ferridine-4-acetic acid
    [1551] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-methoxyphenylthio) ethyl] py Ferridine-4-acetic acid
    [1552] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methoxyphenylthio) propyl] py Ferridine-4-acetic acid
    [1553] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [cyclopentylmethyl] piperidine-4-acetic acid
    [1554] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentyl) ethyl] piperidine-4 Acetic acid
    [1555] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine-4 Acetic acid
    [1556] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine- 4-acetic acid
    [1557] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclopentylthio) propyl] piperidine- 4-acetic acid
    [1558] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclohexylthio) propyl] piperidine- 4-acetic acid
    [1559] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl] Piperidine-4-acetic acid
    [1560] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (thien-2-yl) butyl] piperi Din-4-acetic acid
    [1561] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) thiopropyl] py Ferridine-4-acetic acid
    [1562] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) propyl] piperi Din-4-acetic acid
    [1563] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (thien-3-yl) butyl] piperi Din-4-acetic acid
    [1564] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] py Ferridine-4-acetic acid
    [1565] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-3-yl) thioethyl] py Ferridine-4-acetic acid
    [1566] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) thiopropyl] py Ferridine-4-acetic acid
    [1567] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-2-yl ) Propyl] piperidine-4-acetic acid
    [1568] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (1,3-thiazol-2-yl ) Butyl] piperidine-4-acetic acid
    [1569] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-2-yl ) Thioethyl] piperidine-4-acetic acid
    [1570] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-2-yl) propyl] py Ferridine-4-acetic acid
    [1571] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrid-2-yl) butyl] pi Ferridine-4-acetic acid
    [1572] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-2-yl) thiopropyl] Piperidine-4-acetic acid
    [1573] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-3-yl) propyl] py Ferridine-4-acetic acid
    [1574] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrid-3-yl) butyl] pi Ferridine-4-acetic acid
    [1575] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-3-yl) thioethyl] Piperidine-4-acetic acid
    [1576] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-3-yl) thiopropyl] Piperidine-4-acetic acid
    [1577] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-4-yl) propyl] py Ferridine-4-acetic acid
    [1578] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrid-4-yl) butyl] pi Ferridine-4-acetic acid
    [1579] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-4-yl) thioethyl] Piperidine-4-acetic acid
    [1580] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-4-yl) thiopropyl] Piperidine-4-acetic acid
    [1581] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) propyl] piperi Din-4-acetic acid
    [1582] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrazin-2-yl) butyl] piperi Din-4-acetic acid
    [1583] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrazin-2-yl) thioethyl] py Ferridine-4-acetic acid
    [1584] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) thiopropyl] py Ferridine-4-acetic acid
    [1585] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenyl) prop-2 -Inyl] piperidine-4-acetic acid
    [1586] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4-difluorophenyl) prop Ph-2-inyl] piperidine-4-acetic acid
    [1587] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4-difluorophenyl) prop Ph-2-inyl] piperidine-4-acetic acid
    [1588] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl ) Prop-2-ynyl] piperidine-4-acetic acid
    [1589] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl ) Prop-2-ynyl] piperidine-4-acetic acid
    [1590] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl ) Prop-2-ynyl] piperidine-4-acetic acid
    [1591] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-3-fluorophenyl) Prop-2-ynyl] piperidine-4-acetic acid
    [1592] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-4-fluorophenyl) Prop-2-ynyl] piperidine-4-acetic acid
    [1593] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-4-fluorophenyl) Prop-2-ynyl] piperidine-4-acetic acid
    [1594] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-5-fluorophenyl) Prop-2-ynyl] piperidine-4-acetic acid
    [1595] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-2-fluorophenyl) Prop-2-ynyl] piperidine-4-acetic acid
    [1596] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluoro-4-methylphenyl) prop Ph-2-inyl] piperidine-4-acetic acid
    [1597] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-bis (trifluoromethyl ) Phenyl) prop-2-ynyl] piperidine-4-acetic acid
    [1598] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2 -Inyl] piperidine-4-acetic acid
    [1599] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) prop-2 -Inyl] piperidine-4-acetic acid
    [1600] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-2-yl ) Prop-2-ynyl] piperidine-4-acetic acid
    [1601] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-4-yl ) Prop-2-ynyl] piperidine-4-acetic acid
    [1602] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-5-yl ) Prop-2-ynyl] piperidine-4-acetic acid
    [1603] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-2-yl) prop- 2-ynyl] piperidine-4-acetic acid
    [1604] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-3-yl) prop- 2-ynyl] piperidine-4-acetic acid
    [1605] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-4-yl) prop- 2-ynyl] piperidine-4-acetic acid
    [1606] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine-4 Acetic acid
    [1607] 4- [3- (R, S) -fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine-4- Acetic acid
    [1608] 4- [3- (R, S) -fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl ) Propyl] piperidine-4-acetic acid
    [1609] 4- [3- (R, S) -fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino) Ethyl] piperidine-4-acetic acid
    [1610] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenyl Amino) ethyl] piperidine-4-acetic acid
    [1611] 4- [3- (R, S) -fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) Ethyl] piperidine-4-acetic acid
    [1612] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy Ethyl] piperidine-4-acetic acid
    [1613] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine- 4-acetic acid
    [1614] 4- [3- (R, S) -fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl] Piperidine-4-acetic acid
    [1615] 4- [3- (R, S) -fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] py Ferridine-4-acetic acid
    [1616] 4- [3- (R, S) -fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl ) Prop-2-ynyl] piperidine-4-acetic acid
    [1617] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2 -Inyl] piperidine-4-acetic acid
    [1618] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine- 4-acetic acid
    [1619] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine-4 Acetic acid
    [1620] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Phenyl) propyl] piperidine-4-acetic acid
    [1621] 4- [3- (R, S) -fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino ) Ethyl] piperidine-4-acetic acid
    [1622] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenylamino) ethyl] piperidine-4-acetic acid
    [1623] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy ) Ethyl] piperidine-4-acetic acid
    [1624] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenoxy) ethyl] piperidine-4-acetic acid
    [1625] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenylthio) ethyl] piperidine-4-acetic acid
    [1626] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine 4-acetic acid
    [1627] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl Piperidine-4-acetic acid
    [1628] 4- [3- (R, S) -fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] Piperidine-4-acetic acid
    [1629] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Phenyl) prop-2-ynyl] piperidine-4-acetic acid
    [1630] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop- 2-ynyl] piperidine-4-acetic acid
    [1631] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine- 4-acetic acid
    [1632] 4- [3- (R, S) -fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine-4 Acetic acid
    [1633] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Phenyl) propyl] piperidine-4-acetic acid
    [1634] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino ) Ethyl] piperidine-4-acetic acid
    [1635] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenylamino) ethyl] piperidine-4-acetic acid
    [1636] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy ) Ethyl] piperidine-4-acetic acid
    [1637] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenoxy) ethyl] piperidine-4-acetic acid
    [1638] 4- [3- (R, S) -fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine 4-acetic acid
    [1639] 4- [3- (R, S) -fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl Piperidine-4-acetic acid
    [1640] 4- [3- (R, S) -fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] Piperidine-4-acetic acid
    [1641] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Phenyl) prop-2-ynyl] piperidine-4-acetic acid
    [1642] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop- 2-ynyl] piperidine-4-acetic acid
    [1643] 4- [3- (R, S) -fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine 4-acetic acid
    [1644] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine- 4-acetic acid
    [1645] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Lophenyl) propyl] piperidine-4-acetic acid
    [1646] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenyl Amino) ethyl] piperidine-4-acetic acid
    [1647] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Lophenylamino) ethyl] piperidine-4-acetic acid
    [1648] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy Ethyl] piperidine-4-acetic acid
    [1649] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Lofenoxy) ethyl] piperidine-4-acetic acid
    [1650] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Rophenylthio) ethyl] piperidine-4-acetic acid
    [1651] 4- [3- (R, S) -fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperi Din-4-acetic acid
    [1652] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thio Ethyl] piperidine-4-acetic acid
    [1653] 4- [3- (R, S) -fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl Piperidine-4-acetic acid
    [1654] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Lophenyl) prop-2-ynyl] piperidine-4-acetic acid
    [1655] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop -2-ynyl] piperidine-4-acetic acid
    [1656] 4- [3- (R, S) -fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine 4-acetic acid
    [1657] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine- 4-acetic acid
    [1658] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Lophenyl) propyl] piperidine-4-acetic acid
    [1659] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenyl Amino) ethyl] piperidine-4-acetic acid
    [1660] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Lophenylamino) ethyl] piperidine-4-acetic acid
    [1661] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy Ethyl] piperidine-4-acetic acid
    [1662] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Rophenylthio) ethyl] piperidine-4-acetic acid
    [1663] 4- [3- (R, S) -fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperi Din-4-acetic acid
    [1664] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thio Ethyl] piperidine-4-acetic acid
    [1665] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl Piperidine-4-acetic acid
    [1666] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Lophenyl) prop-2-ynyl] piperidine-4-acetic acid
    [1667] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop -2-ynyl] piperidine-4-acetic acid
    [1668] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine- 4-acetic acid
    [1669] 4- [3- (R, S) -fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine-4 Acetic acid
    [1670] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Phenyl) propyl] piperidine-4-acetic acid
    [1671] 4- [3- (R, S) -fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino ) Ethyl] piperidine-4-acetic acid
    [1672] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenylamino) ethyl] piperidine-4-acetic acid
    [1673] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy ) Ethyl] piperidine-4-acetic acid
    [1674] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenoxy) ethyl] piperidine-4-acetic acid
    [1675] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenylthio) ethyl] piperidine-4-acetic acid
    [1676] 4- [3- (R, S) -fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine 4-acetic acid
    [1677] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl Piperidine-4-acetic acid
    [1678] 4- [3- (R, S) -fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] Piperidine-4-acetic acid
    [1679] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Phenyl) prop-2-ynyl] piperidine-4-acetic acid
    [1680] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop- 2-ynyl] piperidine-4-acetic acid
    [1681] 4- [3- (R, S) -fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperi Din-4-acetic acid
    [1682] 4- [3- (R, S) -fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine 4-acetic acid
    [1683] 4- [3- (R, S) -fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-tri Fluorophenyl) propyl] piperidine-4-acetic acid
    [1684] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluoro Phenylamino) ethyl] piperidine-4-acetic acid
    [1685] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-tri Fluorophenylamino) ethyl] piperidine-4-acetic acid
    [1686] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluoro Phenoxy) ethyl] piperidine-4-acetic acid
    [1687] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-tri Fluorophenoxy) ethyl] piperidine-4-acetic acid
    [1688] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-tri Fluorophenylthio) ethyl] piperidine-4-acetic acid
    [1689] 4- [3- (R, S) -fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] py Ferridine-4-acetic acid
    [1690] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) Thioethyl] piperidine-4-acetic acid
    [1691] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thio Ethyl] piperidine-4-acetic acid
    [1692] 4- [3- (R, S) -fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-tri Fluorophenyl) prop-2-ynyl] piperidine-4-acetic acid
    [1693] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop Ph-2-inyl] piperidine-4-acetic acid
    [1694] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl ) Propyl] piperidine-4-acetic acid
    [1695] 4- [3- (R, S) -fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl ) Propyl] piperidine-4-acetic acid
    [1696] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenyl Thio) ethyl] piperidine-4-acetic acid
    [1697] 4- [3- (R, S) -fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenyl Thio) ethyl] piperidine-4-acetic acid
    [1698] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenyl Amino) ethyl] piperidine-4-acetic acid
    [1699] 4- [3- (R, S) -fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenyl Amino) ethyl] piperidine-4-acetic acid
    [1700] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenoxy Ethyl] piperidine-4-acetic acid
    [1701] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenoxy Ethyl] piperidine-4-acetic acid
    [1702] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl ) Prop-2-ynyl] piperidine-4-acetic acid
    [1703] 4- [3- (R, S) -fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl ) Prop-2-ynyl] piperidine-4-acetic acid
    [1704] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) propyl] piperidine-4-acetic acid
    [1705] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Phenyl) propyl] piperidine-4-acetic acid
    [1706] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenylthio) ethyl] piperidine-4-acetic acid
    [1707] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenylthio) ethyl] piperidine-4-acetic acid
    [1708] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenylamino) ethyl] piperidine-4-acetic acid
    [1709] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenylamino) ethyl] piperidine-4-acetic acid
    [1710] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenoxy) ethyl] piperidine-4-acetic acid
    [1711] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenoxy) ethyl] piperidine-4-acetic acid
    [1712] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) prop-2-ynyl] piperidine-4-acetic acid
    [1713] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Phenyl) prop-2-ynyl] piperidine-4-acetic acid
    [1714] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) propyl] piperidine-4-acetic acid
    [1715] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Phenyl) propyl] piperidine-4-acetic acid
    [1716] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenylthio) ethyl] piperidine-4-acetic acid
    [1717] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenylthio) ethyl] piperidine-4-acetic acid
    [1718] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenylamino) ethyl] piperidine-4-acetic acid
    [1719] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenylamino) ethyl] piperidine-4-acetic acid
    [1720] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenoxy) ethyl] piperidine-4-acetic acid
    [1721] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenoxy) ethyl] piperidine-4-acetic acid
    [1722] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) prop-2-ynyl] piperidine-4-acetic acid
    [1723] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Phenyl) prop-2-ynyl] piperidine-4-acetic acid
    [1724] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) propyl] piperidine-4-acetic acid
    [1725] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Lophenyl) propyl] piperidine-4-acetic acid
    [1726] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Rophenylthio) ethyl] piperidine-4-acetic acid
    [1727] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Rophenylthio) ethyl] piperidine-4-acetic acid
    [1728] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Lophenylamino) ethyl] piperidine-4-acetic acid
    [1729] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Lophenylamino) ethyl] piperidine-4-acetic acid
    [1730] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Lofenoxy) ethyl] piperidine-4-acetic acid
    [1731] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Lofenoxy) ethyl] piperidine-4-acetic acid
    [1732] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Lophenyl) prop-2-ynyl] piperidine-4-acetic acid
    [1733] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Lophenyl) prop-2-ynyl] piperidine-4-acetic acid
    [1734] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Lophenyl) propyl] piperidine-4-acetic acid
    [1735] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Lophenyl) propyl] piperidine-4-acetic acid
    [1736] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Rophenylthio) ethyl] piperidine-4-acetic acid
    [1737] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Rophenylthio) ethyl] piperidine-4-acetic acid
    [1738] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Lophenylamino) ethyl] piperidine-4-acetic acid
    [1739] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Lophenylamino) ethyl] piperidine-4-acetic acid
    [1740] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Lofenoxy) ethyl] piperidine-4-acetic acid
    [1741] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Lofenoxy) ethyl] piperidine-4-acetic acid
    [1742] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Lophenyl) prop-2-ynyl] piperidine-4-acetic acid
    [1743] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Lophenyl) prop-2-ynyl] piperidine-4-acetic acid
    [1744] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) propyl] piperidine-4-acetic acid
    [1745] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Phenyl) propyl] piperidine-4-acetic acid
    [1746] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenylthio) ethyl] piperidine-4-acetic acid
    [1747] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenylthio) ethyl] piperidine-4-acetic acid
    [1748] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenylamino) ethyl] piperidine-4-acetic acid
    [1749] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenylamino) ethyl] piperidine-4-acetic acid
    [1750] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenoxy) ethyl] piperidine-4-acetic acid
    [1751] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenoxy) ethyl] piperidine-4-acetic acid
    [1752] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) prop-2-ynyl] piperidine-4-acetic acid
    [1753] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Phenyl) prop-2-ynyl] piperidine-4-acetic acid
    [1754] 4- [3- (R, S) -fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-tri Fluorophenyl) propyl] piperidine-4-acetic acid
    [1755] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-tri Fluorophenyl) propyl] piperidine-4-acetic acid
    [1756] 4- [3- (R, S) -fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-tri Fluorophenylthio) ethyl] piperidine-4-acetic acid
    [1757] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-tri Fluorophenylthio) ethyl] piperidine-4-acetic acid
    [1758] 4- [3- (R, S) -fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-tri Fluorophenylamino) ethyl] piperidine-4-acetic acid
    [1759] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-tri Fluorophenylamino) ethyl] piperidine-4-acetic acid
    [1760] 4- [3- (R, S) -fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-tri Fluorophenoxy) ethyl] piperidine-4-acetic acid
    [1761] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-tri Fluorophenoxy) ethyl] piperidine-4-acetic acid
    [1762] 4- [3- (R, S) -fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-tri Fluorophenyl) prop-2-ynyl] piperidine-4-acetic acid
    [1763] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-tri Fluorophenyl) prop-2-ynyl] piperidine-4-acetic acid
    [1764] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1-heptylpiperid-4-ylmethanol
    [1765] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4-phenylbutyl] piperid-4-ylmethanol
    [1766] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (2-fluorophenyl) propyl] piperid-4-ylmethanol
    [1767] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (3-fluorophenyl) propyl] piperid-4-ylmethanol
    [1768] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenyl) propyl] piperid-4-ylmethanol
    [1769] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (4-fluorophenyl) butyl] piperid-4-ylmethanol
    [1770] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenyl) propyl] piperid-4-ylmethanol
    [1771] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (2,3-difluorophenyl) propyl] piperid-4-ylmethanol
    [1772] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluorophenyl) propyl] piperid-4-ylmethanol
    [1773] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (2,6-difluorophenyl) propyl] piperid-4-ylmethanol
    [1774] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-difluorophenyl) propyl] piperid-4-ylmethanol
    [1775] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) -propyl] piperid-4-ylmethanol
    [1776] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) -propyl] piperid-4-ylmethanol
    [1777] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) -propyl] piperid-4-ylmethanol
    [1778] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3-phenylthiopropyl] piperid-4-ylmethanol
    [1779] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenylthio) propyl] piperid-4-ylmethanol
    [1780] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenylthio) propyl] piperid-4-ylmethanol
    [1781] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-fluorophenylthio) ethyl] piperid-4-ylmethanol
    [1782] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenylthio) propyl] piperid-4-ylmethanol
    [1783] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3-difluorophenyl-thio) ethyl] piperid-4-ylmethanol
    [1784] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenyl-thio) propyl] piperid-4-ylmethanol
    [1785] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,6-difluorophenyl-thio) ethyl] piperid-4-ylmethanol
    [1786] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenyl-thio) ethyl] piperid-4-yl Methanol
    [1787] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenyl-thio) ethyl] piperid-4-yl Methanol
    [1788] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenyl-thio) ethyl] piperid-4-yl Methanol
    [1789] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy) -ethyl] piperid-4-yl Methanol
    [1790] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenoxy) -ethyl] piperid-4-yl Methanol
    [1791] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenoxy) -ethyl] piperid-4-yl Methanol
    [1792] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino) -ethyl] piperid-4-ylmethanol
    [1793] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylamino) -ethyl] piperid-4-yl Methanol
    [1794] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylamino) -ethyl] piperid-4-yl Methanol
    [1795] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylamino) -ethyl] piperid-4-yl Methanol
    [1796] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluorophenylthio) -propyl] piperid-4-ylmethanol
    [1797] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2-chlorophenylthio) ethyl] piperid-4-ylmethanol
    [1798] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chlorophenylthio) propyl] piperid-4-ylmethanol
    [1799] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3-chlorophenylthio) ethyl] piperid-4-ylmethanol
    [1800] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorophenylthio) propyl] piperid-4-ylmethanol
    [1801] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-chlorophenylthio) ethyl] piperid-4-ylmethanol
    [1802] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chlorophenylthio) propyl] piperid-4-ylmethanol
    [1803] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2-methylphenylthio) ethyl] piperid-4-ylmethanol
    [1804] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methylphenylthio) propyl] piperid-4-ylmethanol
    [1805] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methylphenylthio) ethyl] piperid-4-ylmethanol
    [1806] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylphenylthio) propyl] piperid-4-ylmethanol
    [1807] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-methylphenylthio) ethyl] piperid-4-ylmethanol
    [1808] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methylphenylthio) propyl] piperid-4-ylmethanol
    [1809] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2-trifluoromethylphenylthio) -ethyl] piperid-4-ylmethanol
    [1810] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-trifluoromethylphenylthio) -propyl] piperid-4-ylmethanol
    [1811] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3-trifluoromethylphenylthio) -ethyl] piperid-4-ylmethanol
    [1812] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethylphenylthio) -propyl] piperid-4-ylmethanol
    [1813] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-trifluoromethylphenylthio) -ethyl] piperid-4-ylmethanol
    [1814] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-trifluoromethylphenylthio) -propyl] piperid-4-ylmethanol
    [1815] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2-methoxyphenylthio) ethyl] piperid-4-ylmethanol
    [1816] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxyphenylthio) -propyl] piperid-4-ylmethanol
    [1817] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methoxyphenylthio) ethyl] piperid-4-ylmethanol
    [1818] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxyphenylthio) -propyl] piperid-4-ylmethanol
    [1819] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-methoxyphenylthio) ethyl] piperid-4-ylmethanol
    [1820] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methoxyphenylthio) -propyl] piperid-4-ylmethanol
    [1821] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [cyclopentylmethyl] piperid-4-ylmethanol
    [1822] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentyl) ethyl] piperid-4-ylmethanol
    [1823] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperid-4-ylmethanol
    [1824] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclopentylthio) propyl] piperid-4-ylmethanol
    [1825] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclohexylthio) propyl] piperid-4-ylmethanol
    [1826] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (thien-2-yl) butyl] piperid-4-ylmethanol
    [1827] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) thiopropyl] piperid-4-ylmethanol
    [1828] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) propyl] piperid-4-ylmethanol
    [1829] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (thien-3-yl) butyl] piperid-4-ylmethanol
    [1830] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-3-yl) thioethyl] piperid-4-ylmethanol
    [1831] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) thiopropyl] piperid-4-ylmethanol
    [1832] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-2-yl) propyl] piperid-4-ylmethanol
    [1833] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (1,3-thiazol-2-yl) butyl] piperid-4-ylmethanol
    [1834] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-2-yl) thioethyl] piperid-4-ylmethanol
    [1835] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-2-yl) propyl] piperid-4-ylmethanol
    [1836] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrid-2-yl) butyl] piperid-4-ylmethanol
    [1837] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-2-yl) thiopropyl] piperid-4-ylmethanol
    [1838] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-3-yl) propyl] piperid-4-ylmethanol
    [1839] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrid-3-yl) butyl] piperid-4-ylmethanol
    [1840] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-3-yl) thioethyl] piperid-4-ylmethanol
    [1841] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-3-yl) thiopropyl] piperid-4-ylmethanol
    [1842] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-4-yl) propyl] piperid-4-ylmethanol
    [1843] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrid-4-yl) butyl] piperid-4-ylmethanol
    [1844] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-4-yl) thioethyl] piperid-4-ylmethanol
    [1845] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-4-yl) thiopropyl] piperid-4-ylmethanol
    [1846] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) propyl] piperid-4-ylmethanol
    [1847] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrazin-2-yl) butyl] piperid-4-ylmethanol
    [1848] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrazin-2-yl) thioethyl] piperid-4-ylmethanol
    [1849] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) thiopropyl] piperid-4-ylmethanol
    [1850] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenyl) prop-2-ynyl] piperid-4-ylmethanol
    [1851] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4-difluorophenyl) prop-2-ynyl] piperid-4- Ethanol
    [1852] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4-difluorophenyl) prop-2-ynyl] piperid-4- Ethanol
    [1853] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) prop-2-ynyl] piperid- 4-ylmethanol
    [1854] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) prop-2-ynyl] piperid- 4-ylmethanol
    [1855] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) prop-2-ynyl] piperid- 4-ylmethanol
    [1856] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-3-fluorophenyl) prop-2-ynyl] piperid-4 Monomethanol
    [1857] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-4-fluorophenyl) prop-2-ynyl] piperid-4 Monomethanol
    [1858] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-4-fluorophenyl) prop-2-ynyl] piperid-4 Monomethanol
    [1859] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-5-fluorophenyl) prop-2-ynyl] piperid-4 Monomethanol
    [1860] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-2-fluorophenyl) prop-2-ynyl] piperid-4 Monomethanol
    [1861] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluoro-4-methylphenyl) prop-2-ynyl] piperid-4- Ethanol
    [1862] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-bis (trifluoromethyl) phenyl) prop-2-ynyl] pipe Lead-4-ylmethanol
    [1863] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperid-4-ylmethanol
    [1864] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) prop-2-ynyl] piperid-4-ylmethanol
    [1865] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-2-yl) prop-2-ynyl] piperid- 4-ylmethanol
    [1866] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-4-yl) prop-2-ynyl] piperid- 4-ylmethanol
    [1867] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-5-yl) prop-2-ynyl] piperid- 4-ylmethanol
    [1868] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-2-yl) prop-2-ynyl] piperid-4-ylmethanol
    [1869] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-3-yl) prop-2-ynyl] piperid-4-ylmethanol
    [1870] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-4-yl) prop-2-ynyl] piperid-4-ylmethanol
    [1871] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperid-4-ylmethanol
    [1872] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperid-4-ylmethanol
    [1873] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) propyl] piperid-4-ylmethanol
    [1874] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino) ethyl] piperid-4-ylmethanol
    [1875] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylamino) ethyl] piperid-4-ylmethanol
    [1876] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) ethyl] piperid-4-ylmethanol
    [1877] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy) -ethyl] piperid-4-yl Methanol
    [1878] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperid-4-ylmethanol
    [1879] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl] piperid-4-ylmethanol
    [1880] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] piperid-4-ylmethanol
    [1881] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) prop-2-ynyl] piperid- 4-ylmethanol
    [1882] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperid-4-ylmethanol
    [1883] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperid-4-ylmethanol
    [1884] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperid-4-ylmethanol
    [1885] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) -propyl] piperid-4-yl Methanol
    [1886] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenyl-amino) ethyl] piperid-4-ylmethanol
    [1887] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenyl-amino) ethyl] piperid-4- Ethanol
    [1888] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) ethyl] piperid-4-ylmethanol
    [1889] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy) -ethyl] piperid-4- Ethanol
    [1890] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylthio) -ethyl] piperid-4- Ethanol
    [1891] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperid-4-ylmethanol
    [1892] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl] piperid-4-ylmethanol
    [1893] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] piperid-4-ylmethanol
    [1894] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) prop-2-ynyl] piperid -4-ylmethanol
    [1895] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperid-4-ylmethanol
    [1896] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperid-4-ylmethanol
    [1897] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperid-4-ylmethanol
    [1898] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) propyl] piperid-4-ylmethanol
    [1899] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluoro-phenylamino) ethyl] piperid-4-ylmethanol
    [1900] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro-phenylamino) ethyl] piperid-4- Ethanol
    [1901] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) -ethyl] piperid-4-ylmethanol
    [1902] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy) -ethyl] piperid-4- Ethanol
    [1903] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylthio) -ethyl] piperid-4- Ethanol
    [1904] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) -ethyl] piperid-4-ylmethanol
    [1905] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl] -piperid-4-ylmethanol
    [1906] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] -piperid-4-ylmethanol
    [1907] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) prop-2-ynyl] piperid -4-ylmethanol
    [1908] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperid-4-ylmethanol
    [1909] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperid-4-ylmethanol
    [1910] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperid-4-ylmethanol
    [1911] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) -propyl] piperid-4- Ethanol
    [1912] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino) -ethyl] piperid-4-yl Methanol
    [1913] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylamino) -ethyl] piperid-4 Monomethanol
    [1914] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) -ethyl] piperid-4-yl Methanol
    [1915] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy) -ethyl] piperid-4 Monomethanol
    [1916] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylthio) -ethyl] piperid-4 Monomethanol
    [1917] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) -ethyl] piperid-4-ylmethanol
    [1918] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thio-ethyl] piperid-4-ylmethanol
    [1919] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thio-ethyl] piperid-4-ylmethanol
    [1920] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) prop-2-ynyl] pipe Lead-4-ylmethanol
    [1921] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] -piperid-4- Ethanol
    [1922] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperid-4-ylmethanol
    [1923] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperid-4-ylmethanol
    [1924] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) propyl] piperid-4-yl Methanol
    [1925] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenyl-amino) ethyl] piperid-4-yl Methanol
    [1926] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenyl-amino) ethyl] piperid-4 Monomethanol
    [1927] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) -ethyl] piperid-4-yl Methanol
    [1928] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy) -ethyl] piperid-4 Monomethanol
    [1929] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylthio) -ethyl] piperid-4 Monomethanol
    [1930] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] -piperid-4-ylmethanol
    [1931] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl] piperid-4-ylmethanol
    [1932] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] piperid-4-ylmethanol
    [1933] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) prop-2-ynyl] pipe Lead-4-ylmethanol
    [1934] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperid-4-yl Methanol
    [1935] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperid-4-ylmethanol
    [1936] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperid-4-ylmethanol
    [1937] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) -propyl] piperid-4-yl Methanol
    [1938] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino) -ethyl] piperid-4-ylmethanol
    [1939] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylamino) -ethyl] piperid-4- Ethanol
    [1940] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) -ethyl] piperid-4-ylmethanol
    [1941] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy) -ethyl] piperid-4- Ethanol
    [1942] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylthio) -ethyl] piperid-4- Ethanol
    [1943] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) -ethyl] piperid-4-ylmethanol
    [1944] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl] piperid-4-ylmethanol
    [1945] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] piperid-4-ylmethanol
    [1946] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) prop-2-ynyl] piperid -4-ylmethanol
    [1947] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperid-4-ylmethanol
    [1948] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) -ethyl] piperid-4-ylmethanol
    [1949] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperid-4-ylmethanol
    [1950] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) -propyl] piperid-4 Monomethanol
    [1951] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino) ethyl] piperid-4-yl Methanol
    [1952] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenyl-amino) ethyl] piperid- 4-ylmethanol
    [1953] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) -ethyl] piperid-4- Ethanol
    [1954] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy) -ethyl] piperid- 4-ylmethanol
    [1955] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenyl-thio) ethyl] piperide- 4-ylmethanol
    [1956] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) -ethyl] piperid-4-ylmethanol
    [1957] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl] -piperid-4-ylmethanol
    [1958] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] -piperid-4-ylmethanol
    [1959] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro-phenyl) prop-2-ynyl ] Piperid-4-ylmethanol
    [1960] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperid-4- Ethanol
    [1961] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro-phenyl) propyl] piperid-4-ylmethanol
    [1962] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro-phenyl) propyl] piperid-4-ylmethanol
    [1963] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenyl-thio) ethyl] piperid-4-yl Methanol
    [1964] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylthio) -ethyl] piperid-4-yl Methanol
    [1965] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylamino) -ethyl] piperid-4-yl Methanol
    [1966] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylamino) -ethyl] piperid-4-yl Methanol
    [1967] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenoxy) -ethyl] piperid-4-yl Methanol
    [1968] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenoxy) -ethyl] piperid-4-yl Methanol
    [1969] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) prop-2-ynyl] piperid- 4-ylmethanol
    [1970] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) prop-2-ynyl] piperid- 4-ylmethanol
    [1971] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) -propyl] piperid-4-yl Methanol
    [1972] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) -propyl] piperid-4-yl Methanol
    [1973] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylthio) -ethyl] piperid-4- Ethanol
    [1974] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylthio) -ethyl] piperid-4- Ethanol
    [1975] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenyl-amino) ethyl] piperid-4- Ethanol
    [1976] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenyl-amino) ethyl] piperid-4- Ethanol
    [1977] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenoxy) -ethyl] piperid-4- Ethanol
    [1978] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenoxy) -ethyl] piperid-4- Ethanol
    [1979] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) prop-2-ynyl] piperid -4-ylmethanol
    [1980] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) prop-2-ynyl] piperid -4-ylmethanol
    [1981] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) -propyl] piperid-4-yl Methanol
    [1982] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) -propyl] piperid-4-yl Methanol
    [1983] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenyl-thio) ethyl] piperid-4- Ethanol
    [1984] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenyl-thio) ethyl] piperid-4- Ethanol
    [1985] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenyl-amino) ethyl] piperid-4- Ethanol
    [1986] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenyl-amino) ethyl] piperid-4- Ethanol
    [1987] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenoxy) -ethyl] piperid-4- Ethanol
    [1988] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro-phenoxy) ethyl] piperid-4- Ethanol
    [1989] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) prop-2-ynyl] piperid -4-ylmethanol
    [1990] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) prop-2-ynyl] piperid -4-ylmethanol
    [1991] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro-phenyl) propyl] piperid-4- Ethanol
    [1992] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenyl-thio) ethyl] piperid-4 Monomethanol
    [1993] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenyl-thio) ethyl] piperid-4 Monomethanol
    [1994] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenyl-amino) ethyl] piperid-4 Monomethanol
    [1995] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenyl-amino) ethyl] piperid-4 Monomethanol
    [1996] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenoxy) -ethyl] piperid-4 Monomethanol
    [1997] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenoxy) -ethyl] piperid-4 Monomethanol
    [1998] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) prop-2-ynyl] pipe Lead-4-ylmethanol
    [1999] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) prop-2-ynyl] pipe Lead-4-ylmethanol
    [2000] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) propyl] piperid-4-yl Methanol
    [2001] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) propyl] piperid-4-yl Methanol
    [2002] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenyl-thio) ethyl] piperid-4 Monomethanol
    [2003] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenyl-thio) ethyl] piperid-4 Monomethanol
    [2004] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenyl-amino) ethyl] piperid-4 Monomethanol
    [2005] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenyl-amino) ethyl] piperid-4 Monomethanol
    [2006] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenoxy) -ethyl] piperid-4 Monomethanol
    [2007] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenoxy) -ethyl] piperid-4 Monomethanol
    [2008] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) prop-2-ynyl] pipe Lead-4-ylmethanol
    [2009] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) prop-2-ynyl] pipe Lead-4-ylmethanol
    [2010] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) -propyl] piperid-4-yl Methanol
    [2011] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) -propyl] piperid-4-yl Methanol
    [2012] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylthio) -ethyl] piperid-4- Ethanol
    [2013] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylthio) -ethyl] piperid-4- Ethanol
    [2014] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenyl-amino) ethyl] piperid-4- Ethanol
    [2015] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylamino) -ethyl] piperid-4- Ethanol
    [2016] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenoxy) -ethyl] piperid-4- Ethanol
    [2017] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenoxy) -ethyl] piperid-4- Ethanol
    [2018] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) prop-2-ynyl] piperid -4-ylmethanol
    [2019] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) prop-2-ynyl] piperid -4-ylmethanol
    [2020] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) -propyl] piperid-4 Monomethanol
    [2021] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) -propyl] piperid-4 Monomethanol
    [2022] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylthio) -ethyl] piperid- 4-ylmethanol
    [2023] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylthio) -ethyl] piperid- 4-ylmethanol
    [2024] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenyl-amino) ethyl] piperid- 4-ylmethanol
    [2025] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenyl-amino) ethyl] piperid- 4-ylmethanol
    [2026] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenoxy) -ethyl] piperid- 4-ylmethanol
    [2027] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenoxy) -ethyl] piperid- 4-ylmethanol
    [2028] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) -prop-2-ynyl ] Piperid-4-ylmethanol
    [2029] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) -prop-2-ynyl ] Piperid-4-ylmethanol
    [2030] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1-heptylpiperid-4-ylmethanol
    [2031] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4-phenylbutyl] piperid-4-ylmethanol
    [2032] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] -piperid-4- Ethanol
    [2033] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (2-fluorophenyl) propyl] piperid -4-ylmethanol
    [2034] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (3-fluorophenyl) propyl] piperid -4-ylmethanol
    [2035] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenyl) -propyl] pipe Lead-4-ylmethanol
    [2036] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (4-fluorophenyl) -butyl] pipe Lead-4-ylmethanol
    [2037] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenyl)- Propyl] piperid-4-ylmethanol
    [2038] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (2,3-difluorophenyl)- Propyl] piperid-4-ylmethanol
    [2039] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluorophenyl)- Propyl] piperid-4-ylmethanol
    [2040] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (2,6-difluorophenyl)- Propyl] piperid-4-ylmethanol
    [2041] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-difluorophenyl)- Propyl] piperid-4-ylmethanol
    [2042] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl ) Propyl] piperid-4-ylmethanol
    [2043] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3-phenylthio-propyl] piperid-4-yl Methanol
    [2044] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenyl-thio) propyl] Piperid-4-ylmethanol
    [2045] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl-thio) propyl] Piperid-4-ylmethanol
    [2046] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-fluorophenyl-thio) ethyl] Piperid-4-ylmethanol
    [2047] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenyl-thio) propyl] Piperid-4-ylmethanol
    [2048] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3-difluorophenyl-thio ) Ethyl] piperid-4-ylmethanol
    [2049] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenyl-thio ) Propyl] piperid-4-ylmethanol
    [2050] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,6-difluorophenyl-thio ) Ethyl] piperid-4-ylmethanol
    [2051] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenyl Thio) ethyl] piperid-4-ylmethanol
    [2052] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenyl Thio) ethyl] piperid-4-ylmethanol
    [2053] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenyl Thio) ethyl] piperid-4-ylmethanol
    [2054] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluoro-phenoxy ) Ethyl] piperid-4-ylmethanol
    [2055] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro- Phenoxy) ethyl] piperid-4-ylmethanol
    [2056] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro- Phenoxy) ethyl] piperid-4-ylmethanol
    [2057] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro- Phenoxy) ethyl] piperid-4-ylmethanol
    [2058] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluoro-phenylamino ) Ethyl] piperid-4-ylmethanol
    [2059] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro- Phenylamino) ethyl] piperid-4-ylmethanol
    [2060] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro- Phenylamino) ethyl] piperid-4-ylmethanol
    [2061] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro- Phenylamino) ethyl] piperid-4-ylmethanol
    [2062] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluoro-phenylthio ) Propyl] piperid-4-ylmethanol
    [2063] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2-chloro-phenylthio) ethyl] pipe Lead-4-ylmethanol
    [2064] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-phenylthio) propyl] pipe Lead-4-ylmethanol
    [2065] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3-chloro-phenylthio) ethyl] pipe Lead-4-ylmethanol
    [2066] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-phenylthio) propyl] pipe Lead-4-ylmethanol
    [2067] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-chloro-phenylthio) ethyl] pipe Lead-4-ylmethanol
    [2068] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-phenylthio) propyl] pipe Lead-4-ylmethanol
    [2069] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2-methylphenyl-thio) ethyl] piperid -4-ylmethanol
    [2070] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methylphenyl-thio) propyl] piperid -4-ylmethanol
    [2071] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methylphenyl-thio) ethyl] piperid -4-ylmethanol
    [2072] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylphenyl-thio) propyl] piperid -4-ylmethanol
    [2073] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-methylphenyl-thio) ethyl] piperid -4-ylmethanol
    [2074] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methylphenyl-thio) propyl] piperid -4-ylmethanol
    [2075] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2-trifluoromethyl-phenylthio) Ethyl] piperid-4-ylmethanol
    [2076] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-trifluoromethyl-phenylthio) Propyl] piperid-4-ylmethanol
    [2077] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3-trifluoromethyl-phenylthio) Ethyl] piperid-4-ylmethanol
    [2078] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethyl-phenylthio) Propyl] piperid-4-ylmethanol
    [2079] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-trifluoromethyl-phenylthio) Ethyl] piperid-4-ylmethanol
    [2080] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-trifluoromethyl-phenylthio) Propyl] piperid-4-ylmethanol
    [2081] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2-methoxyphenyl-thio) ethyl] Piperid-4-ylmethanol
    [2082] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxyphenyl-thio) propyl] Piperid-4-ylmethanol
    [2083] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methoxyphenyl-thio) ethyl] Piperid-4-ylmethanol
    [2084] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxyphenyl-thio) propyl] Piperid-4-ylmethanol
    [2085] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-methoxyphenyl-thio) ethyl] Piperid-4-ylmethanol
    [2086] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methoxyphenyl-thio) propyl] Piperid-4-ylmethanol
    [2087] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [cyclopentylmethyl] -piperid-4-ylmethanol
    [2088] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentyl) ethyl] -piperid-4 Monomethanol
    [2089] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] -piperid-4 Monomethanol
    [2090] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperid-4 Monomethanol
    [2091] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclopentylthio) -propyl] piperid- 4-ylmethanol
    [2092] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclohexylthio) propyl] piperid-4 Monomethanol
    [2093] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl] Piperid-4-ylmethanol
    [2094] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (thien-2-yl) butyl] piperid -4-ylmethanol
    [2095] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) thiopropyl] pipe Lead-4-ylmethanol
    [2096] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) propyl] piperid -4-ylmethanol
    [2097] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (thien-3-yl) butyl] piperid -4-ylmethanol
    [2098] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] pipe Lead-4-ylmethanol
    [2099] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) thiopropyl] pipe Lead-4-ylmethanol
    [2100] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-2-yl ) Propyl] piperid-4-ylmethanol
    [2101] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (1,3-thiazol-2-yl ) Butyl] piperid-4-ylmethanol
    [2102] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-2-yl ) Thioethyl] piperid-4-ylmethanol
    [2103] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-2-yl) propyl] pipe Lead-4-ylmethanol
    [2104] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrid-2-yl) butyl] pipe Lead-4-ylmethanol
    [2105] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-2-yl) thiopropyl] Piperid-4-ylmethanol
    [2106] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-3-yl) propyl] pipe Lead-4-ylmethanol
    [2107] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrid-3-yl) butyl] pipe Lead-4-ylmethanol
    [2108] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-3-yl) thioethyl] Piperid-4-ylmethanol
    [2109] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-3-yl) thiopropyl] Piperid-4-ylmethanol
    [2110] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-4-yl) propyl] pipe Lead-4-ylmethanol
    [2111] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrid-4-yl) butyl] pipe Lead-4-ylmethanol
    [2112] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-4-yl) thioethyl] Piperid-4-ylmethanol
    [2113] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-4-yl) thiopropyl] Piperid-4-ylmethanol
    [2114] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) propyl] piperid -4-ylmethanol
    [2115] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrazin-2-yl) butyl] piperid -4-ylmethanol
    [2116] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrazin-2-yl) thioethyl] pipe Lead-4-ylmethanol
    [2117] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) thiopropyl] pipe Lead-4-ylmethanol
    [2118] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenyl) prop-2 -Inyl] piperid-4-ylmethanol
    [2119] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4-difluorophenyl) prop Ph-2-inyl] piperid-4-ylmethanol
    [2120] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4-difluorophenyl) prop Ph-2-inyl] piperid-4-ylmethanol
    [2121] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl ) Prop-2-ynyl] piperid-4-ylmethanol
    [2122] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl ) Prop-2-ynyl] piperid-4-ylmethanol
    [2123] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl ) Prop-2-ynyl] piperid-4-ylmethanol
    [2124] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-3-fluorophenyl) Prop-2-ynyl] piperid-4-ylmethanol
    [2125] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-4-fluorophenyl) Prop-2-ynyl] piperid-4-ylmethanol
    [2126] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-4-fluorophenyl) Prop-2-ynyl] piperid-4-ylmethanol
    [2127] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-5-fluorophenyl) Prop-2-ynyl] piperid-4-ylmethanol
    [2128] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-2-fluorophenyl) Prop-2-ynyl] piperid-4-ylmethanol
    [2129] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluoro-4-methylphenyl) prop Ph-2-inyl] piperid-4-ylmethanol
    [2130] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-bis (trifluoromethyl ) Phenyl) prop-2-ynyl] piperid-4-ylmethanol
    [2131] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2 -Inyl] piperid-4-ylmethanol
    [2132] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) prop-2 -Inyl] piperid-4-ylmethanol
    [2133] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-2-yl ) Prop-2-ynyl] piperid-4-ylmethanol
    [2134] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-4-yl ) Prop-2-ynyl] piperid-4-ylmethanol
    [2135] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-5-yl ) Prop-2-ynyl] piperid-4-ylmethanol
    [2136] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-2-yl) prop- 2-ynyl] piperid-4-ylmethanol
    [2137] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-3-yl) prop- 2-ynyl] piperid-4-ylmethanol
    [2138] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-4-yl) prop- 2-ynyl] piperid-4-ylmethanol
    [2139] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperid-4- Ethanol
    [2140] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperid-4-yl Methanol
    [2141] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl ) Propyl] piperid-4-ylmethanol
    [2142] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino) Ethyl] piperid-4-ylmethanol
    [2143] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenyl Amino) ethyl] piperid-4-ylmethanol
    [2144] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) Ethyl] piperid-4-ylmethanol
    [2145] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy Ethyl] piperid-4-ylmethanol
    [2146] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenyl Thio) ethyl] piperid-4-ylmethanol
    [2147] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperid-4 Monomethanol
    [2148] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl] Piperid-4-ylmethanol
    [2149] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] pipe Lead-4-ylmethanol
    [2150] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl ) Prop-2-ynyl] piperid-4-ylmethanol
    [2151] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2 -Inyl] piperid-4-ylmethanol
    [2152] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperid-4 Monomethanol
    [2153] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperid-4- Ethanol
    [2154] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Phenyl) propyl] piperid-4-ylmethanol
    [2155] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino ) Ethyl] piperid-4-ylmethanol
    [2156] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenylamino) ethyl] piperid-4-ylmethanol
    [2157] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy ) Ethyl] piperid-4-ylmethanol
    [2158] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenoxy) ethyl] piperid-4-ylmethanol
    [2159] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenylthio) ethyl] piperid-4-ylmethanol
    [2160] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperid- 4-ylmethanol
    [2161] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl ] Piperid-4-ylmethanol
    [2162] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] Piperid-4-ylmethanol
    [2163] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Phenyl) prop-2-ynyl] piperid-4-ylmethanol
    [2164] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop- 2-ynyl] piperid-4-ylmethanol
    [2165] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperid-4 Monomethanol
    [2166] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperid-4- Ethanol
    [2167] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Phenyl) propyl] piperid-4-ylmethanol
    [2168] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino ) Ethyl] piperid-4-ylmethanol
    [2169] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenylamino) ethyl] piperid-4-ylmethanol
    [2170] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy ) Ethyl] piperid-4-ylmethanol
    [2171] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenoxy) ethyl] piperid-4-ylmethanol
    [2172] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenylthio) ethyl] piperid-4-ylmethanol
    [2173] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperid- 4-ylmethanol
    [2174] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl ] Piperid-4-ylmethanol
    [2175] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] Piperid-4-ylmethanol
    [2176] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Phenyl) prop-2-ynyl] piperid-4-ylmethanol
    [2177] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop- 2-ynyl] piperid-4-ylmethanol
    [2178] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperid- 4-ylmethanol
    [2179] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperid-4 Monomethanol
    [2180] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Rophenyl) propyl] piperid-4-ylmethanol
    [2181] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenyl Amino) ethyl] piperid-4-ylmethanol
    [2182] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Lophenylamino) ethyl] piperid-4-ylmethanol
    [2183] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy Ethyl] piperid-4-ylmethanol
    [2184] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Lofenoxy) ethyl] piperid-4-ylmethanol
    [2185] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Rophenylthio) ethyl] piperid-4-ylmethanol
    [2186] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperid -4-ylmethanol
    [2187] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thio Ethyl] piperid-4-ylmethanol
    [2188] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl ] Piperid-4-ylmethanol
    [2189] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Rophenyl) prop-2-ynyl] piperid-4-ylmethanol
    [2190] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop -2-ynyl] piperid-4-ylmethanol
    [2191] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperid- 4-ylmethanol
    [2192] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperid-4 Monomethanol
    [2193] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Rophenyl) propyl] piperid-4-ylmethanol
    [2194] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenyl Amino) ethyl] piperid-4-ylmethanol
    [2195] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Lophenylamino) ethyl] piperid-4-ylmethanol
    [2196] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy Ethyl] piperid-4-ylmethanol
    [2197] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Lofenoxy) ethyl] piperid-4-ylmethanol
    [2198] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Rophenylthio) ethyl] piperid-4-ylmethanol
    [2199] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperid -4-ylmethanol
    [2200] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thio Ethyl] piperid-4-ylmethanol
    [2201] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl ] Piperid-4-ylmethanol
    [2202] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Rophenyl) prop-2-ynyl] piperid-4-ylmethanol
    [2203] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop -2-ynyl] piperid-4-ylmethanol
    [2204] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperid-4 Monomethanol
    [2205] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperid-4- Ethanol
    [2206] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Phenyl) propyl] piperid-4-ylmethanol
    [2207] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino ) Ethyl] piperid-4-ylmethanol
    [2208] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenylamino) ethyl] piperid-4-ylmethanol
    [2209] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy ) Ethyl] piperid-4-ylmethanol
    [2210] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenoxy) ethyl] piperid-4-ylmethanol
    [2211] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenylthio) ethyl] piperid-4-ylmethanol
    [2212] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperid- 4-ylmethanol
    [2213] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl ] Piperid-4-ylmethanol
    [2214] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] Piperid-4-ylmethanol
    [2215] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Phenyl) prop-2-ynyl] piperid-4-ylmethanol
    [2216] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop- 2-ynyl] piperid-4-ylmethanol
    [2217] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperid -4-ylmethanol
    [2218] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperid- 4-ylmethanol
    [2219] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-tri Fluorophenyl) propyl] piperid-4-ylmethanol
    [2220] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluoro Phenylamino) ethyl] piperid-4-ylmethanol
    [2221] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-tri Fluorophenylamino) ethyl] piperid-4-ylmethanol
    [2222] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluoro Phenoxy) ethyl] piperid-4-ylmethanol
    [2223] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-tri Fluorophenoxy) ethyl] piperid-4-ylmethanol
    [2224] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-tri Fluorophenylthio) ethyl] piperid-4-ylmethanol
    [2225] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] pipe Lead-4-ylmethanol
    [2226] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) Thioethyl] piperid-4-ylmethanol
    [2227] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thio Ethyl] piperid-4-ylmethanol
    [2228] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-tri Fluorophenyl) prop-2-ynyl] piperid-4-ylmethanol
    [2229] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) pro Ph-2-inyl] piperid-4-ylmethanol
    [2230] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl ) Propyl] piperid-4-ylmethanol
    [2231] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl ) Propyl] piperid-4-ylmethanol
    [2232] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenyl Thio) ethyl] piperid-4-ylmethanol
    [2233] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenyl Thio) ethyl] piperid-4-ylmethanol
    [2234] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenyl Amino) ethyl] piperid-4-ylmethanol
    [2235] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenyl Amino) ethyl] piperid-4-ylmethanol
    [2236] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenoxy Ethyl] piperid-4-ylmethanol
    [2237] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenoxy Ethyl] piperid-4-ylmethanol
    [2238] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl ) Prop-2-ynyl] piperid-4-ylmethanol
    [2239] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl ) Prop-2-ynyl] piperid-4-ylmethanol
    [2240] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) propyl] piperid-4-ylmethanol
    [2241] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Phenyl) propyl] piperid-4-ylmethanol
    [2242] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenylthio) ethyl] piperid-4-ylmethanol
    [2243] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenylthio) ethyl] piperid-4-ylmethanol
    [2244] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenylamino) ethyl] piperid-4-ylmethanol
    [2245] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenylamino) ethyl] piperid-4-ylmethanol
    [2246] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenoxy) ethyl] piperid-4-ylmethanol
    [2247] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenoxy) ethyl] piperid-4-ylmethanol
    [2248] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) prop-2-ynyl] piperid-4-ylmethanol
    [2249] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Phenyl) prop-2-ynyl] piperid-4-ylmethanol
    [2250] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) propyl] piperid-4-ylmethanol
    [2251] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Phenyl) propyl] piperid-4-ylmethanol
    [2252] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenylthio) ethyl] piperid-4-ylmethanol
    [2253] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenylthio) ethyl] piperid-4-ylmethanol
    [2254] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenylamino) ethyl] piperid-4-ylmethanol
    [2255] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenylamino) ethyl] piperid-4-ylmethanol
    [2256] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenoxy) ethyl] piperid-4-ylmethanol
    [2257] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenoxy) ethyl] piperid-4-ylmethanol
    [2258] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) prop-2-ynyl] piperid-4-ylmethanol
    [2259] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Phenyl) prop-2-ynyl] piperid-4-ylmethanol
    [2260] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Rophenyl) propyl] piperid-4-ylmethanol
    [2261] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Rophenylthio) ethyl] piperid-4-ylmethanol
    [2262] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Rophenylthio) ethyl] piperid-4-ylmethanol
    [2263] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Lophenylamino) ethyl] piperid-4-ylmethanol
    [2264] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Lophenylamino) ethyl] piperid-4-ylmethanol
    [2265] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Lofenoxy) ethyl] piperid-4-ylmethanol
    [2266] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Lofenoxy) ethyl] piperid-4-ylmethanol
    [2267] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Rophenyl) prop-2-ynyl] piperid-4-ylmethanol
    [2268] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Rophenyl) prop-2-ynyl] piperid-4-ylmethanol
    [2269] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Rophenyl) propyl] piperid-4-ylmethanol
    [2270] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Rophenyl) propyl] piperid-4-ylmethanol
    [2271] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Rophenylthio) ethyl] piperid-4-ylmethanol
    [2272] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Rophenylthio) ethyl] piperid-4-ylmethanol
    [2273] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Lophenylamino) ethyl] piperid-4-ylmethanol
    [2274] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Lophenylamino) ethyl] piperid-4-ylmethanol
    [2275] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Lofenoxy) ethyl] piperid-4-ylmethanol
    [2276] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Lofenoxy) ethyl] piperid-4-ylmethanol
    [2277] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Rophenyl) prop-2-ynyl] piperid-4-ylmethanol
    [2278] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Rophenyl) prop-2-ynyl] piperid-4-ylmethanol
    [2279] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) propyl] piperid-4-ylmethanol
    [2280] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Phenyl) propyl] piperid-4-ylmethanol
    [2281] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenylthio) ethyl] piperid-4-ylmethanol
    [2282] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenylthio) ethyl] piperid-4-ylmethanol
    [2283] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenylamino) ethyl] piperid-4-ylmethanol
    [2284] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenylamino) ethyl] piperid-4-ylmethanol
    [2285] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenoxy) ethyl] piperid-4-ylmethanol
    [2286] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenoxy) ethyl] piperid-4-ylmethanol
    [2287] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) prop-2-ynyl] piperid-4-ylmethanol
    [2288] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Phenyl) prop-2-ynyl] piperid-4-ylmethanol
    [2289] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-tri Fluorophenyl) propyl] piperid-4-ylmethanol
    [2290] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-tri Fluorophenyl) propyl] piperid-4-ylmethanol
    [2291] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-tri Fluorophenylthio) ethyl] piperid-4-ylmethanol
    [2292] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-tri Fluorophenylthio) ethyl] piperid-4-ylmethanol
    [2293] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-tri Fluorophenylamino) ethyl] piperid-4-ylmethanol
    [2294] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-tri Fluorophenylamino) ethyl] piperid-4-ylmethanol
    [2295] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-tri Fluorophenoxy) ethyl] piperid-4-ylmethanol
    [2296] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-tri Fluorophenoxy) ethyl] piperid-4-ylmethanol
    [2297] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-tri Fluorophenyl) prop-2-ynyl] piperid-4-ylmethanol
    [2298] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-tri Fluorophenyl) prop-2-ynyl] piperid-4-ylmethanol
    [2299] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1-heptylpiperid-4-ylmethanol
    [2300] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4-phenylbutyl] piperid-4-ylmethanol
    [2301] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperid-4-yl Methanol
    [2302] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (2-fluorophenyl) propyl] piperid -4-ylmethanol
    [2303] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (3-fluorophenyl) propyl] piperid -4-ylmethanol
    [2304] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenyl) propyl] piperid -4-ylmethanol
    [2305] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (4-fluorophenyl) butyl] piperid -4-ylmethanol
    [2306] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenyl) propyl ] Piperid-4-ylmethanol
    [2307] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (2,3-difluorophenyl) propyl ] Piperid-4-ylmethanol
    [2308] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluorophenyl) propyl ] Piperid-4-ylmethanol
    [2309] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (2,6-difluorophenyl) propyl ] Piperid-4-ylmethanol
    [2310] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-difluorophenyl) propyl ] Piperid-4-ylmethanol
    [2311] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl ) Propyl] piperid-4-ylmethanol
    [2312] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl ) Propyl] piperid-4-ylmethanol
    [2313] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl ) Propyl] piperid-4-ylmethanol
    [2314] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3-phenylthio-propyl] piperid-4-yl Methanol
    [2315] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenylthio) propyl] pipe Lead-4-ylmethanol
    [2316] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenylthio) propyl] pipe Lead-4-ylmethanol
    [2317] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-fluorophenylthio) ethyl] pipe Lead-4-ylmethanol
    [2318] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenylthio) propyl] pipe Lead-4-ylmethanol
    [2319] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3-difluorophenylthio) Ethyl] piperid-4-ylmethanol
    [2320] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenylthio) Propyl] piperid-4-ylmethanol
    [2321] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,6-difluorophenylthio) Ethyl] piperid-4-ylmethanol
    [2322] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenyl Thio) ethyl] piperid-4-ylmethanol
    [2323] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenyl Thio) ethyl] piperid-4-ylmethanol
    [2324] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenyl Thio) ethyl] piperid-4-ylmethanol
    [2325] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) Ethyl] piperid-4-ylmethanol
    [2326] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy Ethyl] piperid-4-ylmethanol
    [2327] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenoxy Ethyl] piperid-4-ylmethanol
    [2328] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenoxy Ethyl] piperid-4-ylmethanol
    [2329] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino) Ethyl] piperid-4-ylmethanol
    [2330] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenyl Amino) ethyl] piperid-4-ylmethanol
    [2331] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenyl Amino) ethyl] piperid-4-ylmethanol
    [2332] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenyl Amino) ethyl] piperid-4-ylmethanol
    [2333] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluorophenylthio) Propyl] piperid-4-ylmethanol
    [2334] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2-chlorophenylthio) ethyl] piperid -4-ylmethanol
    [2335] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chlorophenylthio) propyl] piperid -4-ylmethanol
    [2336] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3-chlorophenylthio) ethyl] piperid -4-ylmethanol
    [2337] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorophenylthio) propyl] piperid -4-ylmethanol
    [2338] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-chlorophenylthio) ethyl] piperid -4-ylmethanol
    [2339] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chlorophenylthio) propyl] piperid -4-ylmethanol
    [2340] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2-methylphenylthio) ethyl] piperid- 4-ylmethanol
    [2341] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methylphenylthio) propyl] piperid- 4-ylmethanol
    [2342] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methylphenylthio) ethyl] piperid- 4-ylmethanol
    [2343] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylphenylthio) propyl] piperid- 4-ylmethanol
    [2344] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-methylphenylthio) ethyl] piperid- 4-ylmethanol
    [2345] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methylphenylthio) propyl] piperid- 4-ylmethanol
    [2346] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2-trifluoromethylphenylthio) ethyl] Piperid-4-ylmethanol
    [2347] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-trifluoromethylphenylthio) propyl] Piperid-4-ylmethanol
    [2348] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3-trifluoromethylphenylthio) ethyl] Piperid-4-ylmethanol
    [2349] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethylphenylthio) propyl] Piperid-4-ylmethanol
    [2350] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-trifluoromethylphenylthio) ethyl] Piperid-4-ylmethanol
    [2351] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-trifluoromethylphenylthio) propyl] Piperid-4-ylmethanol
    [2352] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2-methoxyphenylthio) ethyl] pipe Lead-4-ylmethanol
    [2353] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxyphenylthio) propyl] pipe Lead-4-ylmethanol
    [2354] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methoxyphenylthio) ethyl] pipe Lead-4-ylmethanol
    [2355] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxyphenylthio) propyl] pipe Lead-4-ylmethanol
    [2356] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-methoxyphenylthio) ethyl] pipe Lead-4-ylmethanol
    [2357] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methoxyphenylthio) propyl] pipe Lead-4-ylmethanol
    [2358] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [cyclopentylmethyl] piperid-4-ylmethanol
    [2359] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentyl) ethyl] piperid-4- Ethanol
    [2360] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) -ethyl] piperid-4 Monomethanol
    [2361] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) -ethyl] piperid- 4-ylmethanol
    [2362] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclopentylthio) -propyl] piperid- 4-ylmethanol
    [2363] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclohexylthio) -propyl] piperid- 4-ylmethanol
    [2364] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl] -Piperid-4-ylmethanol
    [2365] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (thien-2-yl) butyl] -pipe Lead-4-ylmethanol
    [2366] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) thiopropyl]- Piperid-4-ylmethanol
    [2367] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) propyl] -pipe Lead-4-ylmethanol
    [2368] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (thien-3-yl) butyl] -pipe Lead-4-ylmethanol
    [2369] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl]- Piperid-4-ylmethanol
    [2370] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-3-yl) thioethyl]- Piperid-4-ylmethanol
    [2371] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) thiopropyl]- Piperid-4-ylmethanol
    [2372] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-2-yl ) Propyl] piperid-4-ylmethanol
    [2373] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (1,3-thiazol-2-yl ) Butyl] piperid-4-ylmethanol
    [2374] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-2-yl ) Thioethyl] piperid-4-ylmethanol
    [2375] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-2-yl) propyl] pipe Lead-4-ylmethanol
    [2376] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrid-2-yl) butyl] pipe Lead-4-ylmethanol
    [2377] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-2-yl) thiopropyl] Piperid-4-ylmethanol
    [2378] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-3-yl) propyl] pipe Lead-4-ylmethanol
    [2379] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrid-3-yl) butyl] pipe Lead-4-ylmethanol
    [2380] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-3-yl) thioethyl] Piperid-4-ylmethanol
    [2381] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-3-yl) thiopropyl] Piperid-4-ylmethanol
    [2382] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-4-yl) propyl] pipe Lead-4-ylmethanol
    [2383] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrid-4-yl) butyl] pipe Lead-4-ylmethanol
    [2384] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-4-yl) thioethyl] Piperid-4-ylmethanol
    [2385] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-4-yl) thiopropyl] Piperid-4-ylmethanol
    [2386] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) propyl] piperid -4-ylmethanol
    [2387] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrazin-2-yl) butyl] piperid -4-ylmethanol
    [2388] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrazin-2-yl) thioethyl] pipe Lead-4-ylmethanol
    [2389] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) thiopropyl] pipe Lead-4-ylmethanol
    [2390] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenyl) prop-2 -Inyl] piperid-4-ylmethanol
    [2391] 4- [3- (R, S) -fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4-difluorophenyl) prop Ph-2-inyl] piperid-4-ylmethanol
    [2392] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4-difluorophenyl) prop Ph-2-inyl] piperid-4-ylmethanol
    [2393] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl ) Prop-2-ynyl] piperid-4-ylmethanol
    [2394] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl ) Prop-2-ynyl] piperid-4-ylmethanol
    [2395] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl ) Prop-2-ynyl] piperid-4-ylmethanol
    [2396] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-3-fluorophenyl) Prop-2-ynyl] piperid-4-ylmethanol
    [2397] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-4-fluorophenyl) Prop-2-ynyl] piperid-4-ylmethanol
    [2398] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-4-fluorophenyl) Prop-2-ynyl] piperid-4-ylmethanol
    [2399] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-5-fluorophenyl) Prop-2-ynyl] piperid-4-ylmethanol
    [2400] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-2-fluorophenyl) Prop-2-ynyl] piperid-4-ylmethanol
    [2401] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluoro-4-methylphenyl) prop Ph-2-inyl] piperid-4-ylmethanol
    [2402] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-bis (trifluoromethyl ) Phenyl) prop-2-ynyl] piperid-4-ylmethanol
    [2403] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2 -Inyl] piperid-4-ylmethanol
    [2404] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) prop-2 -Inyl] piperid-4-ylmethanol
    [2405] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-2-yl ) Prop-2-ynyl] piperid-4-ylmethanol
    [2406] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-4-yl ) Prop-2-ynyl] piperid-4-ylmethanol
    [2407] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-5-yl ) Prop-2-ynyl] piperid-4-ylmethanol
    [2408] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-2-yl) prop- 2-ynyl] piperid-4-ylmethanol
    [2409] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-3-yl) prop- 2-ynyl] piperid-4-ylmethanol
    [2410] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-4-yl) prop- 2-ynyl] piperid-4-ylmethanol
    [2411] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperid-4- Ethanol
    [2412] 4- [3- (R, S) -fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperid-4-yl Methanol
    [2413] 4- [3- (R, S) -fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl ) Propyl] piperid-4-ylmethanol
    [2414] 4- [3- (R, S) -fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino) Ethyl] piperid-4-ylmethanol
    [2415] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenyl Amino) ethyl] piperid-4-ylmethanol
    [2416] 4- [3- (R, S) -fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) Ethyl] piperid-4-ylmethanol
    [2417] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy Ethyl] piperid-4-ylmethanol
    [2418] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenyl Thio) ethyl] piperid-4-ylmethanol
    [2419] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperid-4 Monomethanol
    [2420] 4- [3- (R, S) -fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl] Piperid-4-ylmethanol
    [2421] 4- [3- (R, S) -fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] pipe Lead-4-ylmethanol
    [2422] 4- [3- (R, S) -fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl ) Prop-2-ynyl] piperid-4-ylmethanol
    [2423] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2 -Inyl] piperid-4-ylmethanol
    [2424] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperid-4 Monomethanol
    [2425] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperid-4- Ethanol
    [2426] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Phenyl) propyl] piperid-4-ylmethanol
    [2427] 4- [3- (R, S) -fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino ) Ethyl] piperid-4-ylmethanol
    [2428] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenylamino) ethyl] piperid-4-ylmethanol
    [2429] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy ) Ethyl] piperid-4-ylmethanol
    [2430] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenoxy) ethyl] piperid-4-ylmethanol
    [2431] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenylthio) ethyl] piperid-4-ylmethanol
    [2432] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperid- 4-ylmethanol
    [2433] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl ] Piperid-4-ylmethanol
    [2434] 4- [3- (R, S) -fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] Piperid-4-ylmethanol
    [2435] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Phenyl) prop-2-ynyl] piperid-4-ylmethanol
    [2436] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop- 2-ynyl] piperid-4-ylmethanol
    [2437] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperid-4 Monomethanol
    [2438] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperid-4- Ethanol
    [2439] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Phenyl) propyl] piperid-4-ylmethanol
    [2440] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino ) Ethyl] piperid-4-ylmethanol
    [2441] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenylamino) ethyl] piperid-4-ylmethanol
    [2442] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy ) Ethyl] piperid-4-ylmethanol
    [2443] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenoxy) ethyl] piperid-4-ylmethanol
    [2444] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenylthio) ethyl] piperid-4-ylmethanol
    [2445] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperid- 4-ylmethanol
    [2446] 4- [3- (R, S) -fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl ] Piperid-4-ylmethanol
    [2447] 4- [3- (R, S) -fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] Piperid-4-ylmethanol
    [2448] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Phenyl) prop-2-ynyl] piperid-4-ylmethanol
    [2449] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop- 2-ynyl] piperid-4-ylmethanol
    [2450] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperid- 4-ylmethanol
    [2451] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperid-4 Monomethanol
    [2452] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Rophenyl) propyl] piperid-4-ylmethanol
    [2453] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenyl Amino) ethyl] piperid-4-ylmethanol
    [2454] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Lophenylamino) ethyl] piperid-4-ylmethanol
    [2455] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy Ethyl] piperid-4-ylmethanol
    [2456] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Lofenoxy) ethyl] piperid-4-ylmethanol
    [2457] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Rophenylthio) ethyl] piperid-4-ylmethanol
    [2458] 4- [3- (R, S) -fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperid -4-ylmethanol
    [2459] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thio Ethyl] piperid-4-ylmethanol
    [2460] 4- [3- (R, S) -fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl ] Piperid-4-ylmethanol
    [2461] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Rophenyl) prop-2-ynyl] piperid-4-ylmethanol
    [2462] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop -2-ynyl] piperid-4-ylmethanol
    [2463] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperid- 4-ylmethanol
    [2464] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperid-4 Monomethanol
    [2465] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Rophenyl) propyl] piperid-4-ylmethanol
    [2466] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenyl Amino) ethyl] piperid-4-ylmethanol
    [2467] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Lophenylamino) ethyl] piperid-4-ylmethanol
    [2468] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy Ethyl] piperid-4-ylmethanol
    [2469] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Lofenoxy) ethyl] piperid-4-ylmethanol
    [2470] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Rophenylthio) ethyl] piperid-4-ylmethanol
    [2471] 4- [3- (R, S) -fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperid -4-ylmethanol
    [2472] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thio Ethyl] piperid-4-ylmethanol
    [2473] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl ] Piperid-4-ylmethanol
    [2474] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Rophenyl) prop-2-ynyl] piperid-4-ylmethanol
    [2475] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop -2-ynyl] piperid-4-ylmethanol
    [2476] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperid-4 Monomethanol
    [2477] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperid-4- Ethanol
    [2478] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Phenyl) propyl] piperid-4-ylmethanol
    [2479] 4- [3- (R, S) -fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino ) Ethyl] piperid-4-ylmethanol
    [2480] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenylamino) ethyl] piperid-4-ylmethanol
    [2481] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy ) Ethyl] piperid-4-ylmethanol
    [2482] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenoxy) ethyl] piperid-4-ylmethanol
    [2483] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenylthio) ethyl] piperid-4-ylmethanol
    [2484] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperid- 4-ylmethanol
    [2485] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl ] Piperid-4-ylmethanol
    [2486] 4- [3- (R, S) -fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] Piperid-4-ylmethanol
    [2487] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Phenyl) prop-2-ynyl] piperid-4-ylmethanol
    [2488] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop- 2-ynyl] piperid-4-ylmethanol
    [2489] 4- [3- (R, S) -fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperid -4-ylmethanol
    [2490] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperid- 4-ylmethanol
    [2491] 4- [3- (R, S) -fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-tri Fluorophenyl) propyl] piperid-4-ylmethanol
    [2492] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluoro Phenylamino) ethyl] piperid-4-ylmethanol
    [2493] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-tri Fluorophenylamino) ethyl] piperid-4-ylmethanol
    [2494] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluoro Phenoxy) ethyl] piperid-4-ylmethanol
    [2495] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-tri Fluorophenoxy) ethyl] piperid-4-ylmethanol
    [2496] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-tri Fluorophenylthio) ethyl] piperid-4-ylmethanol
    [2497] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] pipe Lead-4-ylmethanol
    [2498] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) Thioethyl] piperid-4-ylmethanol
    [2499] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thio Ethyl] piperid-4-ylmethanol
    [2500] 4- [3- (R, S) -fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-tri Fluorophenyl) prop-2-ynyl] piperid-4-ylmethanol
    [2501] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop Ph-2-inyl] piperid-4-ylmethanol
    [2502] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl ) Propyl] piperid-4-ylmethanol
    [2503] 4- [3- (R, S) -fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl ) Propyl] piperid-4-ylmethanol
    [2504] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenyl Thio) ethyl] piperid-4-ylmethanol
    [2505] 4- [3- (R, S) -fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenyl Thio) ethyl] piperid-4-ylmethanol
    [2506] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenyl Amino) ethyl] piperid-4-ylmethanol
    [2507] 4- [3- (R, S) -fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenyl Amino) ethyl] piperid-4-ylmethanol
    [2508] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenoxy Ethyl] piperid-4-ylmethanol
    [2509] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenoxy Ethyl] piperid-4-ylmethanol
    [2510] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl ) Prop-2-ynyl] piperid-4-ylmethanol
    [2511] 4- [3- (R, S) -fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl ) Prop-2-ynyl] piperid-4-ylmethanol
    [2512] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) propyl] piperid-4-ylmethanol
    [2513] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Phenyl) propyl] piperid-4-ylmethanol
    [2514] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenylthio) ethyl] piperid-4-ylmethanol
    [2515] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenylthio) ethyl] piperid-4-ylmethanol
    [2516] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenylamino) ethyl] piperid-4-ylmethanol
    [2517] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenylamino) ethyl] piperid-4-ylmethanol
    [2518] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenoxy) ethyl] piperid-4-ylmethanol
    [2519] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenoxy) ethyl] piperid-4-ylmethanol
    [2520] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) prop-2-ynyl] piperid-4-ylmethanol
    [2521] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Phenyl) prop-2-ynyl] piperid-4-ylmethanol
    [2522] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) propyl] piperid-4-ylmethanol
    [2523] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Phenyl) propyl] piperid-4-ylmethanol
    [2524] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenylthio) ethyl] piperid-4-ylmethanol
    [2525] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenylthio) ethyl] piperid-4-ylmethanol
    [2526] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenylamino) ethyl] piperid-4-ylmethanol
    [2527] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenylamino) ethyl] piperid-4-ylmethanol
    [2528] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenoxy) ethyl] piperid-4-ylmethanol
    [2529] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenoxy) ethyl] piperid-4-ylmethanol
    [2530] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) prop-2-ynyl] piperid-4-ylmethanol
    [2531] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Phenyl) prop-2-ynyl] piperid-4-ylmethanol
    [2532] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) propyl] piperid-4-ylmethanol
    [2533] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Rophenyl) propyl] piperid-4-ylmethanol
    [2534] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Rophenylthio) ethyl] piperid-4-ylmethanol
    [2535] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Rophenylthio) ethyl] piperid-4-ylmethanol
    [2536] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Lophenylamino) ethyl] piperid-4-ylmethanol
    [2537] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Lophenylamino) ethyl] piperid-4-ylmethanol
    [2538] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Lofenoxy) ethyl] piperid-4-ylmethanol
    [2539] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Lofenoxy) ethyl] piperid-4-ylmethanol
    [2540] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Rophenyl) prop-2-ynyl] piperid-4-ylmethanol
    [2541] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Rophenyl) prop-2-ynyl] piperid-4-ylmethanol
    [2542] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Rophenyl) propyl] piperid-4-ylmethanol
    [2543] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Rophenyl) propyl] piperid-4-ylmethanol
    [2544] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Rophenylthio) ethyl] piperid-4-ylmethanol
    [2545] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Rophenylthio) ethyl] piperid-4-ylmethanol
    [2546] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Lophenylamino) ethyl] piperid-4-ylmethanol
    [2547] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Lophenylamino) ethyl] piperid-4-ylmethanol
    [2548] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Lofenoxy) ethyl] piperid-4-ylmethanol
    [2549] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Lofenoxy) ethyl] piperid-4-ylmethanol
    [2550] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Rophenyl) prop-2-ynyl] piperid-4-ylmethanol
    [2551] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Rophenyl) prop-2-ynyl] piperid-4-ylmethanol
    [2552] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) propyl] piperid-4-ylmethanol
    [2553] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Phenyl) propyl] piperid-4-ylmethanol
    [2554] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenylthio) ethyl] piperid-4-ylmethanol
    [2555] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenylthio) ethyl] piperid-4-ylmethanol
    [2556] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenylamino) ethyl] piperid-4-ylmethanol
    [2557] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenylamino) ethyl] piperid-4-ylmethanol
    [2558] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenoxy) ethyl] piperid-4-ylmethanol
    [2559] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenoxy) ethyl] piperid-4-ylmethanol
    [2560] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) prop-2-ynyl] piperid-4-ylmethanol
    [2561] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Phenyl) prop-2-ynyl] piperid-4-ylmethanol
    [2562] 4- [3- (R, S) -fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-tri Fluorophenyl) propyl] piperid-4-ylmethanol
    [2563] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-tri Fluorophenyl) propyl] piperid-4-ylmethanol
    [2564] 4- [3- (R, S) -fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-tri Fluorophenylthio) ethyl] piperid-4-ylmethanol
    [2565] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-tri Fluorophenylthio) ethyl] piperid-4-ylmethanol
    [2566] 4- [3- (R, S) -fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-tri Fluorophenylamino) ethyl] piperid-4-ylmethanol
    [2567] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-tri Fluorophenylamino) ethyl] piperid-4-ylmethanol
    [2568] 4- [3- (R, S) -fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-tri Fluorophenoxy) ethyl] piperid-4-ylmethanol
    [2569] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-tri Fluorophenoxy) ethyl] piperid-4-ylmethanol
    [2570] 4- [3- (R, S) -fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-tri Fluorophenyl) prop-2-ynyl] piperid-4-ylmethanol
    [2571] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-tri Fluorophenyl) prop-2-ynyl] piperid-4-ylmethanol
    [2572] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1-heptyl piperidine-4-hydroxysamic acid
    [2573] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4-phenylbutyl] piperidine-4-hydroxysamic acid
    [2574] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (2-fluorophenyl) propyl] piperidine-4-hydroxysamic acid
    [2575] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (3-fluorophenyl) propyl] piperidine-4-hydroxysamic acid
    [2576] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenyl) propyl] piperidine-4-hydroxysamic acid
    [2577] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (4-fluorophenyl) butyl] piperidine-4-hydroxysamic acid
    [2578] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenyl) propyl] piperidine-4-hydroxysamic acid
    [2579] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (2,3-difluorophenyl) propyl] piperidine-4-hydroxysamic acid
    [2580] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluorophenyl) propyl] piperidine-4-hydroxysamic acid
    [2581] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (2,6-difluorophenyl) propyl] piperidine-4-hydroxysamic acid
    [2582] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-difluorophenyl) propyl] piperidine-4-hydroxysamic acid
    [2583] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) propyl] piperidine-4-hydroxy Samsan
    [2584] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) propyl] piperidine-4-hydroxy Samsan
    [2585] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) propyl] piperidine-4-hydroxy Samsan
    [2586] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3-phenylthiopropyl] piperidine-4-hydroxysamic acid
    [2587] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenylthio) propyl] piperidine-4-hydroxysamic acid
    [2588] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenylthio) propyl] piperidine-4-hydroxysamic acid
    [2589] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-fluorophenylthio) ethyl] piperidine-4-hydroxysamic acid
    [2590] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenylthio) propyl] piperidine-4-hydroxysamic acid
    [2591] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3-difluorophenylthio) ethyl] piperidine-4-hydroxysamic acid
    [2592] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenylthio) propyl] piperidine-4-hydroxysamic acid
    [2593] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,6-difluorophenylthio) ethyl] piperidine-4-hydroxysamic acid
    [2594] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylthio) ethyl] piperidine-4-hydro Roksamsan
    [2595] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylthio) ethyl] piperidine-4-hydro Roksamsan
    [2596] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylthio) ethyl] piperidine-4-hydro Roksamsan
    [2597] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy) ethyl] piperidine-4-hydro Roksamsan
    [2598] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenoxy) ethyl] piperidine-4-hydro Roksamsan
    [2599] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenoxy) ethyl] piperidine-4-hydro Roksamsan
    [2600] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino) ethyl] piperidine-4-hydroxysamic acid
    [2601] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylamino) ethyl] piperidine-4-hydro Roksamsan
    [2602] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylamino) ethyl] piperidine-4-hydro Roksamsan
    [2603] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylamino) ethyl] piperidine-4-hydro Roksamsan
    [2604] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluorophenylthio) propyl] piperidine-4-hydroxysamic acid
    [2605] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2-chlorophenylthio) ethyl] piperidine-4-hydroxysamic acid
    [2606] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chlorophenylthio) propyl] piperidine-4-hydroxysamic acid
    [2607] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3-chlorophenylthio) ethyl] piperidine-4-hydroxysamic acid
    [2608] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chlorophenylthio) propyl] piperidine-4-hydroxysamic acid
    [2609] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-chlorophenylthio) ethyl] piperidine-4-hydroxysamic acid
    [2610] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chlorophenylthio) propyl] piperidine-4-hydroxysamic acid
    [2611] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2-methylphenylthio) ethyl] piperidine-4-hydroxysamic acid
    [2612] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methylphenylthio) propyl] piperidine-4-hydroxysamic acid
    [2613] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methylphenylthio) ethyl] piperidine-4-hydroxysamic acid
    [2614] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methylphenylthio) propyl] piperidine-4-hydroxysamic acid
    [2615] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-methylphenylthio) ethyl] piperidine-4-hydroxysamic acid
    [2616] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methylphenylthio) propyl] piperidine-4-hydroxysamic acid
    [2617] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2-trifluoromethylphenylthio) ethyl] piperidine-4-hydroxysamic acid
    [2618] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-trifluoromethylphenylthio) propyl] piperidine-4-hydroxysamic acid
    [2619] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3-trifluoromethylphenylthio) ethyl] piperidine-4-hydroxysamic acid
    [2620] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-trifluoromethylphenylthio) propyl] piperidine-4-hydroxysamic acid
    [2621] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-trifluoromethylphenylthio) ethyl] piperidine-4-hydroxysamic acid
    [2622] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-trifluoromethylphenylthio) propyl] piperidine-4-hydroxysamic acid
    [2623] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2-methoxyphenylthio) ethyl] piperidine-4-hydroxysamic acid
    [2624] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-methoxyphenylthio) propyl] piperidine-4-hydroxysamic acid
    [2625] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3-methoxyphenylthio) ethyl] piperidine-4-hydroxysamic acid
    [2626] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-methoxyphenylthio) propyl] piperidine-4-hydroxysamic acid
    [2627] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4-methoxyphenylthio) ethyl] piperidine-4-hydroxysamic acid
    [2628] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-methoxyphenylthio) propyl] piperidine-4-hydroxysamic acid
    [2629] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [cyclopentylmethyl] piperidine-4-hydroxysamic acid
    [2630] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentyl) ethyl] piperidine-4-hydroxysamic acid
    [2631] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine-4-hydroxysamic acid
    [2632] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclopentylthio) propyl] piperidine-4-hydroxysamic acid
    [2633] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (cyclohexylthio) propyl] piperidine-4-hydroxysamic acid
    [2634] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (thien-2-yl) butyl] piperidine-4-hydroxysamic acid
    [2635] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) thiopropyl] piperidine-4-hydroxysamic acid
    [2636] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) propyl] piperidine-4-hydroxysamic acid
    [2637] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (thien-3-yl) butyl] piperidine-4-hydroxysamic acid
    [2638] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-3-yl) thioethyl] piperidine-4-hydroxysamic acid
    [2639] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) thiopropyl] piperidine-4-hydroxysamic acid
    [2640] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-2-yl) propyl] piperidine-4-hydroxy Samsan
    [2641] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (1,3-thiazol-2-yl) butyl] piperidine-4-hydroxy Samsan
    [2642] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-2-yl) thioethyl] piperidine-4-hydro Roksamsan
    [2643] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-2-yl) propyl] piperidine-4-hydroxysamic acid
    [2644] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrid-2-yl) butyl] piperidine-4-hydroxysamic acid
    [2645] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-2-yl) thiopropyl] piperidine-4-hydroxysamic acid
    [2646] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-3-yl) propyl] piperidine-4-hydroxysamic acid
    [2647] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrid-3-yl) butyl] piperidine-4-hydroxysamic acid
    [2648] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-3-yl) thioethyl] piperidine-4-hydroxysamic acid
    [2649] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-3-yl) thiopropyl] piperidine-4-hydroxysamic acid
    [2650] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-4-yl) propyl] piperidine-4-hydroxysamic acid
    [2651] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrid-4-yl) butyl] piperidine-4-hydroxysamic acid
    [2652] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-4-yl) thioethyl] piperidine-4-hydroxysamic acid
    [2653] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-4-yl) thiopropyl] piperidine-4-hydroxysamic acid
    [2654] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) propyl] piperidine-4-hydroxysamic acid
    [2655] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [4- (pyrazin-2-yl) butyl] piperidine-4-hydroxysamic acid
    [2656] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrazin-2-yl) thioethyl] piperidine-4-hydroxysamic acid
    [2657] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrazin-2-yl) thiopropyl] piperidine-4-hydroxysamic acid
    [2658] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenyl) prop-2-ynyl] piperidine-4-hydroxy Samsan
    [2659] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4-difluorophenyl) prop-2-ynyl] piperidine-4 Hydroxamic acid
    [2660] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4-difluorophenyl) prop-2-ynyl] piperidine-4 Hydroxamic acid
    [2661] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) prop-2-ynyl] piperidine 4-hydroxysamic acid
    [2662] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) prop-2-ynyl] piperidine 4-hydroxysamic acid
    [2663] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) prop-2-ynyl] piperidine 4-hydroxysamic acid
    [2664] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-3-fluorophenyl) prop-2-ynyl] piperidine- 4-hydroxysamic acid
    [2665] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-4-fluorophenyl) prop-2-ynyl] piperidine- 4-hydroxysamic acid
    [2666] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-chloro-4-fluorophenyl) prop-2-ynyl] piperidine- 4-hydroxysamic acid
    [2667] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-chloro-5-fluorophenyl) prop-2-ynyl] piperidine- 4-hydroxysamic acid
    [2668] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-chloro-2-fluorophenyl) prop-2-ynyl] piperidine- 4-hydroxysamic acid
    [2669] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluoro-4-methylphenyl) prop-2-ynyl] piperidine-4 Hydroxamic acid
    [2670] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-bistrifluoromethylphenyl) prop-2-ynyl] piperidine- 4-hydroxysamic acid
    [2671] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperidine-4-hydroxy Samsan
    [2672] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-3-yl) -2-ynyl] piperidine-4-hydroxysamic acid
    [2673] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-2-yl) prop-2-ynyl] piperidine 4-hydroxysamic acid
    [2674] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-4-yl) prop-2-ynyl] piperidine 4-hydroxysamic acid
    [2675] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (1,3-thiazol-5-yl) prop-2-ynyl] piperidine 4-hydroxysamic acid
    [2676] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-2-yl) prop-2-ynyl] piperidine-4-hydro Roksamsan
    [2677] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-3-yl) prop-2-ynyl] piperidine-4-hydro Roksamsan
    [2678] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3- (pyrid-4-yl) prop-2-ynyl] piperidine-4-hydro Roksamsan
    [2679] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine-4-hydroxysamic acid
    [2680] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine-4-hydroxysamic acid
    [2681] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) propyl] piperidine-4-hydroxy Samsan
    [2682] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino) ethyl] piperidine-4-hydroxysamic acid
    [2683] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylamino) ethyl] piperidine-4-hydro Roksamsan
    [2684] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) ethyl] piperidine-4-hydroxysamic acid
    [2685] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy) ethyl] piperidine-4-hydro Roksamsan
    [2686] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine-4-hydroxysamic acid
    [2687] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl] piperidine-4-hydroxysamic acid
    [2688] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] piperidine-4-hydroxysamic acid
    [2689] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) prop-2-ynyl] piperidine 4-hydroxysamic acid
    [2690] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperidine-4-hydroxy Samsan
    [2691] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine-4-hydroxysamic acid
    [2692] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine-4-hydroxysamic acid
    [2693] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) propyl] piperidine-4-hydride Roksamsan
    [2694] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino) ethyl] piperidine-4-hydroxy Samsan
    [2695] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylamino) ethyl] piperidine-4- Hydroxamic acid
    [2696] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) ethyl] piperidine-4-hydroxy Samsan
    [2697] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy) ethyl] piperidine-4- Hydroxamic acid
    [2698] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylthio) ethyl] piperidine-4- Hydroxamic acid
    [2699] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine-4-hydroxysamic acid
    [2700] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl] piperidine-4-hydroxysamic acid
    [2701] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] piperidine-4-hydroxysamic acid
    [2702] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) prop-2-ynyl] piperi Din-4-hydroxysamic acid
    [2703] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperidine-4-hydro Roksamsan
    [2704] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine-4-hydroxysamic acid
    [2705] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine-4-hydroxysamic acid
    [2706] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) propyl] piperidine-4-hydride Roksamsan
    [2707] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino) ethyl] piperidine-4-hydroxy Samsan
    [2708] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylamino) ethyl] piperidine-4- Hydroxamic acid
    [2709] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) ethyl] piperidine-4-hydroxy Samsan
    [2710] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy) ethyl] piperidine-4- Hydroxamic acid
    [2711] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylthio) ethyl] piperidine-4- Hydroxamic acid
    [2712] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine-4-hydroxysamic acid
    [2713] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl] piperidine-4-hydroxysamic acid
    [2714] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] piperidine-4-hydroxysamic acid
    [2715] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) prop-2-ynyl] piperi Din-4-hydroxysamic acid
    [2716] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperidine-4-hydro Roksamsan
    [2717] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine-4-hydroxysamic acid
    [2718] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine-4-hydroxysamic acid
    [2719] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) propyl] piperidine-4- Hydroxamic acid
    [2720] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino) ethyl] piperidine-4-hydroxy Roksamsan
    [2721] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylamino) ethyl] piperidine-4 Hydroxamic acid
    [2722] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) ethyl] piperidine-4-hydroxy Roksamsan
    [2723] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy) ethyl] piperidine-4 Hydroxamic acid
    [2724] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylthio) ethyl] piperidine-4 Hydroxamic acid
    [2725] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine-4-hydroxysamic acid
    [2726] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl] piperidine-4-hydroxysamic acid
    [2727] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] piperidine-4-hydroxysamic acid
    [2728] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) prop-2-ynyl] pi Ferridine-4-hydroxysamic acid
    [2729] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperidine-4- Hydroxamic acid
    [2730] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine-4-hydroxysamic acid
    [2731] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine-4-hydroxysamic acid
    [2732] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) propyl] piperidine-4- Hydroxamic acid
    [2733] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino) ethyl] piperidine-4-hydro Roksamsan
    [2734] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylamino) ethyl] piperidine-4 Hydroxamic acid
    [2735] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) ethyl] piperidine-4-hydro Roksamsan
    [2736] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy) ethyl] piperidine-4 Hydroxamic acid
    [2737] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylthio) ethyl] piperidine-4 Hydroxamic acid
    [2738] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine-4-hydroxysamic acid
    [2739] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl] piperidine-4-hydroxysamic acid
    [2740] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] piperidine-4-hydroxysamic acid
    [2741] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) prop-2-ynyl] pi Ferridine-4-hydroxysamic acid
    [2742] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperidine-4- Hydroxamic acid
    [2743] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine-4-hydroxysamic acid
    [2744] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine-4-hydroxysamic acid
    [2745] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) propyl] piperidine-4-hydride Roksamsan
    [2746] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino) ethyl] piperidine-4-hydroxy Samsan
    [2747] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylamino) ethyl] piperidine-4- Hydroxamic acid
    [2748] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) ethyl] piperidine-4-hydroxy Samsan
    [2749] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy) ethyl] piperidine-4- Hydroxamic acid
    [2750] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylthio) ethyl] piperidine-4- Hydroxamic acid
    [2751] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine-4-hydroxysamic acid
    [2752] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl] piperidine-4-hydroxysamic acid
    [2753] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] piperidine-4-hydroxysamic acid
    [2754] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) prop-2-ynyl] piperi Din-4-hydroxysamic acid
    [2755] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperidine-4-hydro Roksamsan
    [2756] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine-4-hydroxysamic acid
    [2757] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine-4-hydroxysamic acid
    [2758] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) propyl] piperidine-4 Hydroxamic acid
    [2759] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino) ethyl] piperidine-4- Hydroxamic acid
    [2760] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylamino) ethyl] piperidine- 4-hydroxysamic acid
    [2761] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) ethyl] piperidine-4- Hydroxamic acid
    [2762] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy) ethyl] piperidine- 4-hydroxysamic acid
    [2763] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenylthio) ethyl] piperidine- 4-hydroxysamic acid
    [2764] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthiol) ethyl] piperidine-4-hydroxysamic acid
    [2765] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl] piperidine-4-hydroxy Samsan
    [2766] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] piperidine-4-hydroxysamic acid
    [2767] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) prop-2-ynyl] Piperidine-4-hydroxysamic acid
    [2768] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop-2-ynyl] piperidine-4 Hydroxamic acid
    [2769] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) propyl] piperidine-4-hydroxy Samsan
    [2770] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) propyl] piperidine-4-hydroxy Samsan
    [2771] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylthio) ethyl] piperidine-4-hydro Roksamsan
    [2772] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylthio) ethyl] piperidine-4-hydro Roksamsan
    [2773] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylamino) ethyl] piperidine-4-hydro Roksamsan
    [2774] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylamino) ethyl] piperidine-4-hydro Roksamsan
    [2775] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenoxy) ethyl] piperidine-4-hydro Roksamsan
    [2776] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenoxy) ethyl] piperidine-4-hydro Roksamsan
    [2777] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) prop-2-ynyl] piperidine 4-hydroxysamic acid
    [2778] 4- [3- (3-methyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) prop-2-ynyl] piperidine 4-hydroxysamic acid
    [2779] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) propyl] piperidine-4-hydro Roksamsan
    [2780] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) propyl] piperidine-4-hydro Roksamsan
    [2781] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylthio) ethyl] piperidine-4- Hydroxamic acid
    [2782] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylthio) ethyl] piperidine-4- Hydroxamic acid
    [2783] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylamino) ethyl] piperidine-4- Hydroxamic acid
    [2784] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylamino) ethyl] piperidine-4- Hydroxamic acid
    [2785] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenoxy) ethyl] piperidine-4- Hydroxamic acid
    [2786] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenoxy) ethyl] piperidine-4- Hydroxamic acid
    [2787] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) prop-2-ynyl] piperi Din-4-hydroxysamic acid
    [2788] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) prop-2-ynyl] piperi Din-4-hydroxysamic acid
    [2789] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) propyl] piperidine-4-hydride Roksamsan
    [2790] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) propyl] piperidine-4-hydride Roksamsan
    [2791] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylthio) ethyl] piperidine-4- Hydroxamic acid
    [2792] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylthio) ethyl] piperidine-4- Hydroxamic acid
    [2793] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylamino) ethyl] piperidine-4- Hydroxamic acid
    [2794] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylamino) ethyl] piperidine-4- Hydroxamic acid
    [2795] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenoxy) ethyl] piperidine-4- Hydroxamic acid
    [2796] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenoxy) ethyl] piperidine-4- Hydroxamic acid
    [2797] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) prop-2-ynyl] piperi Din-4-hydroxysamic acid
    [2798] 4- [3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) prop-2-ynyl] piperi Din-4-hydroxysamic acid
    [2799] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) propyl] piperidine-4- Hydroxamic acid
    [2800] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylthio) ethyl] piperidine-4 Hydroxamic acid
    [2801] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylthio) ethyl] piperidine-4 Hydroxamic acid
    [2802] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylamino) ethyl] piperidine-4 Hydroxamic acid
    [2803] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylamino) ethyl] piperidine-4 Hydroxamic acid
    [2804] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenoxy) ethyl] piperidine-4 Hydroxamic acid
    [2805] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenoxy) ethyl] piperidine-4 Hydroxamic acid
    [2806] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) prop-2-ynyl] pi Ferridine-4-hydroxysamic acid
    [2807] 4- [3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) prop-2-ynyl] pi Ferridine-4-hydroxysamic acid
    [2808] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) propyl] piperidine-4- Hydroxamic acid
    [2809] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) propyl] piperidine-4- Hydroxamic acid
    [2810] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylthio) ethyl] piperidine-4 Hydroxamic acid
    [2811] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylthio) ethyl] piperidine-4 Hydroxamic acid
    [2812] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylamino) ethyl] piperidine-4 Hydroxamic acid
    [2813] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylamino) ethyl] piperidine-4 Hydroxamic acid
    [2814] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenoxy) ethyl] piperidine-4 Hydroxamic acid
    [2815] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenoxy) ethyl] piperidine-4 Hydroxamic acid
    [2816] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) prop-2-ynyl] pi Ferridine-4-hydroxysamic acid
    [2817] 4- [3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) prop-2-ynyl] pi Ferridine-4-hydroxysamic acid
    [2818] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) propyl] piperidine-4-hydride Roksamsan
    [2819] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) propyl] piperidine-4-hydride Roksamsan
    [2820] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylthio) ethyl] piperidine-4- Hydroxamic acid
    [2821] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylthio) ethyl] piperidine-4- Hydroxamic acid
    [2822] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylamino) ethyl] piperidine-4- Hydroxamic acid
    [2823] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylamino) ethyl] piperidine-4- Hydroxamic acid
    [2824] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenoxy) ethyl] piperidine-4- Hydroxamic acid
    [2825] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenoxy) ethyl] piperidine-4- Hydroxamic acid
    [2826] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) prop-2-ynyl] piperi Din-4-hydroxysamic acid
    [2827] 4- [3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) prop-2-ynyl] piperi Din-4-hydroxysamic acid
    [2828] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) propyl] piperidine-4 Hydroxamic acid
    [2829] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) propyl] piperidine-4 Hydroxamic acid
    [2830] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylthio) ethyl] piperidine- 4-hydroxysamic acid
    [2831] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylthio) ethyl] piperidine- 4-hydroxysamic acid
    [2832] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenylamino) ethyl] piperidine- 4-hydroxysamic acid
    [2833] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenylamino) ethyl] piperidine- 4-hydroxysamic acid
    [2834] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluorophenoxy) ethyl] piperidine- 4-hydroxysamic acid
    [2835] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenoxy) ethyl] piperidine- 4-hydroxysamic acid
    [2836] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) prop-2-ynyl] Piperidine-4-hydroxysamic acid
    [2837] 4- [3- (3-morpholinomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) prop-2-ynyl] Piperidine-4-hydroxysamic acid
    [2838] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1-heptyl piperidine-4-hydroxysamic acid
    [2839] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [4-phenylbutyl] piperidine-4-hydro Roksamsan
    [2840] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (phenyl) propyl] piperidine-4 Hydroxamic acid
    [2841] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [4- (2-fluorophenyl) propyl] py Ferridine-4-hydroxysamic acid
    [2842] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [4- (3-fluorophenyl) propyl] py Ferridine-4-hydroxysamic acid
    [2843] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-fluorophenyl) propyl] py Ferridine-4-hydroxysamic acid
    [2844] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [4- (4-fluorophenyl) butyl] py Ferridine-4-hydroxysamic acid
    [2845] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,3-difluorophenyl) Propyl] piperidine-4-hydroxysamic acid
    [2846] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [4- (2,3-difluorophenyl) Propyl] piperidine-4-hydroxysamic acid
    [2847] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,6-difluorophenyl) Propyl] piperidine-4-hydroxysamic acid
    [2848] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [4- (2,6-difluorophenyl) Propyl] piperidine-4-hydroxysamic acid
    [2849] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (3,5-difluorophenyl) Propyl] piperidine-4-hydroxysamic acid
    [2850] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,3,5-trifluoro Phenyl) propyl] piperidine-4-hydroxysamic acid
    [2851] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3-phenylthiopropyl] piperidine-4- Hydroxamic acid
    [2852] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (2-fluorophenylthio) propyl] Piperidine-4-hydroxysamic acid
    [2853] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-fluorophenylthio) propyl] Piperidine-4-hydroxysamic acid
    [2854] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (4-fluorophenylthio) ethyl] Piperidine-4-hydroxysamic acid
    [2855] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-fluorophenylthio) propyl] Piperidine-4-hydroxysamic acid
    [2856] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2,3-difluorophenylthio Ethyl] piperidine-4-hydroxysamic acid
    [2857] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,3-difluorophenylthio ) Propyl] piperidine-4-hydroxysamic acid
    [2858] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2,6-difluorophenylthio Ethyl] piperidine-4-hydroxysamic acid
    [2859] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2,3,5-trifluoro Phenylthio) ethyl] piperidine-4-hydroxysamic acid
    [2860] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2,4,6-trifluoro Phenylthio) ethyl] piperidine-4-hydroxysamic acid
    [2861] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (3,4,5-trifluoro Phenylthio) ethyl] piperidine-4-hydroxysamic acid
    [2862] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (3,5-difluorophenoxy Ethyl] piperidine-4-hydroxysamic acid
    [2863] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2,3,5-trifluoro Phenoxy) ethyl] piperidine-4-hydroxysamic acid
    [2864] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2,4,6-trifluoro Phenoxy) ethyl] piperidine-4-hydroxysamic acid
    [2865] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (3,4,5-trifluoro Phenoxy) ethyl] piperidine-4-hydroxysamic acid
    [2866] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (3,5-difluorophenylamino Ethyl] piperidine-4-hydroxysamic acid
    [2867] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2,3,5-trifluoro Phenylamino) ethyl] -piperidine-4-hydroxysamic acid
    [2868] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2,4,6-trifluoro Phenylamino) ethyl] -piperidine-4-hydroxysamic acid
    [2869] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (3,4,5-trifluoro Phenylamino) ethyl] -piperidine-4-hydroxysamic acid
    [2870] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,6-difluorophenylthio ) Propyl] piperidine-4-hydroxysamic acid
    [2871] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2-chlorophenylthio) ethyl] pi Ferridine-4-hydroxysamic acid
    [2872] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (2-chlorophenylthio) propyl] py Ferridine-4-hydroxysamic acid
    [2873] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (3-chlorophenylthio) ethyl] pi Ferridine-4-hydroxysamic acid
    [2874] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-chlorophenylthio) propyl] py Ferridine-4-hydroxysamic acid
    [2875] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (4-chlorophenylthio) ethyl] pi Ferridine-4-hydroxysamic acid
    [2876] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-chlorophenylthio) propyl] py Ferridine-4-hydroxysamic acid
    [2877] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2-methylphenylthio) ethyl] piperi Din-4-hydroxysamic acid
    [2878] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (2-methylphenylthio) propyl] piperi Din-4-hydroxysamic acid
    [2879] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (3-methylphenylthio) ethyl] piperi Din-4-hydroxysamic acid
    [2880] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-methylphenylthio) propyl] piperi Din-4-hydroxysamic acid
    [2881] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (4-methylphenylthio) ethyl] piperi Din-4-hydroxysamic acid
    [2882] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-methylphenylthio) propyl] piperi Din-4-hydroxysamic acid
    [2883] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2-trifluoromethylphenylthio) ethyl ] -Piperidine-4-hydroxysamic acid
    [2884] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (2-trifluoromethylphenylthio) propyl ] -Piperidine-4-hydroxysamic acid
    [2885] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (3-trifluoromethylphenylthio) ethyl ] -Piperidine-4-hydroxysamic acid
    [2886] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-trifluoromethylphenylthio) propyl ] -Piperidine-4-hydroxysamic acid
    [2887] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (4-trifluoromethylphenylthio) ethyl ] -Piperidine-4-hydroxysamic acid
    [2888] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-trifluoromethylphenylthio) propyl ] -Piperidine-4-hydroxysamic acid
    [2889] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2-methoxyphenylthio) ethyl] Piperidine-4-hydroxysamic acid
    [2890] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (2-methoxyphenylthio) propyl] Piperidine-4-hydroxysamic acid
    [2891] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (3-methoxyphenylthio) ethyl] Piperidine-4-hydroxysamic acid
    [2892] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-methoxyphenylthio) propyl] Piperidine-4-hydroxysamic acid
    [2893] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (4-methoxyphenylthio) ethyl] Piperidine-4-hydroxysamic acid
    [2894] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-methoxyphenylthio) propyl] Piperidine-4-hydroxysamic acid
    [2895] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [cyclopentylmethyl] piperidine-4-hydroxy Samsan
    [2896] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (cyclopentyl) ethyl] piperidine- 4-hydroxysamic acid
    [2897] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (cyclohexyl) ethyl] piperidine- 4-hydroxysamic acid
    [2898] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (cyclopentylthio) ethyl] piperidine 4-hydroxysamic acid
    [2899] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (cyclopentylthio) propyl] piperidine 4-hydroxysamic acid
    [2900] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (cyclohexylthio) propyl] piperidine 4-hydroxysamic acid
    [2901] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (pyrid-2-yl) thioethyl ] Piperidine-4-hydroxysamic acid
    [2902] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [4- (thien-2-yl) butyl] py Ferridine-4-hydroxysamic acid
    [2903] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (thien-2-yl) thiopropyl] Piperidine-4-hydroxysamic acid
    [2904] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (thien-3-yl) propyl] py Ferridine-4-hydroxysamic acid
    [2905] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [4- (thien-3-yl) butyl] py Ferridine-4-hydroxysamic acid
    [2906] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (thien-2-yl) thioethyl] Piperidine-4-hydroxysamic acid
    [2907] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (thien-3-yl) thioethyl] Piperidine-4-hydroxysamic acid
    [2908] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (thien-3-yl) thiopropyl] Piperidine-4-hydroxysamic acid
    [2909] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (1,3-thiazole-2- I) propyl] piperidine-4- hydroxamic acid
    [2910] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [4- (1,3-thiazole-2- I) butyl] piperidine-4-hydroxysamic acid
    [2911] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (1,3-thiazole-2- Yl) thioethyl] piperidine-4-hydroxysamic acid
    [2912] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrid-2-yl) propyl] Piperidine-4-hydroxysamic acid
    [2913] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [4- (pyrid-2-yl) butyl] Piperidine-4-hydroxysamic acid
    [2914] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrid-2-yl) thiopropyl ] Piperidine-4-hydroxysamic acid
    [2915] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrid-3-yl) propyl] Piperidine-4-hydroxysamic acid
    [2916] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [4- (pyrid-3-yl) butyl] Piperidine-4-hydroxysamic acid
    [2917] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (pyrid-3-yl) thioethyl ] Piperidine-4-hydroxysamic acid
    [2918] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrid-3-yl) thiopropyl ] Piperidine-4-hydroxysamic acid
    [2919] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrid-4-yl) propyl] Piperidine-4-hydroxysamic acid
    [2920] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [4- (pyrid-4-yl) butyl] Piperidine-4-hydroxysamic acid
    [2921] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (pyrid-4-yl) thioethyl ] Piperidine-4-hydroxysamic acid
    [2922] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrid-4-yl) thiopropyl ] Piperidine-4-hydroxysamic acid
    [2923] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrazin-2-yl) propyl] py Ferridine-4-hydroxysamic acid
    [2924] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [4- (pyrazin-2-yl) butyl] py Ferridine-4-hydroxysamic acid
    [2925] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (pyrazin-2-yl) thioethyl] Piperidine-4-hydroxysamic acid
    [2926] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrazin-2-yl) thiopropyl] Piperidine-4-hydroxysamic acid
    [2927] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-fluorophenyl) prop- 2-ynyl] piperidine-4-hydroxysamic acid
    [2928] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (3,4-difluorophenyl) Prop-2-ynyl] piperidine-4-hydroxysamic acid
    [2929] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,4-difluorophenyl) Prop-2-ynyl] piperidine-4-hydroxysamic acid
    [2930] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,3,5-trifluoro Phenyl) prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [2931] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,4,6-trifluoro Phenyl) prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [2932] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (3,4,5-trifluoro Phenyl) prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [2933] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-chloro-3-fluorophenyl Prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [2934] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-chloro-4-fluorophenyl Prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [2935] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (2-chloro-4-fluorophenyl Prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [2936] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-chloro-5-fluorophenyl Prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [2937] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-chloro-2-fluorophenyl Prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [2938] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-fluoro-4-methylphenyl) Prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [2939] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (3,5-bistrifluoromethylphenyl Prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [2940] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (thien-2-yl) prop- 2-ynyl] piperidine-4-hydroxysamic acid
    [2941] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (thien-3-yl) prop- 2-ynyl] piperidine-4-hydroxysamic acid
    [2942] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (1,3-thiazole-2- Yl) prop-2-ynyl] piperidine-4-hydroxysamic acid
    [2943] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (1,3-thiazole-4- Yl) prop-2-ynyl] piperidine-4-hydroxysamic acid
    [2944] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (1,3-thiazole-5- Yl) prop-2-ynyl] piperidine-4-hydroxysamic acid
    [2945] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrid-2-yl) prop -2-ynyl] piperidine-4-hydroxysamic acid
    [2946] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrid-3-yl) prop -2-ynyl] piperidine-4-hydroxysamic acid
    [2947] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrid-4-yl) prop -2-ynyl] piperidine-4-hydroxysamic acid
    [2948] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) -propyl] -1- [2- (cyclohexyl) ethyl] piperidine- 4-hydroxysamic acid
    [2949] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) -propyl] -1- [3- (phenyl) propyl] piperidine-4 Hydroxamic acid
    [2950] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,3,5-trifluoro Phenyl) propyl] piperidine-4-hydroxysamic acid
    [2951] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) -propyl] -1- [2- (3,5-difluorophenylamino Ethyl] piperidine-4-hydroxysamic acid
    [2952] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2,3,5-trifluoro Phenylamino) ethyl] -piperidine-4-hydroxysamic acid
    [2953] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) -propyl] -1- [2- (3,5-difluorophenoxy Ethyl] piperidine-4-hydroxysamic acid
    [2954] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2,3,5-trifluoro Phenoxy) ethyl] piperidine-4-hydroxysamic acid
    [2955] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2,3,5-trifluoro Phenylthio) ethyl] piperidine-4-hydroxysamic acid
    [2956] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) -propyl] -1- [2- (cyclopentylthio) ethyl] piperidine 4-hydroxysamic acid
    [2957] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) -propyl] -1- [2- (pyrid-2-yl) thioethyl ] Piperidine-4-hydroxysamic acid
    [2958] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) -propyl] -1- [2- (thien-2-yl) thioethyl] Piperidine-4-hydroxysamic acid
    [2959] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,3,5-trifluoro Phenyl) prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [2960] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) -propyl] -1- [3- (thien-2-yl) prop- 2-ynyl] piperidine-4-hydroxysamic acid
    [2961] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (cyclohexyl) ethyl] piperidine 4-hydroxysamic acid
    [2962] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (phenyl) propyl] piperidine- 4-hydroxysamic acid
    [2963] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,3,5-trifluoro Lophenyl) propyl] piperidine-4-hydroxysamic acid
    [2964] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (3,5-difluorophenyl Amino) ethyl] piperidine-4-hydroxysamic acid
    [2965] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2,3,5-trifluoro Lophenylamino) ethyl] -piperidine-4-hydroxysamic acid
    [2966] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (3,5-difluorophenoxy Ethyl) piperidine-4-hydroxysamic acid
    [2967] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2,3,5-trifluoro Lofenoxy) ethyl] piperidine-4-hydroxysamic acid
    [2968] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2,3,5-trifluoro Rophenylthio) ethyl] -piperidine-4-hydroxysamic acid
    [2969] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (cyclopentylthio) ethyl] piperi Din-4-hydroxysamic acid
    [2970] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (pyrid-2-yl) thio Ethyl] piperidine-4-hydroxysamic acid
    [2971] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (thien-2-yl) thioethyl ] Piperidine-4-hydroxysamic acid
    [2972] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,3,5-trifluoro Lophenyl) prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [2973] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (thien-2-yl) prop -2-ynyl] piperidine-4-hydroxysamic acid
    [2974] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine- 4-hydroxysamic acid
    [2975] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine-4 Hydroxamic acid
    [2976] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Phenyl) -propyl] piperidine-4-hydroxysamic acid
    [2977] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino ) -Ethyl] piperidine-4-hydroxysamic acid
    [2978] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenyl-amino) ethyl] piperidine-4-hydroxysamic acid
    [2979] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy Ethyl] piperidine-4-hydroxysamic acid
    [2980] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenoxy) ethyl] -piperidine-4-hydroxysamic acid
    [2981] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenylthio) -ethyl] piperidine-4-hydroxysamic acid
    [2982] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine 4-hydroxysamic acid
    [2983] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl ] Piperidine-4-hydroxysamic acid
    [2984] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] Piperidine-4-hydroxysamic acid
    [2985] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Phenyl) prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [2986] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop- 2-ynyl] piperidine-4-hydroxysamic acid
    [2987] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine 4-hydroxysamic acid
    [2988] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine- 4-hydroxysamic acid
    [2989] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Lophenyl) -propyl] piperidine-4-hydroxysamic acid
    [2990] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenyl Amino) ethyl] -piperidine-4-hydroxysamic acid
    [2991] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Lophenylamino) ethyl] -piperidine-4-hydroxysamic acid
    [2992] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy Ethyl) piperidine-4-hydroxysamic acid
    [2993] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Lofenoxy) -ethyl] piperidine-4-hydroxysamic acid
    [2994] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Rophenylthio) -ethyl] piperidine-4-hydroxysamic acid
    [2995] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperi Din-4-hydroxysamic acid
    [2996] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thio Ethyl] piperidine-4-hydroxysamic acid
    [2997] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl ] Piperidine-4-hydroxysamic acid
    [2998] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Lophenyl) prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [2999] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop -2-ynyl] piperidine-4-hydroxysamic acid
    [3000] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine 4-hydroxysamic acid
    [3001] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine- 4-hydroxysamic acid
    [3002] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Lophenyl) propyl] piperidine-4-hydroxysamic acid
    [3003] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenyl Amino) ethyl] -piperidine-4-hydroxysamic acid
    [3004] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Lophenylamino) ethyl] -piperidine-4-hydroxysamic acid
    [3005] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy Ethyl) piperidine-4-hydroxysamic acid
    [3006] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Lofenoxy) ethyl] piperidine-4-hydroxysamic acid
    [3007] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Rophenylthio) ethyl] -piperidine-4-hydroxysamic acid
    [3008] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperi Din-4-hydroxysamic acid
    [3009] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thio Ethyl] piperidine-4-hydroxysamic acid
    [3010] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl ] Piperidine-4-hydroxysamic acid
    [3011] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Lophenyl) prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [3012] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop -2-ynyl] piperidine-4-hydroxysamic acid
    [3013] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine- 4-hydroxysamic acid
    [3014] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine-4 Hydroxamic acid
    [3015] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Phenyl) propyl] piperidine-4-hydroxysamic acid
    [3016] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino Ethyl] -piperidine-4-hydroxysamic acid
    [3017] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenylamino) ethyl] -piperidine-4-hydroxysamic acid
    [3018] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy Ethyl] piperidine-4-hydroxysamic acid
    [3019] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenoxy) ethyl] piperidine-4-hydroxysamic acid
    [3020] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenylthio) ethyl] -piperidine-4-hydroxysamic acid
    [3021] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine 4-hydroxysamic acid
    [3022] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl ] Piperidine-4-hydroxysamic acid
    [3023] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] Piperidine-4-hydroxysamic acid
    [3024] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Phenyl) prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [3025] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop- 2-ynyl] piperidine-4-hydroxysamic acid
    [3026] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxy-quinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] py Ferridine-4-hydroxysamic acid
    [3027] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxy-quinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperi Din-4-hydroxysamic acid
    [3028] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxy-quinolin-4-yl) propyl] -1- [3- (2,3,5- Trifluorophenyl) -propyl] piperidine-4-hydroxysamic acid
    [3029] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxy-quinolin-4-yl) propyl] -1- [2- (3,5-difluoro Lophenylamino) -ethyl] piperidine-4-hydroxysamic acid
    [3030] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxy-quinolin-4-yl) propyl] -1- [2- (2,3,5- Trifluorophenyl-amino) ethyl] piperidine-4-hydroxysamic acid
    [3031] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxy-quinolin-4-yl) propyl] -1- [2- (3,5-difluoro Lofenoxy) -ethyl] piperidine-4-hydroxysamic acid
    [3032] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxy-quinolin-4-yl) propyl] -1- [2- (2,3,5- Trifluorophenoxy) -ethyl] piperidine-4-hydroxysamic acid
    [3033] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxy-quinolin-4-yl) propyl] -1- [2- (2,3,5- Trifluorophenylthio) -ethyl] piperidine-4-hydroxysamic acid
    [3034] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxy-quinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] Piperidine-4-hydroxysamic acid
    [3035] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxy-quinolin-4-yl) propyl] -1- [2- (pyrid-2-yl ) Thioethyl] -piperidine-4-hydroxysamic acid
    [3036] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxy-quinolin-4-yl) propyl] -1- [2- (thien-2-yl) Thioethyl] -piperidine-4-hydroxysamic acid
    [3037] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxy-quinolin-4-yl) propyl] -1- [3- (2,3,5- Trifluorophenyl) prop-2-ynyl] piperidine-4-hydroxysamic acid
    [3038] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxy-quinolin-4-yl) propyl] -1- [3- (thien-2-yl) Prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [3039] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,4,6-trifluoro Phenyl) propyl] piperidine-4-hydroxysamic acid
    [3040] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) -propyl] -1- [3- (3,4,5-trifluoro Phenyl) propyl] piperidine-4-hydroxysamic acid
    [3041] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2,4,6-trifluoro Phenylthio) ethyl] piperidine-4-hydroxysamic acid
    [3042] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) -propyl] -1- [2- (3,4,5-trifluoro Phenylthio) ethyl] piperidine-4-hydroxysamic acid
    [3043] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2,4,6-trifluoro Phenylamino) ethyl] -piperidine-4-hydroxysamic acid
    [3044] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) -propyl] -1- [2- (3,4,5-trifluoro Phenylamino) ethyl] -piperidine-4-hydroxysamic acid
    [3045] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2,4,6-trifluoro Phenoxy) ethyl] piperidine-4-hydroxysamic acid
    [3046] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) -propyl] -1- [2- (3,4,5-trifluoro Phenoxy) ethyl] piperidine-4-hydroxysamic acid
    [3047] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,4,6-trifluoro Phenyl) prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [3048] 4- [3- (R, S) -hydroxy-3- (3-methyl-6-methoxyquinolin-4-yl) -propyl] -1- [3- (3,4,5-trifluoro Phenyl) prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [3049] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,4,6-trifluoro Lophenyl) propyl] piperidine-4-hydroxysamic acid
    [3050] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (3,4,5-trifluoro Lophenyl) propyl] piperidine-4-hydroxysamic acid
    [3051] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2,4,6-trifluoro Rophenylthio) ethyl] piperidine-4-hydroxysamic acid
    [3052] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (3,4,5-trifluoro Rophenylthio) ethyl] piperidine-4-hydroxysamic acid
    [3053] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2,4,6-trifluoro Lophenylamino) ethyl] -piperidine-4-hydroxysamic acid
    [3054] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (3,4,5-trifluoro Lophenylamino) ethyl] -piperidine-4-hydroxysamic acid
    [3055] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2,4,6-trifluoro Lofenoxy) ethyl] piperidine-4-hydroxysamic acid
    [3056] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (3,4,5-trifluoro Lofenoxy) ethyl] piperidine-4-hydroxysamic acid
    [3057] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,4,6-trifluoro Lophenyl) prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [3058] 4- [3- (R, S) -hydroxy-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (3,4,5-trifluoro Lophenyl) prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [3059] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) propyl] -piperidine-4-hydroxysamic acid
    [3060] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Phenyl) propyl] -piperidine-4-hydroxysamic acid
    [3061] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenylthio) -ethyl] piperidine-4-hydroxysamic acid
    [3062] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenylthio) ethyl] -piperidine-4-hydroxysamic acid
    [3063] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenylamino) ethyl] -piperidine-4-hydroxysamic acid
    [3064] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenyl-amino) ethyl] piperidine-4-hydroxysamic acid
    [3065] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenoxy) -ethyl] piperidine-4-hydroxysamic acid
    [3066] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenoxy) -ethyl] piperidine-4-hydroxysamic acid
    [3067] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [3068] 4- [3- (R, S) -hydroxy-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Phenyl) prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [3069] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Lophenyl) -propyl] piperidine-4-hydroxysamic acid
    [3070] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Rophenylthio) -ethyl] piperidine-4-hydroxysamic acid
    [3071] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Rophenylthio) -ethyl] piperidine-4-hydroxysamic acid
    [3072] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Rophenyl-amino) ethyl] piperidine-4-hydroxysamic acid
    [3073] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Rophenyl-amino) ethyl] piperidine-4-hydroxysamic acid
    [3074] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Lofenoxy) -ethyl] piperidine-4-hydroxysamic acid
    [3075] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Lofenoxy) -ethyl] piperidine-4-hydroxysamic acid
    [3076] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Lophenyl) prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [3077] 4- [3- (R, S) -hydroxy-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Lophenyl) prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [3078] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Lophenyl) propyl] piperidine-4-hydroxysamic acid
    [3079] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Lophenyl) propyl] piperidine-4-hydroxysamic acid
    [3080] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Rophenylthio) ethyl] -piperidine-4-hydroxysamic acid
    [3081] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Rophenylthio) ethyl] -piperidine-4-hydroxysamic acid
    [3082] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Lophenylamino) ethyl] -piperidine-4-hydroxysamic acid
    [3083] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Lophenylamino) ethyl] -piperidine-4-hydroxysamic acid
    [3084] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Lofenoxy) ethyl] piperidine-4-hydroxysamic acid
    [3085] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Lofenoxy) ethyl] piperidine-4-hydroxysamic acid
    [3086] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Lophenyl) prop-2-ynyl] piperidine-4-hydroxysamic acid
    [3087] 4- [3- (R, S) -hydroxy-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Lophenyl) prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [3088] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) propyl] piperidine-4-hydroxysamic acid
    [3089] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Phenyl) propyl] piperidine-4-hydroxysamic acid
    [3090] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenylthio) ethyl] -piperidine-4-hydroxysamic acid
    [3091] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenylthio) ethyl] -piperidine-4-hydroxysamic acid
    [3092] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenylamino) ethyl] -piperidine-4-hydroxysamic acid
    [3093] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenylamino) ethyl] -piperidine-4-hydroxysamic acid
    [3094] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenoxy) ethyl] piperidine-4-hydroxysamic acid
    [3095] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenoxy) ethyl] piperidine-4-hydroxysamic acid
    [3096] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [3097] 4- [3- (R, S) -hydroxy-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Phenyl) prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [3098] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxy-quinolin-4-yl) propyl] -1- [3- (2,4,6- Trifluorophenyl) -propyl] piperidine-4-hydroxysamic acid
    [3099] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxy-quinolin-4-yl) propyl] -1- [3- (3,4,5- Trifluorophenyl) -propyl] piperidine-4-hydroxysamic acid
    [3100] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxy-quinolin-4-yl) propyl] -1- [2- (2,4,6- Trifluorophenylthio) -ethyl] piperidine-4-hydroxysamic acid
    [3101] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxy-quinolin-4-yl) propyl] -1- [2- (3,4,5- Trifluorophenylthio) -ethyl] piperidine-4-hydroxysamic acid
    [3102] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxy-quinolin-4-yl) propyl] -1- [2- (2,4,6- Trifluorophenyl-amino) ethyl] piperidine-4-hydroxysamic acid
    [3103] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxy-quinolin-4-yl) propyl] -1- [2- (3,4,5- Trifluorophenyl-aminoethyl] piperidine-4-hydroxysamic acid
    [3104] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxy-quinolin-4-yl) propyl] -1- [2- (2,4,6- Trifluorophenoxy) -ethyl] piperidine-4-hydroxysamic acid
    [3105] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxy-quinolin-4-yl) propyl] -1- [2- (3,4,5- Trifluorophenoxy) -ethyl] piperidine-4-hydroxysamic acid
    [3106] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxy-quinolin-4-yl) propyl] -1- [3- (2,4,6- Trifluorophenyl) prop-2-ynyl] piperidine-4-hydroxysamic acid
    [3107] 4- [3- (R, S) -hydroxy-3- (3-morpholinomethyl-6-methoxy-quinolin-4-yl) propyl] -1- [3- (3,4,5- Trifluorophenyl) prop-2-ynyl] piperidine-4-hydroxysamic acid
    [3108] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1-heptylpiperidine-4-hydroxysamic acid
    [3109] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [4-phenylbutyl] piperidine-4-hydro Roksamsan
    [3110] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (phenyl) propyl] piperidine-4 Hydroxamic acid
    [3111] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [4- (2-fluorophenyl) propyl] py Ferridine-4-hydroxysamic acid
    [3112] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [4- (3-fluorophenyl) propyl] py Ferridine-4-hydroxysamic acid
    [3113] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- (3- (4-fluorophenyl) propyl] py Ferridine-4-hydroxysamic acid
    [3114] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [4- (4-fluorophenyl) butyl] py Ferridine-4-hydroxysamic acid
    [3115] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,3-difluorophenyl) Propyl] piperidine-4-hydroxysamic acid
    [3116] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [4- (2,3-difluorophenyl) Propyl] piperidine-4-hydroxysamic acid
    [3117] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,6-difluorophenyl) Propyl] piperidine-4-hydroxysamic acid
    [3118] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [4- (2,6-difluorophenyl) Propyl] piperidine-4-hydroxysamic acid
    [3119] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (3,5-difluorophenyl) Propyl] piperidine-4-hydroxysamic acid
    [3120] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,3,5-trifluoro Phenyl) propyl] piperidine-4-hydroxysamic acid
    [3121] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,4,6-trifluoro Phenyl) propyl] piperidine-4-hydroxysamic acid
    [3122] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (3,4,5-trifluoro Phenyl) propyl] piperidine-4-hydroxysamic acid
    [3123] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3-phenylthiopropyl] piperidine-4- Hydroxamic acid
    [3124] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (2-fluorophenylthio) propyl] Piperidine-4-hydroxysamic acid
    [3125] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-fluorophenylthio) propyl] Piperidine-4-hydroxysamic acid
    [3126] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (4-fluorophenylthio) ethyl] Piperidine-4-hydroxysamic acid
    [3127] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-fluorophenylthio) propyl] Piperidine-4-hydroxysamic acid
    [3128] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2,3-difluorophenylthio Ethyl] piperidine-4-hydroxysamic acid
    [3129] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,3-difluorophenylthio ) Propyl] piperidine-4-hydroxysamic acid
    [3130] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2,6-difluorophenylthio Ethyl] piperidine-4-hydroxysamic acid
    [3131] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2,3,5-trifluoro Phenylthio) ethyl] piperidine-4-hydroxysamic acid
    [3132] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2,4,6-trifluoro Phenylthio) ethyl] piperidine-4-hydroxysamic acid
    [3133] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (3,4,5-trifluoro Phenylthio) ethyl] piperidine-4-hydroxysamic acid
    [3134] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (3,5-difluorophenoxy Ethyl] piperidine-4-hydroxysamic acid
    [3135] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2,3,5-trifluoro Phenoxy) ethyl] piperidine-4-hydroxysamic acid
    [3136] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2,4,6-trifluoro Phenoxy) ethyl] piperidine-4-hydroxysamic acid
    [3137] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (3,4,5-trifluoro Phenoxy) ethyl] piperidine-4-hydroxysamic acid
    [3138] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (3,5-difluorophenylamino Ethyl] piperidine-4-hydroxysamic acid
    [3139] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2,3,5-trifluoro Phenylamino) ethyl] -piperidine-4-hydroxysamic acid
    [3140] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2,4,6-trifluoro Phenylamino) ethyl] -piperidine-4-hydroxysamic acid
    [3141] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (3,4,5-trifluoro Phenylamino) ethyl] -piperidine-4-hydroxysamic acid
    [3142] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,6-difluorophenylthio ) Propyl] piperidine-4-hydroxysamic acid
    [3143] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2-chlorophenylthio) ethyl] pi Ferridine-4-hydroxysamic acid
    [3144] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (2-chlorophenylthio) propyl] py Ferridine-4-hydroxysamic acid
    [3145] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (3-chlorophenylthio) ethyl] py Ferridine-4-hydroxysamic acid
    [3146] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-chlorophenylthio) propyl] py Ferridine-4-hydroxysamic acid
    [3147] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (4-chlorophenylthio) ethyl] pi Ferridine-4-hydroxysamic acid
    [3148] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-chlorophenylthio) propyl] py Ferridine-4-hydroxysamic acid
    [3149] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2-methylphenylthio) ethyl] piperi Din-4-hydroxysamic acid
    [3150] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (2-methylphenylthio) propyl] piperi Din-4-hydroxysamic acid
    [3151] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (3-methylphenylthio) ethyl] piperi Din-4-hydroxysamic acid
    [3152] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-methylphenylthio) propyl] piperi Din-4-hydroxysamic acid
    [3153] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (4-methylphenylthio) ethyl] piperi Din-4-hydroxysamic acid
    [3154] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-methylphenylthio) propyl] piperi Din-4-hydroxysamic acid
    [3155] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2-trifluoromethylphenylthio) ethyl ] -Piperidine-4-hydroxysamic acid
    [3156] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (2-trifluoromethylphenylthio) propyl ] -Piperidine-4-hydroxysamic acid
    [3157] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (3-trifluoromethylphenylthio) ethyl ] -Piperidine-4-hydroxysamic acid
    [3158] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-trifluoromethylphenylthio) propyl ] -Piperidine-4-hydroxysamic acid
    [3159] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (4-trifluoromethylphenylthio) ethyl ] -Piperidine-4-hydroxysamic acid
    [3160] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-trifluoromethylphenylthio) propyl ] -Piperidine-4-hydroxysamic acid
    [3161] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2-methoxyphenylthio) ethyl] Piperidine-4-hydroxysamic acid
    [3162] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (2-methoxyphenylthio) propyl] Piperidine-4-hydroxysamic acid
    [3163] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (3-methoxyphenylthio) ethyl] Piperidine-4-hydroxysamic acid
    [3164] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-methoxyphenylthio) propyl] Piperidine-4-hydroxysamic acid
    [3165] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (4-methoxyphenylthio) ethyl] Piperidine-4-hydroxysamic acid
    [3166] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-methoxyphenylthio) propyl] Piperidine-4-hydroxysamic acid
    [3167] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [cyclopentylmethyl] piperidine-4-hydroxy Samsan
    [3168] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (cyclopentyl) ethyl] piperidine- 4-hydroxysamic acid
    [3169] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (cyclohexyl) ethyl] piperidine- 4-hydroxysamic acid
    [3170] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (cyclopentylthio) ethyl] piperidine 4-hydroxysamic acid
    [3171] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (cyclopentylthio) propyl] piperidine 4-hydroxysamic acid
    [3172] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (cyclohexylthio) propyl] piperidine 4-hydroxysamic acid
    [3173] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (pyrid-2-yl) thioethyl ] Piperidine-4-hydroxysamic acid
    [3174] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [4- (thien-2-yl) butyl] py Ferridine-4-hydroxysamic acid
    [3175] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (thien-2-yl) thiopropyl] Piperidine-4-hydroxysamic acid
    [3176] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (thien-3-yl) propyl] py Ferridine-4-hydroxysamic acid
    [3177] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [4- (thien-3-yl) butyl] py Ferridine-4-hydroxysamic acid
    [3178] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (thien-2-yl) thioethyl] Piperidine-4-hydroxysamic acid
    [3179] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (thien-3-yl) thioethyl] Piperidine-4-hydroxysamic acid
    [3180] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (thien-3-yl) thiopropyl] Piperidine-4-hydroxysamic acid
    [3181] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (1,3-thiazole-2- I) propyl] piperidine-4- hydroxamic acid
    [3182] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [4- (1,3-thiazole-2- I) butyl] piperidine-4-hydroxysamic acid
    [3183] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (1,3-thiazole-2- Yl) thioethyl] piperidine-4-hydroxysamic acid
    [3184] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrid-2-yl) propyl] Piperidine-4-hydroxysamic acid
    [3185] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [4- (pyrid-2-yl) butyl] Piperidine-4-hydroxysamic acid
    [3186] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrid-2-yl) thiopropyl ] Piperidine-4-hydroxysamic acid
    [3187] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrid-3-yl) propyl] Piperidine-4-hydroxysamic acid
    [3188] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [4- (pyrid-3-yl) butyl] Piperidine-4-hydroxysamic acid
    [3189] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (pyrid-3-yl) thioethyl ] Piperidine-4-hydroxysamic acid
    [3190] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrid-3-yl) thiopropyl ] Piperidine-4-hydroxysamic acid
    [3191] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrid-4-yl) propyl] Piperidine-4-hydroxysamic acid
    [3192] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [4- (pyrid-4-yl) butyl] Piperidine-4-hydroxysamic acid
    [3193] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (pyrid-4-yl) thioethyl ] Piperidine-4-hydroxysamic acid
    [3194] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrid-4-yl) thiopropyl ] Piperidine-4-hydroxysamic acid
    [3195] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrazin-2-yl) propyl] py Ferridine-4-hydroxysamic acid
    [3196] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [4- (pyrazin-2-yl) butyl] py Ferridine-4-hydroxysamic acid
    [3197] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (pyrazin-2-yl) thioethyl] Piperidine-4-hydroxysamic acid
    [3198] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrazin-2-yl) thiopropyl] Piperidine-4-hydroxysamic acid
    [3199] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-fluorophenyl) prop- 2-ynyl] piperidine-4-hydroxysamic acid
    [3200] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (3,4-difluorophenyl) Prop-2-ynyl] piperidine-4-hydroxysamic acid
    [3201] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,4-difluorophenyl) Prop-2-ynyl] piperidine-4-hydroxysamic acid
    [3202] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,3,5-trifluoro Phenyl) prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [3203] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,4,6-trifluoro Phenyl) prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [3204] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (3,4,5-trifluoro Phenyl) prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [3205] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-chloro-3-fluorophenyl Prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [3206] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-chloro-4-fluorophenyl Prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [3207] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (2-chloro-4-fluorophenyl Prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [3208] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-chloro-5-fluorophenyl Prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [3209] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (4-chloro-2-fluorophenyl Prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [3210] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (3-fluoro-4-methylphenyl) Prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [3211] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (3,5-bistrifluoromethylphenyl ) Prop-2-ynyl] piperidine-4-hydroxysamic acid
    [3212] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (thien-2-yl) prop- 2-ynyl] piperidine-4-hydroxysamic acid
    [3213] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (thien-3-yl) prop- 2-ynyl] piperidine-4-hydroxysamic acid
    [3214] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (1,3-thiazole-2- Yl) prop-2-ynyl] piperidine-4-hydroxysamic acid
    [3215] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (1,3-thiazole-4- Yl) prop-2-ynyl] piperidine-4-hydroxysamic acid
    [3216] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (1,3-thiazole-5- Yl) prop-2-ynyl] piperidine-4-hydroxysamic acid
    [3217] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrid-2-yl) prop -2-ynyl] piperidine-4-hydroxysamic acid
    [3218] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrid-3-yl) prop -2-ynyl] piperidine-4-hydroxysamic acid
    [3219] 4- [3- (R, S) -Fluoro-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (pyrid-4-yl) prop -2-ynyl] piperidine-4-hydroxysamic acid
    [3220] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) -propyl] -1- [2- (cyclohexyl) ethyl] piperidine- 4-hydroxysamic acid
    [3221] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) -propyl] -1- [3- (phenyl) propyl] piperidine-4 Hydroxamic acid
    [3222] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,3,5-trifluoro Phenyl) propyl] piperidine-4-hydroxysamic acid
    [3223] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) -propyl] -1- [2- (3,5-difluorophenylamino Ethyl] piperidine-4-hydroxysamic acid
    [3224] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2,3,5-trifluoro Phenylamino) ethyl] -piperidine-4-hydroxysamic acid
    [3225] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) -propyl] -1- [2- (3,5-difluorophenoxy Ethyl] piperidine-4-hydroxysamic acid
    [3226] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2,3,5-trifluoro Phenoxy) ethyl] piperidine-4-hydroxysamic acid
    [3227] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2,3,5-trifluoro Phenylthio) ethyl] piperidine-4-hydroxysamic acid
    [3228] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) -propyl] -1- [2- (cyclopentylthio) ethyl] piperidine 4-hydroxysamic acid
    [3229] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) -propyl] -1- [2- (pyrid-2-yl) thioethyl ] Piperidine-4-hydroxysamic acid
    [3230] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) -propyl] -1- [2- (thien-2-yl) thioethyl] Piperidine-4-hydroxysamic acid
    [3231] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,3,5-trifluoro Phenyl) prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [3232] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) -propyl] -1- [3- (thien-2-yl) prop- 2-ynyl] piperidine-4-hydroxysamic acid
    [3233] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (cyclohexyl) ethyl] piperidine 4-hydroxysamic acid
    [3234] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (phenyl) propyl] piperidine- 4-hydroxysamic acid
    [3235] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,3,5-trifluoro Lophenyl) propyl] piperidine-4-hydroxysamic acid
    [3236] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (3,5-difluorophenyl Amino) ethyl] piperidine-4-hydroxysamic acid
    [3237] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2,3,5-trifluoro Lophenylamino) ethyl] -piperidine-4-hydroxysamic acid
    [3238] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (3,5-difluorophenoxy Ethyl) piperidine-4-hydroxysamic acid
    [3239] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2,3,5-trifluoro Lofenoxy) ethyl] piperidine-4-hydroxysamic acid
    [3240] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2,3,5-trifluoro Rophenylthio) ethyl] piperidine-4-hydroxysamic acid
    [3241] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (cyclopentylthio) ethyl] piperi Din-4-hydroxysamic acid
    [3242] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (pyrid-2-yl) thio Ethyl] piperidine-4-hydroxysamic acid
    [3243] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (thien-2-yl) thioethyl ] Piperidine-4-hydroxysamic acid
    [3244] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,3,5-trifluoro Lophenyl) prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [3245] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (thien-2-yl) prop -2-ynyl] piperidine-4-hydroxysamic acid
    [3246] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine- 4-hydroxysamic acid
    [3247] 4- [3- (R, S) -fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine-4 Hydroxamic acid
    [3248] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Phenyl) propyl] piperidine-4-hydroxysamic acid
    [3249] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino Ethyl] -piperidine-4-hydroxysamic acid
    [3250] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenylamino) ethyl] -piperidine-4-hydroxysamic acid
    [3251] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy Ethyl] piperidine-4-hydroxysamic acid
    [3252] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenoxy) ethyl] piperidine-4-hydroxysamic acid
    [3253] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenylthio) ethyl] -piperidine-4-hydroxysamic acid
    [3254] 4- [3- (R, S) -fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine 4-hydroxysamic acid
    [3255] 4- [3- (R, S) -fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl ] Piperidine-4-hydroxysamic acid
    [3256] 4- [3- (R, S) -fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] Piperidine-4-hydroxysamic acid
    [3257] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Phenyl) prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [3258] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop- 2-ynyl] piperidine-4-hydroxysamic acid
    [3259] 4- [3- (R, S) -fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine 4-hydroxysamic acid
    [3260] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine- 4-hydroxysamic acid
    [3261] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Lophenyl) propyl] piperidine-4-hydroxysamic acid
    [3262] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenyl Amino) ethyl] -piperidine-4-hydroxysamic acid
    [3263] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Lophenylamino) ethyl] -piperidine-4-hydroxysamic acid
    [3264] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy Ethyl) piperidine-4-hydroxysamic acid
    [3265] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Lofenoxy) ethyl] piperidine-4-hydroxysamic acid
    [3266] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Rophenylthio) ethyl] -piperidine-4-hydroxysamic acid
    [3267] 4- [3- (R, S) -fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperi Din-4-hydroxysamic acid
    [3268] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thio Ethyl] piperidine-4-hydroxysamic acid
    [3269] 4- [3- (R, S) -fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl ] Piperidine-4-hydroxysamic acid
    [3270] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Lophenyl) prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [3271] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop -2-ynyl] piperidine-4-hydroxysamic acid
    [3272] 4- [3- (R, S) -fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine 4-hydroxysamic acid
    [3273] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine- 4-hydroxysamic acid
    [3274] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Lophenyl) propyl] piperidine-4-hydroxysamic acid
    [3275] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenyl Amino) ethyl] -piperidine-4-hydroxysamic acid
    [3276] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Lophenylamino) ethyl] -piperidine-4-hydroxysamic acid
    [3277] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy Ethyl] piperidine-4-hydroxysamic acid
    [3278] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Lofenoxy) ethyl] piperidine-4-hydroxysamic acid
    [3279] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Rophenylthio) ethyl] -piperidine-4-hydroxysamic acid
    [3280] 4- [3- (R, S) -fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperi Din-4-hydroxysamic acid
    [3281] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thio Ethyl] piperidine-4-hydroxysamic acid
    [3282] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl ] Piperidine-4-hydroxysamic acid
    [3283] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Lophenyl) prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [3284] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop -2-ynyl] piperidine-4-hydroxysamic acid
    [3285] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] piperidine- 4-hydroxysamic acid
    [3286] 4- [3- (R, S) -fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperidine-4 Hydroxamic acid
    [3287] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Phenyl) propyl] piperidine-4-hydroxysamic acid
    [3288] 4- [3- (R, S) -fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino Ethyl] -piperidine-4-hydroxysamic acid
    [3289] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenylamino) ethyl] -piperidine-4-hydroxysamic acid
    [3290] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy Ethyl] piperidine-4-hydroxysamic acid
    [3291] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenoxy) ethyl] piperidine-4-hydroxysamic acid
    [3292] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro Phenylthio) ethyl] -piperidine-4-hydroxysamic acid
    [3293] 4- [3- (R, S) -fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine 4-hydroxysamic acid
    [3294] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl ] Piperidine-4-hydroxysamic acid
    [3295] 4- [3- (R, S) -fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] Piperidine-4-hydroxysamic acid
    [3296] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluoro Phenyl) prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [3297] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (thien-2-yl) prop- 2-ynyl] piperidine-4-hydroxysamic acid
    [3298] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxy-quinolin-4-yl) propyl] -1- [2- (cyclohexyl) ethyl] py Ferridine-4-hydroxysamic acid
    [3299] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxy-quinolin-4-yl) propyl] -1- [3- (phenyl) propyl] piperi Din-4-hydroxysamic acid
    [3300] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxy-quinolin-4-yl) propyl] -1- [3- (2,3,5- Trifluorophenyl) -propyl] piperidine-4-hydroxysamic acid
    [3301] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxy-quinolin-4-yl) propyl] -1- [2- (3,5-difluoro Lophenylamino) -ethyl] piperidine-4-hydroxysamic acid
    [3302] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxy-quinolin-4-yl) propyl] -1- [2- (2,3,5- Trifluorophenyl-aminoethyl] piperidine-4-hydroxysamic acid
    [3303] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxy-quinolin-4-yl) propyl] -1- [2- (3,5-difluoro Lofenoxy) -ethyl] piperidine-4-hydroxysamic acid
    [3304] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxy-quinolin-4-yl) propyl] -1- [2- (2,3,5- Trifluorophenoxy) -ethyl] piperidine-4-hydroxysamic acid
    [3305] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxy-quinolin-4-yl) propyl] -1- [2- (2,3,5- Trifluorophenyl-thio) ethyl] piperidine-4-hydroxysamic acid
    [3306] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxy-quinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] Piperidine-4-hydroxysamic acid
    [3307] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxy-quinolin-4-yl) propyl] -1- [2- (pyrid-2-yl ) Thioethyl] -piperidine-4-hydroxysamic acid
    [3308] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxy-quinolin-4-yl) propyl] -1- [2- (thien-2-yl) Thioethyl] -piperidine-4-hydroxysamic acid
    [3309] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxy-quinolin-4-yl) propyl] -1- [3- (2,3,5- Trifluorophenyl) prop-2-ynyl] piperidine-4-hydroxysamic acid
    [3310] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxy-quinolin-4-yl) propyl] -1- [3- (thien-2-yl) Prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [3311] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,4,6-trifluoro Phenyl) propyl] piperidine-4-hydroxysamic acid
    [3312] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) -propyl] -1- [3- (3,4,5-trifluoro Phenyl) propyl] piperidine-4-hydroxysamic acid
    [3313] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2,4,6-trifluoro Phenylthio) ethyl] piperidine-4-hydroxysamic acid
    [3314] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) -propyl] -1- [2- (3,4,5-trifluoro Phenylthio) ethyl] piperidine-4-hydroxysamic acid
    [3315] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2,4,6-trifluoro Phenylamino) ethyl] -piperidine-4-hydroxysamic acid
    [3316] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) -propyl] -1- [2- (3,4,5-trifluoro Phenylamino) ethyl] -piperidine-4-hydroxysamic acid
    [3317] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2,4,6-trifluoro Phenoxy) ethyl] piperidine-4-hydroxysamic acid
    [3318] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) -propyl] -1- [2- (3,4,5-trifluoro Phenoxy) ethyl] piperidine-4-hydroxysamic acid
    [3319] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,4,6-trifluoro Phenyl) prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [3320] 4- [3- (R, S) -Fluoro-3- (3-methyl-6-methoxyquinolin-4-yl) -propyl] -1- [3- (3,4,5-trifluoro Phenyl) prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [3321] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,4,6-trifluoro Lophenyl) propyl] piperidine-4-hydroxysamic acid
    [3322] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (3,4,5-trifluoro Lophenyl) propyl] piperidine-4-hydroxysamic acid
    [3323] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2,4,6-trifluoro Rophenylthio) ethyl] piperidine-4-hydroxysamic acid
    [3324] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (3,4,5-trifluoro Rophenylthio) ethyl] piperidine-4-hydroxysamic acid
    [3325] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2,4,6-trifluoro Lophenylamino) ethyl] -piperidine-4-hydroxysamic acid
    [3326] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (3,4,5-trifluoro Lophenylamino) ethyl] -piperidine-4-hydroxysamic acid
    [3327] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (2,4,6-trifluoro Lofenoxy) ethyl] piperidine-4-hydroxysamic acid
    [3328] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (3,4,5-trifluoro Lofenoxy) ethyl] piperidine-4-hydroxysamic acid
    [3329] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,4,6-trifluoro Lophenyl) prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [3330] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (3,4,5-trifluoro Lophenyl) prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [3331] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) propyl] piperidine-4-hydroxysamic acid
    [3332] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Phenyl) propyl] piperidine-4-hydroxysamic acid
    [3333] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenylthio) ethyl] -piperidine-4-hydroxysamic acid
    [3334] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenylthio) ethyl] -piperidine-4-hydroxysamic acid
    [3335] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenylamino) ethyl] -piperidine-4-hydroxysamic acid
    [3336] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenylamino) ethyl] -piperidine-4-hydroxysamic acid
    [3337] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenoxy) ethyl] piperidine-4-hydroxysamic acid
    [3338] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenoxy) ethyl] piperidine-4-hydroxysamic acid
    [3339] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [3340] 4- [3- (R, S) -Fluoro-3- (3-dimethylamino-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Phenyl) prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [3341] 4- [3- (R, S) -Fluoro-3- (3-fluoro-6-methoxyquinolin-4-yl) -propyl] -1- [3- (2,4,6-trifluoro Lophenyl) propyl] piperidine-4-hydroxysamic acid
    [3342] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Lophenyl) propyl] piperidine-4-hydroxysamic acid
    [3343] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Rophenylthio) ethyl] -piperidine-4-hydroxysamic acid
    [3344] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Rophenylthio) ethyl] -piperidine-4-hydroxysamic acid
    [3345] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Lophenylamino) ethyl] -piperidine-4-hydroxysamic acid
    [3346] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Lophenylamino) ethyl] -piperidine-4-hydroxysamic acid
    [3347] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Lofenoxy) ethyl] piperidine-4-hydroxysamic acid
    [3348] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Lofenoxy) ethyl] piperidine-4-hydroxysamic acid
    [3349] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Lophenyl) prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [3350] 4- [3- (R, S) -Fluoro-3- (3-hydroxymethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Lophenyl) prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [3351] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Lophenyl) propyl] piperidine-4-hydroxysamic acid
    [3352] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Lophenyl) propyl] piperidine-4-hydroxysamic acid
    [3353] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Rophenylthio) ethyl] -piperidine-4-hydroxysamic acid
    [3354] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Rophenylthio) ethyl] -piperidine-4-hydroxysamic acid
    [3355] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Lophenylamino) ethyl] -piperidine-4-hydroxysamic acid
    [3356] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Lophenylamino) ethyl] -piperidine-4-hydroxysamic acid
    [3357] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Lofenoxy) ethyl] piperidine-4-hydroxysamic acid
    [3358] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Lofenoxy) ethyl] piperidine-4-hydroxysamic acid
    [3359] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Lophenyl) prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [3360] 4- [3- (R, S) -Fluoro-3- (3-fluoromethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Lophenyl) prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [3361] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) propyl] piperidine-4-hydroxysamic acid
    [3362] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Phenyl) propyl] piperidine-4-hydroxysamic acid
    [3363] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenylthio) ethyl] -piperidine-4-hydroxysamic acid
    [3364] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenylthio) ethyl] -piperidine-4-hydroxysamic acid
    [3365] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenylamino) ethyl] -piperidine-4-hydroxysamic acid
    [3366] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenylamino) ethyl] -piperidine-4-hydroxysamic acid
    [3367] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,4,6-trifluoro Phenoxy) ethyl] piperidine-4-hydroxysamic acid
    [3368] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluoro Phenoxy) ethyl] piperidine-4-hydroxysamic acid
    [3369] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluoro Phenyl) prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [3370] 4- [3- (R, S) -Fluoro-3- (3-aminomethyl-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluoro Phenyl) prop-2-ynyl] -piperidine-4-hydroxysamic acid
    [3371] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxy-quinolin-4-yl) propyl] -1- [3- (2,4,6- Trifluorophenyl) -propyl] piperidine-4-hydroxysamic acid
    [3372] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxy-quinolin-4-yl) propyl] -1- [3- (3,4,5- Trifluorophenyl) -propyl] piperidine-4-hydroxysamic acid
    [3373] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxy-quinolin-4-yl) propyl] -1- [2- (2,4,6- Trifluorophenylthio) -ethyl] piperidine-4-hydroxysamic acid
    [3374] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxy-quinolin-4-yl) propyl] -1- [2- (3,4,5- Trifluorophenylthio) -ethyl] piperidine-4-hydroxysamic acid
    [3375] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxy-quinolin-4-yl) propyl] -1- [2- (2,4,6- Trifluorophenyl-aminoethyl] piperidine-4-hydroxysamic acid
    [3376] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxy-quinolin-4-yl) propyl] -1- [2- (3,4,5- Trifluorophenyl-aminoethyl] piperidine-4-hydroxysamic acid
    [3377] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxy-quinolin-4-yl) propyl] -1- [2- (2,4,6- Trifluorophenoxy) -ethyl] piperidine-4-hydroxysamic acid
    [3378] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxy-quinolin-4-yl) propyl] -1- [2- (3,4,5- Trifluorophenoxy) -ethyl] piperidine-4-hydroxysamic acid
    [3379] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxy-quinolin-4-yl) propyl] -1- [3- (2,4,6- Trifluorophenyl) prop-2-ynyl] piperidine-4-hydroxysamic acid
    [3380] 4- [3- (R, S) -Fluoro-3- (3-morpholinomethyl-6-methoxy-quinolin-4-yl) propyl] -1- [3- (3,4,5- Trifluorophenyl) prop-2-ynyl] piperidine-4-hydroxysamic acid
    [3381] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2-fluorophenyl) allyl] piperidine-4-carboxylic acid
    [3382] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3-fluorophenyl) allyl] piperidine-4-carboxylic acid
    [3383] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (4-fluorophenyl) allyl] piperidine-4-carboxylic acid
    [3384] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3-difluorophenyl) allyl] piperidine-4-carboxylic acid
    [3385] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4-difluorophenyl) allyl] piperidine-4-carboxylic acid
    [3386] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,6-difluorophenyl) allyl] piperidine-4-carboxylic acid
    [3387] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5-difluorophenyl) allyl] piperidine-4-carboxylic acid
    [3388] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4-difluorophenyl) allyl] piperidine-4-carboxylic acid
    [3389] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,5-trifluorophenyl) allyl] piperidine-4-carboxylic acid
    [3390] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,4-trifluorophenyl) allyl] piperidine-4-carboxylic acid
    [3391] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,3,6-trifluorophenyl) allyl] piperidine-4-carboxylic acid
    [3392] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,5-trifluorophenyl) allyl] piperidine-4-carboxylic acid
    [3393] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,4,6-trifluorophenyl) allyl] piperidine-4-carboxylic acid
    [3394] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,4,5-trifluorophenyl) allyl] piperidine-4-carboxylic acid
    [3395] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (3,5,6-trifluorophenyl) allyl] piperidine-4-carboxylic acid
    [3396] The present invention will be described in more detail by the following examples, which are not intended to limit the invention.
    [3397] Example 1
    [3398] 4- [3- (3-Chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] -piperidine-4-carboxylic acid dihydrochloride
    [3399] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] -piperidine in 7.72 cm 3 of aqueous 6N hydrochloric acid A mixture of 0.6 g of -4-carboxylate is heated for 2 hours with stirring under an inert atmosphere at a temperature of 100 ° C. After cooling to about 20 ° C, the reaction mixture was concentrated under reduced pressure (5 kPa) at a temperature of 40 ° C. The residue obtained is immersed in a 10 cm 3 dichloromethane / methanol mixture (90/10 on a volume basis). The mixture was concentrated to dryness under the above conditions. 0.58 g of 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] -piperidine-4-carboxylic acid di Hydrochloride is obtained in the form of a beige foam that melts (decomposes) at 130 ° C.
    [3400] 1 H NMR spectrum (250 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)) at a temperature of 373K: 1.50 to 2.30 (mts: total 8H); 2.70 to 3.80 (mts: total 10H); 3.99 (s: 3 H); 7.09 (dd, J = 5 and 3.5 Hz: 1H); 7.29 (broad d, J = 3.5Hz: 1H); 7.40 (d, J = 2.5 Hz: 1H); 7.46 (dd, J = 9 and 2.5 Hz: 1H); 7.64 (broad d, J = 5 Hz: 1H); 7.99 (d, J = 9 Hz: 1H); 8.67 (s: 1 H).
    [3401] Benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] -piperidine-4-carboxylate
    [3402] 0.6 g of 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate in acetonitrile of 20 cm 3 , 2- (2-bromoethylthio) A mixture of 0.36 g of thiophene and 0.22 g of potassium carbonate is heated for 16 hours with stirring under an inert atmosphere at a temperature of 80 ° C. After cooling to 20 ° C., the reaction mixture was concentrated to dryness under reduced pressure (5 kPa) at a temperature of 40 ° C. The residue obtained was chromatographically eluted with a mixture of dichloromethane / methanol (97.5 / 2.5 on a volume basis) in a column of silica gel (particle size 40-63 μ; diameter 3.5 cm; height 28 cm) under a nitrogen pressure of 100 kPa. Purification gave 35-cm 3 fractions. Fractions 15-20 were combined and then concentrated to dryness under the above conditions. 0.67 g benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] -piperidine-4-carboxyl The rate was obtained in the form of an orange viscous oil.
    [3403] Infrared spectrum (CCl 4 ) 2955; 1727; 1622; 1503; 1229; 1117; 833 and 698 cm -1 .
    [3404] Benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -piperidine-4-carboxylate
    [3405] Benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl]-in 50 cm 3 of dichloromethane with 1.27 cm 3 of trifluoroacetic acid stirred under an inert atmosphere at a temperature of 20 ° C. To a solution of 2.05 g of 1- (tert-butyloxycarbonyl) piperidine-4-carboxylate was added. After 30 minutes, an additional 1.27 cm 3 of trifluoroacetic acid was added, followed by an additional 30 minutes after 1.27 cm 3 . The reaction was achieved by the final addition of 1.27 cm 3 of trifluoroacetic acid. After 1 hour, the reaction mixture was concentrated under reduced pressure (5 kPa) at a temperature of 40 ° C. The evaporation residue is taken up in 50 cm 3 of ethyl acetate and 20 cm 3 of water. After 5 g of potassium carbonate was added and stirred for 5 minutes, the precipitate was allowed to separate and the separated organic phase was washed twice with 10 cm 3 of distilled water and then with 20 cm 3 of 10 wt% aqueous sodium chloride solution. After drying over magnesium sulfate and filtration, the organic solution was concentrated at a temperature of 40 ° C. under reduced pressure (5 kPa). The residue obtained was subjected to a mixture of dichloromethane / methanol / 32% aqueous ammonia (89/10/1 by volume) in a column of silica gel (particle size 40-63 μ; diameter 3.5 cm; height 30 cm) under a nitrogen pressure of 100 kPa. Purification by chromatography eluting with) gave 40-cm 3 fractions. Fractions 14-23 were combined and then concentrated to dryness under the above conditions. 1.36 g of benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate was obtained in the form of a beige solid that melts at 95 ° C.
    [3406] Infrared spectrum (KBr) 2960; 1721; 1621; 1503; 1232; 1115; 829 and 744 cm -1 .
    [3407] Benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- (tert-butyloxycarbonyl) -piperidine-4-carboxylate
    [3408] 1.98 g of benzyl 4-allyl-1- (tert-butyloxycarbonyl) piperidine-4-carboxylate was cooled to a temperature of -30 ° C and 9-borabicyclo in tetrahydrofuran [3.3.1 ] 11.32 cm 3 of 0.5 M solution of nonane was added under stirring under inert atmosphere. After addition, the temperature of the mixture was maintained at about 20 ° C. The resulting solution was stirred for an additional 4 hours before 40 cm 3 of dioxane, 0.183 g of diphenylphosphinoferrocenepalladium chloride, 2 g of 4-bromo-3-chloro-6-methoxyquinoline and 3.0 g of 3 Potassium phosphate was added. After stirring for 16 hours at a temperature of 60 ° C., the reaction mixture was cooled to about 20 ° C. and then filtered. The insoluble material was washed three times with 20 cm 3 of ethyl acetate and the filtrate and wash water combined and stirred with 40 cm 3 of water and 100 cm 3 of ethyl acetate. The organic phase was separated by sedimentation and washed twice with 20 cm 3 of water and then with 40 cm 3 of 10% by weight aqueous sodium chloride solution, dried over magnesium sulfate, filtered and concentrated at 40 ° C. under reduced pressure (5 kPa). . The obtained residue was chromatographed while eluting with a mixture of dichloromethane / methanol (98.5 / 1.5 by volume) in a column of silica gel (particle size 40-63 μ; diameter 3.5 cm; height 30 cm) under a nitrogen pressure of 100 kPa. Purification gave 35-cm 3 fractions. Fractions 22 to 29 were combined and then concentrated to dryness under the above conditions. 2.09 g of benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- (tert-butyloxycarbonyl) -piperidine-4-carboxylate dark yellow Obtained in the form of an oil.
    [3409] Infrared spectrum (CCl 4 ) 2930; 1728; 1695; 1622; 1503; 1230; 1172; 833 and 697 cm -1 .
    [3410] Benzyl 4-allyl-1- (tert-butyloxycarbonyl) piperidine-4-carboxylate
    [3411] 15.4 g of potassium carbonate followed by 10.6 cm 3 of benzyl bromide in a solution of 20 g of 4-allyl-1- (tert-butyloxycarbonyl) piperidine-4-carboxylic acid in 200 cm 3 of dimethylformamide Was added under stirring under an inert atmosphere. The mixture was stirred at a temperature of about 20 ° C. for 16 hours and then filtered. Insoluble matter was washed twice with 100 cm 3 of ethyl acetate. The filtrate was extracted once with ethyl acetate once and 150cm 3 of water and the wash water were combined for the following mixture was added to 250cm 3 of water to 500cm 3. The organic extracts were combined, washed with 125 cm 3 of 10% aqueous sodium chloride solution, dried over magnesium sulfate, filtered and concentrated under reduced pressure (5 kPa) at a temperature of 40 ° C. An oil was obtained, which was chromatographed while eluting with a mixture of dichloromethane / methanol (99/1 by volume) in a column of silica gel (particle size 40-63 μ; diameter 7 cm; height 30 cm) under a nitrogen pressure of 100 kPa. Purification was carried out to collect 200-cm 3 fractions. Fractions 6-16 were combined and then concentrated to dryness under reduced pressure (5 kPa) at a temperature of 40 ° C. 25 g of benzyl 4-allyl-1- (tert-butyloxycarbonyl) piperidine-4-carboxylate were obtained in the form of a pale yellow liquid.
    [3412] Infrared spectrum (CH 2 Cl 2 ): 2980; 1725; 1683; 1426; 1171; 1142; 974 and 924 cm -1 .
    [3413] 4-allyl-1- (tert-butyloxycarbonyl) piperidine-4-carboxylic acid
    [3414] 30.62 g of ethyl 4-allyl-1- (tert-butyloxycarbonyl) piperidine-4-carboxylate, pre-dissolved in 4.44 cm 3 of water and 150 cm 3 of tetrahydrofuran, was treated with 350 cm 3 of tetrahydro To a mixture of 48.52 g of potassium tert-butoxide in furan was added under stirring under inert atmosphere and cooled to a temperature of 0 ° C. After the temperature was reduced to 20 ° C., the mixture was stirred at this temperature for 24 hours. 300 cm 3 of ice cold water was added to the reaction mixture, and the mixture was then concentrated to dryness under reduced pressure at a temperature of 40 ° C. The aqueous residue was extracted with 300 cm 3 of diethyl ether. For 16 hours after which had been stagnant the addition of aqueous hydrochloric acid of about 215cm 3 and acidified to pH 3-4, and then the aqueous phase was extracted three times with diethyl ether of 300cm 3. The ether extracts were combined, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (5 kPa) at a temperature of 40 ° C. 26.1 g of 4-allyl-1- (tert-butyloxycarbonyl) piperidine-4-carboxylic acid were obtained in the form of a gray solid.
    [3415] Mass spectrum: EI m / z = 269 M +. m / z = 168 (M-C 5 H 9 O 2 ) +
    [3416] m / z = 124 (m / z = 168-CO 2 ) + m / z = 57 C 4 H 9 +
    [3417] Reference peak
    [3418] Ethyl allyl-1- (tert-butyloxycarbonyl) piperidine-4-carboxylate
    [3419] 70 cm 3 (2.5 M concentration) of a solution of butyllithium in hexane was added to 150 cm 3 of tetrahydrofuran cooled to a temperature of −70 ° C. while stirring under an inactivation atmosphere, followed by 50 cm 3 of tetrahydrofuran and tetrahydrofuran 300 cm. 3 diisopropylamine in 23cm 3 which had been dissolved in advance was added. After addition of 50 cm 3 of tetrahydrofuran, the mixture was stirred at about −70 ° C. for 15 minutes, and then ethyl 1- (tert-butyloxycarbonyl) iso dissolved in 400 cm 3 of tetrahydrofuran. 45.15 g of nifecotate was added and finally 50 cm 3 of the same solvent was added. After stirring for 1 hour the mixture at a temperature of -70 ℃ the allyl bromide was added to 16.7cm 3 which had been pre-dissolved in 150cm 3 of tetrahydrofuran and the mixture was warmed to about 20 ℃, and then the mixture was stirred for 17 hours. The mixture was poured into 200 cm 3 saturated aqueous ammonium chloride solution and then extracted with about 2 liters of ethyl acetate. The combined extracts were dried over sodium sulfate, then filtered and concentrated under reduced pressure (5 kPa) at a temperature of 40 ° C. Obtained an oil and purified by chromatography eluting with a mixture of dichloromethane / methanol (99.5 / 0.5 by volume) in a column of silica gel (diameter 12 cm; height 50 cm) under a nitrogen pressure of 100 kPa to obtain a 200-cm 3 fraction. Collected. Fractions 20 to 84 were combined and then concentrated under reduced pressure (5 kPa) at a temperature of 40 ° C. 27.85 g of ethyl 4-allyl-1- (tert-butyloxycarbonyl) piperidine-4-carboxylate were obtained in the form of a yellow oil.
    [3420] Mass spectrum: EI m / z = 297 M +. m / z = 240 (M-C 4 H 9 ) +
    [3421] m / z = 196 (m / z = 240-CO 2 ) + m / z = 168
    [3422] (m / z = 240-CO 2 Et) + m / z = 124
    [3423] (m / z = 168-CO 2 ) + m / z = 57 C 4 H 9 + reference peak
    [3424] Ethyl 1- (tert-butyloxycarbonyl) isonipate
    [3425] Under an inert atmosphere over a period of triethylamine 88.3cm 3 in an hour and then added with stirring to the Chapeco ethyl isobutyl you in a 1500cm 3 of dichloromethane cooled to a temperature of 5 ℃ 100g lactate solution, over the same time dichloro methane 300cm 3 166.6 g of di-tert-butyl dicarbonate dissolved in advance was added thereto. The reaction mixture was reduced to a temperature of 20 ° C. with stirring for 16 hours. After further adding 41.6 g of di-tert-butyl dicarbonate dissolved in 70 cm 3 of dichloromethane, the reaction mixture was stirred at about 20 ° C. for 3 hours and then washed twice with 600 cm 3 saturated aqueous sodium chloride solution, After drying over sodium sulfate, it was filtered and concentrated at a temperature of 40 ° C. under reduced pressure. 171 g of ethyl-1- (tert-butyloxycarbonyl) isonipecotate were obtained in the form of a brown oil.
    [3426] Mass spectrum: DCI m / z = 275 MNH 4 + reference peak m / z = 258 MH +
    [3427] 2- (2-bromoethylsulfanyl) thiophene is described in Sadykhov, KI, Aliev, SM and Seidov, MM Khim. Geterotsikl. Soedin, 3 , 344-5 (1975).
    [3428] 4-bromo-3-chloro-6-methoxyquinoline
    [3429] To a mixture of 20 g of 3-chloro-4-hydroxy-6-methoxyquinoline in acetonitrile 1000 cm 3 was added 80.8 g of triphenylphosphine bromide and stirred at a temperature of 85 ° C. for 2 hours 30 minutes. The resulting solution was cooled to 20 ° C. and then stirred at the same temperature for 16 hours. The reaction mixture is concentrated under reduced pressure (5 kPa) at a temperature of 40 ° C. and the evaporated residue is added to 200 cm 3 saturated aqueous sodium hydrogen carbonate solution and 200 cm 3 ethyl acetate. The organic phase was sedimented and separated and washed twice with 200 cm 3 of distilled water. The aqueous phase was extracted once more with ethyl acetate and then the organic extracts were combined, dried over magnesium sulfate, filtered and concentrated under reduced pressure at a temperature of 40 ° C. The product obtained was purified by chromatography eluting with a mixture of cyclohexane / ethyl acetate (70/30 on a volume basis) in a column of silica gel (7.5 cm in diameter; 700 g of silica mass) under a nitrogen pressure of 100 kPa. Fractions corresponding to the expected product were collected. These fractions were combined and concentrated under the same conditions as above. 20.7 g of 4-bromo-3-chloro-methoxyquinoline were obtained in the form of a white solid that melts at 108 ° C.
    [3430] Mass spectrum: EI m / z = 271 M +. Reference peak m / z = 256
    [3431] (M-CH 3 ) + m / z = 228 (m / z = 256-CO) +
    [3432] m / z = 149 (m / z = 228-Br) +
    [3433] m / z = 114 (m / z = 149-Cl) +.
    [3434] 3-chloro-4-hydroxy-6-methoxyquinoline
    [3435] 14.26 g of N-chlorosuccinimide was added to a mixture of 17 g of 4-hydroxy-6-methoxyquinoline in acetic acid 700 cm 3 with stirring at 20 ° C., and then the mixture was heated to a temperature of 50 to 70 ° C. for 4 hours. It was. The resulting solution was subsequently cooled to about 20 ° C. and then concentrated to dryness under reduced pressure (5 kPa) at a temperature of 40 ° C. The solid residue is taken up in 250 cm 3 saturated aqueous sodium hydrogen carbonate solution. The mixture was stirred for 1 hour. Insoluble material was filtered off and washed three times with 250 cm 3 of water. The obtained crystals were dried at a temperature of 20 ° C. under reduced pressure (10 Pa) for 3 hours. 20 g of 3-chloro-4-hydroxy-6-methoxyquinoline were obtained in the form of a yellow solid.
    [3436] Mass spectrum: EI m / z = 209 M +. Reference peak m / z = 194
    [3437] (M-CH 3 ) + m / z = 166 (m / z = 194-CO) + .
    [3438] 4-hydroxy-6-methoxyquinoline
    [3439] A suspension of 53.3 g of 4-hydroxy-6-methoxy-quinoline-3-carboxylic acid in 1000 cm 3 of diphenyl ether was heated for 2 hours and 45 minutes with stirring to a temperature of 250-260 ° C. The reaction mixture was cooled to about 20 ° C. After stirring for 16 hours at this temperature, the mixture was put into 1 liter of pentane with stirring and filtered. The cake obtained was washed three times with 100 cm 3 of pentane and three times with 100 cm 3 of diisopropyl ether. 37 g of 4-hydroxy-6-methoxyquinoline were obtained in the form of a beige solid after drying in the air.
    [3440] Mass spectrum: DCI m / z = 176 MH + reference peak
    [3441] 4-hydroxy-6-methoxyquinoline-3-carboxylic acid is described in BR Baker and Ray R. Bramhall, J. Med. Chem. 15 , 230 (1972).
    [3442] Example 2
    [3443] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) ethyl] piperidine-4-carboxylic acid
    [3444] Benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) ethyl] -pi in aqueous 5M hydrochloric acid 10cm 3 A mixture of 0.7 g of ferridine-4-carboxylate was stirred at a temperature of 100 ° C. for 5 hours. After cooling to about 20 ° C, the reaction mixture was concentrated to dryness under reduced pressure (5 kPa) at a temperature of 40 ° C. The obtained residue was eluted with dichloromethane / methanol / 28% aqueous ammonia (89/10/1 by volume) in a column of silica gel (particle size 40-63 μ; diameter 2.5 cm; height 35 cm) under a nitrogen pressure of 100 kPa. Purification was carried out by chromatography to collect 25-cm 3 fractions. These fractions were combined and concentrated under the above conditions. The evaporated residue obtained was slurried in 10 cm 3 of diisopropyl ether. The resulting crystalline product was filtered off, washed twice with the same solvent of 5 cm 3 and then air dried. 0.37 g of 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) ethyl] -piperidine-4 The carboxylic acid was obtained in the form of a white solid which melts at 204 ° C.
    [3445] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.20 to 2.15 (mt: 10H); 2,62 (t, J = 5.5 Hz: 2H); 2.65 to 2.80 (mt: 2H); 3.18 (mt: 2 H); 3.96 (s: 3 H); 4.08 (t, J = 5.5 Hz: 2H); 6.60 to 6.85 (mt: 3H); 7.38 (d, J = 2.5 Hz: 1 H); 7.46 (dd, J = 9 and 2.5 Hz: 1H); 7.97 (d, J = 9 Hz: 1 H); 8.68 (s: 1 H).
    [3446] Benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) ethyl] piperidine-4-carboxylate
    [3447] 1.36 g benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -piperidine-4-carboxylate in acetonitrile 45 cm 3 , 0.95 g 1- (2-bromine A suspension of moethoxy) -3,5-difluorobenzene (90% purity) and 0.5 g of potassium carbonate was heated with stirring at a temperature of 80 ° C. for 16 hours under an inert atmosphere. After cooling to 20 ° C., the reaction mixture was filtered and the insoluble material was washed with acetonitrile. The filtrate and wash water were combined and concentrated under reduced pressure (5 kPa) at a temperature of 40 ° C. The evaporated residue was purified by chromatography, eluting with dichloromethane / methanol (97/3 by volume) in a column of silica gel (particle size 40-63 μ; diameter 3.5 cm; height 45 cm) under a nitrogen pressure of 100 kPa. cm 3 fractions were collected. Fractions 18-23 were collected. These fractions were combined and concentrated to dryness at a temperature of 40 ° C. under reduced pressure (5 kPa). 1.56 g Benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) ethyl] -piperidine- 4-carboxylate was obtained in the form of an orange oil.
    [3448] Infrared spectrum (CH 2 Cl 2 ): 2955; 1723; 1622; 1599; 1229; 1153; 1116 and 843 cm -1 .
    [3449] Benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate was prepared in Example 1.
    [3450] Example 3
    [3451] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- (2-cyclohexylethyl) piperidine-4-carboxylic acid
    [3452] Benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylethyl] -piperidine-4-carboxylate in 9.6 cm 3 of aqueous 5M hydrochloric acid 0.6 g of the mixture was heated with stirring for 5 h at a temperature of 100 ° C. The resulting solution was concentrated under reduced pressure (5 kPa) at a temperature of 40 ° C. The resulting evaporation residue was slurried in diisopropyl ether. The resulting crystalline product was filtered, washed with the same solvent and oven-dried to a temperature of 60 ° C. under reduced pressure (10 Pa.) A solid was obtained which was subjected to a column of silica gel (particle size 40-63 μm; diameter under 100 kPa nitrogen pressure). 25-cm 3 fractions were collected by chromatography, eluting with dichloromethane / methanol / 32% aqueous ammonia (89/10/1 by volume) at 2.5 cm; height 40 cm). Concentrated at a temperature of 40 ° C. A crystalline product was obtained, 5cm 3 of di-isopropyl ether and the mixture was stirred at the. After washing with the same solvent and the resulting product filtered off and dried atmosphere of 0.33g 4- [3- (3- chloro-6-methoxy-quinolin-4-yl ) Propyl] -1- [2- (cyclohexylethyl) piperidine-4-carboxylic acid was obtained in the form of a white solid that melts at 234 ° C.
    [3453] 1 H NMR spectra (300 MHz, CD 3 OD-d 4 , δ (ppm)): 0.95 to 2.20-2.42-2.90 to 3.15 and 3.30 to 3.50 (mt, broad d, J = 13.5 Hz, mt and mt respectively) : Total 29H); 4.11 (s: 3 H); 7.52 (mt: 2 H); 8.02 (broad d, J = 9 Hz: 1H); 8.68 (s: 1 H).
    [3454] Benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- (2-cyclohexylethyl) piperidine-4-carboxylate
    [3455] To a solution of 1.36 g of benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -piperidine-4-carboxylate in acetonitrile 50 cm 3 in 0.56 cm 3 2-cyclo Hexylethyl bromide and 0.5 g of potassium carbonate were added at 20 ° C. under stirring under inert atmosphere. The resulting suspension was heated to about 80 ° C. for 16 hours, cooled to a temperature of 20 ° C., and then the reaction mixture was filtered and concentrated to dryness under reduced pressure (5 kPa) at a temperature of 40 ° C. The residue obtained was purified by chromatography, eluting with dichloromethane / methanol (97/3 by volume) in a column of silica gel (particle size 40-63 μ; diameter 3.5 cm; height 45 cm) under a nitrogen pressure of 100 kPa to 40 -cm 3 fractions were collected. Fractions 22 to 30 were combined and concentrated to dryness at a temperature of 40 ° C. under reduced pressure (5 kPa). 1.33 g of benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclohexylethyl] -piperidine-4-carboxylate Obtained in form.
    [3456] Infrared spectrum (CCl 4 ): 2925; 1727; 1622; 1503; 1230; 1116; 833 and 697 cm -1 .
    [3457] Benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] piperidine-4-carboxylate was prepared in Example 1.
    [3458] Example 4
    [3459] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl) piperidine-4-carboxylic acid dihydrochloride
    [3460] 5M hydrochloric 8cm 3 of benzyl 4- [3- (3-chloro-6-methoxy-quinolin-4-yl) propyl] -1- (3-phenylpropyl) piperidine-4-carboxylate 0.5g of 100 ℃ It was heated for 5 hours while stirring to a temperature of. After cooling to about 20 ° C., the reaction mixture was concentrated at 40 ° C. under reduced pressure (5 kPa). The evaporated residue obtained was placed in 6 cm 3 of a mixture of dichloromethane / methanol (90/10 on a volume basis), and the mixture was concentrated to dryness again under the above conditions. A foam was obtained, which was slurried in 5 cm 3 of diisopropyl ether. The resulting crystalline product was filtered and washed three times with the same solvent of 5 cm 3 and then dried in an oven under reduced pressure (10 Pa) at a temperature of 50 ° C. 0.46 g of 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl) piperidine-4-carboxylic acid dihydrochloride in the form of a beige solid Obtained.
    [3461] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.40 to 2.25 and 2.50 to 3.60 (mts: 20H total); 3.96 (s: 3 H); 7.10 to 7.45 (mt: 5H); 7.39 (d, J = 2.5 Hz: 1 H); 7.47 (dd, J = 9 and 2.5 Hz: 1H); 7.98 (d, J = 9 Hz: 1 H); 8.70 (s: 1 H);
    [3462] Benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl) piperidine-4-carboxylate
    [3463] 1.36 g benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -piperidine-4-carboxylate, 0.55 cm 3 1-bromo- in acetonitrile 45 cm 3 A solution of 3-phenylpropane and 0.5 g of potassium carbonate was heated at 80 ° C. with stirring under inert atmosphere for 16 hours. After cooling, the reaction mixture was filtered and the insoluble material was washed with acetonitrile. The filtrate was concentrated to dryness under reduced pressure (5 kPa) at a temperature of 40 ° C. An oil was obtained, which was purified by chromatography eluting with dichloromethane / methanol (97/3 by volume) in a column of silica gel (particle size 40-63 μ; diameter 3.5 cm; height 30 cm) under a nitrogen pressure of 100 kPa. 40-cm 3 fractions were collected. Fractions 21-25 were combined and concentrated as above. 21 g of benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [3-phenylpropyl) -piperidine-4-carboxylate in the form of an orange viscous oil Obtained.
    [3464] Infrared spectrum (CH 2 Cl 2 ): 2948; 2812; 1722; 1622; 1504; 1229; 1118; 1029 and 834 cm -1 .
    [3465] Benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate was prepared in Example 1.
    [3466] Example 5
    [3467] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl] piperidine-4-carboxylic acid trihydrochloride
    [3468] Ethyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thio-ethyl] piperidine in aqueous 5M hydrochloric acid 7cm 3 A mixture of 0.4 g of -4-carboxylate was maintained for 4 hours with stirring under an inert atmosphere at a temperature of 100 ° C. After cooling to about 20 ° C., the reaction mixture was concentrated at 40 ° C. under reduced pressure (5 kPa). The obtained residue was put in 10 cm 3 of a mixture of dichloromethane / methanol (90/10 by volume), and the mixture was concentrated to dryness under the above conditions. 0.45 g of 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyrid-2-yl) thioethyl] -piperidine-4-carboxylic acid Trihydrochloride was obtained in the form of a foam that melts (decomposes) at 132 ° C.
    [3469] ' H NMR Spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.59 (mt: 2H); 1.65 to 1.95 (mt: 4H); 2.20 (broad d, J = 13.5 Hz: 2H); 2.86 (mt: 2 H); 3.10 to 3.65 (mt: 8H); 3.99 (s: 3 H); 7.19 (broad dd, J = 7,5 and 4.5 Hz: 1H); 7.35 to 7.50 (mt: 2H); 7.50 (dd, J = 9 and 3 Hz: 1H); 7.71 (isolated t, J = 7,5 and 1.5 Hz: 1H); 8.01 (d, J = 9 Hz: 1H); 8.48 (broad d, J = 4.5 Hz: 1H); 8.74 (s: 1 H); 10.70 (multiple lines: 1H).
    [3470] Ethyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2-pyrid-2-yl) thioethyl] piperidine-4-carboxylate
    [3471] Ethyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2-pyrid-2-yl) thioethyl] piperidine-4-carboxylate Is a method analogous to that described in Example 1 using ethyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -piperidine-4-carboxylate hydrochloride as starting material It was prepared by.
    [3472] Infrared spectrum (CCl 4 ): 2955; 1726; 1622; 1580; 1503; 1414; 1229; 1125; 1030 and 833 cm -1 .
    [3473] Ethyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -piperidine-4-carboxylate hydrochloride
    [3474] Ethyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- (tert-butyloxycarbonyl) -piperidine-4-carboxylate in dioxane 40 cm 3 2.6 To the mixture was added 14 cm 3 of 4N hydrochloric dioxane and stirred for 16 hours at a temperature of 20 ° C. To the obtained suspension was diluted by addition of 100 cm 3 of diethyl ether, stirred at about 20 ° C. for 1 hour and then filtered. The cake was washed twice with 40 cm 3 of diethyl ether and then dried in a drier under reduced pressure (5 kPa). 1.9 g of ethyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -piperidine-4-carboxylate were obtained in the form of a white solid.
    [3475] Infrared spectrum (KBr): 2965; 2474; 1720; 1620; 1584; 1416; 1241; 1119; 1019; 872 and 743 cm -1 .
    [3476] Ethyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- ( Level 3 -Butyloxycarbonyl) piperidine-4-carboxylate
    [3477] 30 cm 3 of 0.5M solution of 9-borabicyclo- [3.3.1] nonane in tetrahydrofuran was converted to ethyl 4-allyl-1- (tert-butyloxycarbonyl-piperidine-) in 30 cm 3 of tetrahydrofuran. 2.96 g of 4-carboxylate was added to the solution and stirred at a temperature of −10 ° C. under an inert atmosphere while maintaining a temperature below 0 ° C. After addition, the temperature of the mixture was adjusted to about 20 ° C. and the mixture further Stir for 4 hours 3.1 g of 4-bromo-3-chloro-6-methoxyquinoline were added, followed by 50 cm 3 of dioxane, 6.4 g of trivalent potassium phosphate and 0.22 g of diphenylphosphino Ferrocene palladium chloride was added The reaction mixture was heated to a temperature of 50 ° C. for 16 hours After cooling to a temperature of 20 ° C., the mixture was filtered and the cake washed three times with 50 cm 3 of ethyl acetate. Wash with 100 cm 3 of water and then with 50 cm 3 of saturated aqueous sodium chloride solution. Wash twice. The organic phase is dried over magnesium sulfate, filtered and concentrated under reduced pressure (5 kPa) at a temperature of 40 ° C. A brown oil is obtained which is a column of silica gel (particle size 20−) under a nitrogen pressure of 50 kPa. Purification by chromatography eluting with cyclohexane / ethyl acetate (80/20 on a volume basis) at 45 μ; diameter 4.5 cm; height 42 cm .. Fractions containing the expected product were collected. Concentrated at reduced pressure (5 kPa) 2.62 g of ethyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- (tert-butyloxycarbonyl) Piperidine-4-carboxylate was obtained in the form of a yellow oil.
    [3478] Infrared spectrum: (CH 2 Cl 2 ): 1720; 1682; 1622; 1504; 1423; 1367; 1229; 1174; 1027 and 834 cm -1 .
    [3479] Ethyl 4-allyl-1- (tert-butyloxycarbonyl) -piperidine-4-carboxylate was prepared in Example 1
    [3480] Example 6
    [3481] Sodium salt of 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1-heptylpiperidine-4-carboxylic acid
    [3482] A mixture of 0.48 g of benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1-heptylpiperidine-4-carboxylate in 7 cm 3 aq. It was stirred for 6 hours at a temperature of ℃. After cooling to about 20 ° C., the reaction mixture was stirred for 24 hours and then evaporated under reduced pressure (5 kPa) at a temperature of 40 ° C. The obtained residue was chromatographed while eluting with dichloromethane / methanol / aqueous ammonia (84/15/1 by volume) in a column of silica gel (particle size 40-60 μ; diameter 2.5 cm; height 35 cm) under a nitrogen pressure of 100 kPa. Purification by chromatography gave 40-cm 3 fractions. Fractions 19 to 24 were combined and concentrated as above. The solid obtained was stirred in 10 cm 3 of diisopropyl ether, filtered and washed three times with 5 cm 3 of diisopropyl ether. 0.35 g of 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1-heptylpiperidine-4-carboxylic acid was obtained in the form of a solid melting at 223 ° C.
    [3483] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , (Ppm)): 0.87 (t, J = 7 Hz: 3H); 1.10-1.45 (mt: 12H); 1.45 to 1.70 (mt: 4H); 1.85 to 2.05 (mt: 2H); 1.97 (broad d, J = 10.5 Hz: 2H); 2.17 (broad t, J = 7.5 Hz: 2H); 2.45 to 2.60 (mt: 2H); 3.15 (mt: 2 H); 3.97 (s: 3 H); 7.40 (mt: 1 H); 7.44 (dd, J = 9 and 3 Hz: 1H); 7.95 (d, J = 9 Hz: 1H); 8.66 (s: 1 H).
    [3484] Benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1-heptylpiperidine-4-carboxylate
    [3485] Acetonitrile 45cm 3 of 1.36g of iodine in a solution of heptane also 0.61cm 3 1- benzyl-4- [3- (3-chloro-6-methoxy-quinolin-4-yl) propyl] piperidine-4-carboxylate The rate and 0.5 g of potassium carbonate were added with stirring under an inert atmosphere at a temperature of 20 ° C. After heating to 80 ° C. for 18 hours, additional 1.17 cm 3 of 1-iodoheptane was added. After 40 hours of heating to 80 ° C., the reaction mixture was cooled to 20 ° C., filtered and concentrated under reduced pressure (1 kPa) at a temperature of 50 ° C. The obtained residue was purified by chromatography, eluting with a mixture of dichloromethane / methanol (95/5 by volume) in a column of silica gel (particle size 40-60 μ; diameter 3.5 cm; height 35 cm) under a nitrogen pressure of 100 kPa. 35-cm 3 fractions were collected. Fractions 18 to 26 were combined and concentrated as above. 0.36 g of benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1-heptylpiperidine-4-carboxylate was obtained.
    [3486] Infrared spectrum (CH 2 Cl 2 ): 2957; 2931; 1722; 1622; 1504; 1229; 1159; 1118;
    [3487] Benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate was prepared as described in Example 1.
    [3488] Example 7
    [3489] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine-4-carboxylic acid dihydrochloride
    [3490] Ethyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) -ethyl] piperidine-4-carboxyl in aqueous 6M hydrochloric acid 8cm 3 The mixture of rate 0.55 g was heated for 5 hours with stirring at a temperature of 100 ° C. under an inert atmosphere. After stirring at 20 ° C. for 18 hours, the resulting solution was concentrated at 40 ° C. under reduced pressure (5 kPa). The evaporated residue obtained was placed in 10 cm 3 of a mixture of dichloromethane / methanol (90/10 by volume) and the mixture was concentrated under the above conditions. 0.59 g of 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2-cyclopentylthio) ethyl] piperidine-4-carboxylic acid dihydrochloride at 129 ° C Obtained in the form of a soft foam which melted at.
    [3491] ' H NMR Spectrum: (300 MHz, (CD 3 ) 2 SO-d 6 , (Ppm)): 1.30 to 2.10 (mt: 14H); 2.15 (broad d, J = 13.5 Hz: 2H); 2.65 to 3.00 (mt: 4H); 3.05 to 3.40 (mt: 5H); 3.46 (broad d, J = 12 Hz: 2H); 3.97 (s: 3 H); 7.42 (d, J = 2.5 Hz: 1H); 7.48 (dd, J = 9 and 2.5 Hz: 1H); 7.99 (d, J = 9 Hz: 1H); 8.72 (s: 1 H); 10.55 to 10.90 (multiple lines: 1H).
    [3492] Ethyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine-4-carboxylate
    [3493] To a solution of 0.607 g of (2-chloroethylthio) cyclopentane in 50 cm 3 of acetonitrile at a temperature of 20 ° C., 1.2 g of ethyl 4- [3- (3-chloro-6-methoxyquinoline- under stirring under an inert atmosphere 4-yl) propyl] piperidine-4-carboxylate, 0.51 g potassium carbonate and 0.61 g potassium iodide were added. After heating for 20 hours to a temperature of 80 ° C, the reaction mixture was cooled to a temperature of about 20 ° C, filtered and then concentrated under reduced pressure (5 kPa) at a temperature of 50 ° C. The obtained residue was purified by chromatography eluting with a mixture of 35-cm 3 in a column of silica gel (particle size 40-60 μ; diameter 3.5 cm) under a nitrogen pressure of 100 kPa. Fractions 25 to 31 were combined and concentrated as above. 0.9 g of ethyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine-4-carboxylate was obtained. .
    [3494] Infrared spectrum (CCl 4 ): 958; 1726; 1622; 1503; 1229; 1117; 1030 and 833 cm -1 .
    [3495] Ethyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate was prepared as described in Example 5.
    [3496] Example 8
    [3497] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thien-2-yl) thioethyl] piperidine-4-acetic acid
    [3498] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2-thien-2-yl) thioethyl] pi was carried out in a similar manner to the above example. Ferridine-4-acetic acid was prepared.
    [3499] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , (Ppm)): 1.30 to 1.70 (mt: 8H); 2.14 (s: 2 H); 2.33 (mt: 4 H); 2.45 to 2.60 (mt: 2H); 2.92 (broad t, J = 7Hz: 2H); 3.13 (mt: 2 H); 3.96 (s: 3 H); 7.05 (dd, J = 5.5 and 3.5 Hz: 1H); 7.18 (dd, J = 3.5 and 1 Hz: 1H); 7.39 (d, J = 3 Hz: 1 H); 7.44 (dd, J = 9 and 3 Hz: 1H); 7.60 (dd, J = 5.5 and 1 Hz: 1H); 7.95 (d, J = 9 Hz: 1H); 8.66 (s: 1 H).
    [3500] Example 9
    [3501] {4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidin-4-yl} methanol
    [3502] {4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthio) ethyl] piperidine-4 was carried out in a similar manner to the above example. -Yl} methanol was prepared.
    [3503] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , (Ppm)): 1.15 to 1.75 (mt: 14H); 1.95 (mt: 2 H); 2.20 to 2.40 (mt: 4H); 2.44 (mt: 2 H); 2.57 (mt: 2 H); 3.05 to 3.25 (mt: 5H); 3.97 (s: 3 H); 4.38 (t, J = 5.5 Hz: 1H); 7.38 (d, J = 3 Hz: 1H); 7.45 (dd, J = 9 and 3 Hz: 1H); 7.96 (d, J = 9 Hz: 1H); 8.68 (s: 1 H).
    [3504] Example 10
    [3505] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1-[(3-phenylpropyl) piperidin-4-yl] methanol
    [3506] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1-[(3-phenylpropyl) piperidin-4-yl] methanol in a manner similar to that of the above example Was prepared.
    [3507] ' H NMR Spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , (Ppm)): 1.59 (mt: 2H); 1.65 to 1.95 (mt: 4H); 2.20 (broad d, J = 13.5 Hz: 2H); 2.86 (mt: 2 H); 3.10 to 3.65 (mt: 8H); 3.99 (s: 3 H); 7.19 (broad dd, J = 7.5 and 4.5 Hz: 1H); 7.35 to 7.50 (mt: 2H); 7.50 (dd, J = 9 and 3 Hz: 1H); 7.71 (isolated t, J = 7.5 and 1.5 Hz: 1H); 8.01 (d, J = 9 Hz: 1H); 8.48 (broad d, J = 4.5 Hz: 1H); 8.74 (s: 1 H); 10.70 (multiple lines: 1H).
    [3508] Example 11
    [3509] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] piperidine-4-carboxylic acid
    [3510] Ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl in aqueous 5N hydrochloric acid 5cm 3 and dioxane 3cm 3 ] A mixture of 0.4 g of piperidine-4-carboxylate was maintained for 20 hours when stirred at a temperature of 100 ° C. under an inert atmosphere. After cooling to about 20 ° C., the reaction mixture was concentrated to dryness at a temperature of 40 ° C. under reduced pressure (2 kPa). The mixture was purified by chromatography eluting with a column of silica gel (particle size 40-63 μ; diameter 1.5 cm; mass 55 g) under atmospheric pressure with chloroform / methanol / aqueous ammonia (12/3 / 0.5 by volume). cm 3 fractions were collected. Fractions 5-12 were combined and concentrated to dryness under the above conditions. 0.26 g of 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] piperidine-4-carboxylic acid Obtained as a solid of white crystalline solid, melting at 180 ° C.
    [3511] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.31 (very broad t), J = 13 Hz: 2H); 1.50 to 1.70 (mt: 4H); 1.85 to 2.05 (mt: 4H); 2.45 (broad t, J = 7Hz: 2H); 2.60 (broad d, J = 11 Hz: 2H); 2.91 (broad t, J = 7Hz: 2H); 3.04 (very broad t, J = 6 Hz: 2H); 3.96 (s: 3 H); 7.04 (dd, J = 5 and 3.5 Hz: 1H); 7.17 (dd, J = 3.5 and 1 Hz: 1H); 7.35 (d, J = 2.5 Hz: 1H); 7.40 (dd, J = 9 and 2.5 Hz: 1H); 7.60 (dd, J = 5 and 1 Hz: 1H); 7.97 (d, J = 9 Hz: 1 H); 8.70 (broad s: 1H).
    [3512] Ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] piperidine-4-carboxylate
    [3513] 0.8 g of ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate in acetonitrile 10 cm 3 , 2- (2-bromoethylthio) A mixture of 0.6 g of thiophene and 1.5 g of potassium carbonate was heated to a temperature of 80 ° C. for 18 hours with stirring under an inert atmosphere. After cooling to 20 ° C., the reaction mixture was concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. The obtained residue is taken up in dichloromethane and water. The organic phase was washed with water and saturated sodium chloride solution, dried over magnesium sulfate, filtered and concentrated to dryness under the above conditions. The residue was purified by chromatography eluting with a column of silica gel (particle size 70-200 μ; diameter 3 cm; mass 50 g) under atmospheric pressure with ethyl acetate / petroleum ether (40-65 ° C.) (75/25 by volume). 30-cm 3 fractions were collected. Fractions 3-5 were combined and concentrated to dryness under the above conditions. 0.7 g of ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] piperidine-4-carboxyl The rate was obtained in the form of a dark colorless oil.
    [3514] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 0.99 (t, J = 7 Hz: 3H); 1.34 (very broad t, J = 12 Hz: 2H); 1.45 to 1.65 (mt: 4H); 1.85 to 2.00 (mt: 4H); 2.44 (broad t, J = 7Hz: 2H); 2.59 (broad d, J = 11.5 Hz: 2H); 2.89 (broad t, J = 7Hz: 2H); 3.03 (very broad t, J = 6.5 Hz: 2H); 3.94 (s: 3 H); 3.96 (q, J = 7 Hz: 2H); 7.02 (dd, J = 5 and 3.5 Hz: 1H); 7.16 (dd, J = 3.5 and 1 Hz: 1H); 7.32 (d, J = 2.5 Hz: 1H); 7.39 (dd, J = 9 and 2.5 Hz: 1H); 7.58 (dd, J = 5 and 1 Hz: 1H); 7.96 (d, J = 9 Hz: 1H); 8.69 (broad s: 1H).
    [3515] Ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate
    [3516] Ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl]-in dichloromethane 10 cm 3 , with stirring, 2 cm 3 of trifluoroacetic acid at a temperature of 5 ° C. under inert atmosphere. To a solution of 0.5 g of 1- (tert-butyloxycarbonyl) piperidine-4-carboxylate was added. After 45 minutes, the reaction mixture was concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. The residue was taken up in diethyl ether and washed sequentially with saturated potassium bicarbonate solution and saturated potassium carbonate solution. The organic phase was washed with 5 cm 3 of water and then with saturated sodium chloride solution, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. 0.26 g of ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate was obtained in the form of a thick oil.
    [3517] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.02 (t, J = 7 Hz: 3H); 1.28 (mt: 2 H); 1.45 to 1.70 (mt: 4H); 1.90 (broad d, J = 13.5 Hz: 2H); 2.46 (broad t, J = 12 Hz: 2H); 2.79 (d mt, J = 12 Hz: 2H); 3.06 (broad t, J = 6Hz: 2H); 3.95 (s: 3 H); 3.98 (q, J = 7 Hz: 2H); 7.35 (d, J = 2.5 Hz: 1H); 7.40 (dd, J = 9 and 2.5 Hz: 1H); 7.97 (d, J = 9 Hz: 1 H); 8.70 (d, J = 1 Hz: 1H).
    [3518] Ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- (tert-butyloxycarbonyl) piperidine-4-carboxylate
    [3519] 1.4 g of ethyl 4-allyl-1- (tert-butyloxycarbonyl) piperidine-4-carboxylate was cooled to a temperature of -30 [deg.] C., followed by 9-borabicyclo in tetrahydrofuran [ 3.3.1] 11 cm 3 of 0.5 M solution of nonane was added under stirring under inert atmosphere. After addition, the temperature of the mixture was reduced to about 20 ° C. The resulting solution was stirred for a further 4 hours, followed by 0.09 g of palladium diphenylphosphinoferrocene chloride, 1.4 g of 4-iodo-3-fluoro-6-methoxyquinoline and 2.5 g of trivalent potassium phosphate. Added. After stirring for 16 hours at a temperature of 60 ° C., the reaction mixture was cooled to about 20 ° C. and then concentrated to dryness at a temperature of 40 ° C. under reduced pressure (2 kPa). The obtained residue was taken in ethyl acetate and water, and the phases were separated by sedimentation, and then the organic phase was dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. The residue obtained was purified by chromatography, eluting with a mixture of dichloromethane / ethyl acetate (98/2 by volume) in a column of silica gel (particle size 70-200 μ; diameter 4.5 cm; mass 125 g) under atmospheric pressure. -cm 3 fractions were collected. Fractions 98-170 were combined and concentrated to dryness under the above conditions. Dark brown oil with 1.5 g of ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- (tert-butyloxycarbonyl) piperidine-4-carboxylate Obtained in the form of.
    [3520] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.02 (t, J = 7 Hz: 3H); 1.30 (mt: 2 H); 1.39 (s: 9 H); 1.45 to 1.70 (mt: 4H); 1.92 (broad d, J = 13.5 Hz: 2H); 2.81 (mt: 2 H); 3.05 (broad t, J = 6.5 Hz: 2H); 3.69 (broad d, J = 13.5 Hz: 2H); 3.95 (s: 3 H); 4.00 (q, J = 7 Hz: 2H); 7.34 (d, J = 2.5 Hz: 1 H); 7.40 (dd, J = 9 and 2.5 Hz: 1H); 7.97 (d, J = 9 Hz: 1 H); 8.70 (d, J = 1 Hz: 1H).
    [3521] 4-iodo-3-fluoro-6-methoxyquinoline
    [3522] Tetrahydrofuran 80cm 3 of diisopropylamine 1.8cm 3 the temperature of the cooled and hexanes-butyllithium 1.6M solution in 7.7cm 3 of -75 ℃ was added with stirring under an inert atmosphere. After stirring for 20 minutes at a temperature of -75 ° C, a solution of 2.2 g of 3-fluoro-6-methoxyquinoline in 20 cm 3 of tetrahydrofuran was added. The resulting solution was stirred for a further 4 h, after which a solution of 3.3 g of double-sublimed iodine in 10 cm 3 of tetrahydrofuran was added. After stirring for 2 hours at a temperature of 20 ° C., the reaction mixture was hydrolyzed with 200 cm 3 of 90/10 tetrahydrofuran / water mixture followed by 100 cm 3 saturated sodium chloride solution and 150 cm 3 ethyl acetate. The mixture was washed three times with 80 cm 3 saturated sodium chloride solution, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure at a temperature of 40 ° C. The residue obtained was purified by chromatography, eluting with a mixture of 90/10 petroleum ether / ethyl acetate on a column of silica gel (particle size 70-200 μ; diameter 5 cm; height 35 cm) under atmospheric pressure. Fractions 66-95 were combined and concentrated to dryness under reduced pressure (5 kPa) at a temperature of 40 ° C. 0.9 g of 4-iodo-3-fluoro-6-methoxyquinoline was obtained in the form of a cream solid.
    [3523] ' H NMR Spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 4.00 (s: 3H); 7.31 (d, J = 2.5 Hz: 1H); 7.47 (dd, J = 9 and 2.5 Hz: 1H); 8.01 (d, J = 9 Hz: 1H); 8.64 (s: 1 H).
    [3524] 3-fluoro-6-methoxyquinoline
    [3525] A mixture of 23cm 3 methanol solution of 4-chloro-3-fluoro-6-methoxyquinoline 1.35g, triethylamine 1.1cm 3, 100mg of palladium on charcoal at a temperature of 20 ℃ under a hydrogen pressure of 2bar was stirred for 18 hours . The reaction mixture was filtered and then concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. The residue obtained was purified by chromatography, eluting with a mixture of dichloromethane / ethyl acetate (95/5 by volume) in a column of silica gel (particle size 70-200 μ; diameter 3 cm; mass 40 g) under atmospheric pressure. Fractions containing product were combined and concentrated to dryness according to the above conditions. 1 g of 3-fluoro-6-methoxyquinoline was obtained.
    [3526] ' H NMR Spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 3.92 (s: 3H); 7.40 (mt: 2 H); 8.07 (d, J = 9 Hz: 1H); 8.04 (dd, J = 10 and 3 Hz: 1H); 8.77 (d, J = 3 Hz: 1H).
    [3527] 4-chloro-3-fluoro-6-methoxyquinoline
    [3528] Tetrahydrofuran 50cm 3 of diisopropylamine 1.3cm 3 the temperature of the cooled and hexanes-butyllithium 1.6M solution in 5.8cm 3 of -75 ℃ was added with stirring under an inert atmosphere. After stirring for 20 minutes at a temperature of -75 ° C, a solution of 1.2 g of 4-chloro-6-methoxyquinoline in 20 cm 3 of tetrahydrofuran was added. The resulting solution was stirred for a further 4 hours, then a solution of 2.9 g of N-fluorobenzene sulfonimide in 10 cm 3 of tetrahydrofuran was added. After stirring for 2 hours at a temperature of 20 ° C., the reaction mixture was hydrolyzed with 200 cm 3 of 90/10 tetrahydrofuran / water mixture followed by 100 cm 3 saturated sodium chloride solution and 150 cm 3 ethyl acetate. The mixture was washed three times with 80 cm 3 saturated sodium chloride solution, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. The residue obtained was purified by chromatography, eluting with dichloromethane on a column of silica gel (particle size 70-200 μ; diameter 4 cm; mass 100 g) under atmospheric pressure. Fractions containing product were combined and concentrated to dryness under reduced pressure (5 kPa) at a temperature of 40 ° C. 0.4 g of 4-chloro-3-fluoro-6-methoxyquinoline were obtained.
    [3529] ' H NMR Spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 4.01 (s: 3H); 7.43 (d, J = 2.5 Hz: 1H); 7.52 (dd, J = 9 and 2.5 Hz: 1H); 8.07 (d, J = 9 Hz: 1H); 8.91 (d, J = 1 Hz: 1 H).
    [3530] 4-chloro-6-methoxyquinoline
    [3531] A mixture of 12 g of 4-hydroxy-6-methoxyquinoline in 50 cm 3 of oxychloride was stirred under an inert atmosphere for 2 hours. After cooling to about 20 ° C., the reaction mixture is concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C., then hydrolyzed with ice and brought to pH 10 with 5N sodium hydroxide solution. The mixture was extracted with ethyl acetate, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. The residue obtained was purified by chromatography, eluting with a mixture of dichloromethane / methanol (85/15 on a volume basis) in a column of silica gel (particle size 70-200 μ) under atmospheric pressure. Fractions containing product were combined and concentrated to dryness according to the above conditions. 12 g of 4-chloro-6-methoxyquinoline were obtained in the form of a white solid that melts at 82 ° C.
    [3532] ' H NMR Spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 3.958 (s: 3H); 7.45 (d, J = 2.5 Hz: 1H); 7.53 (dd, J = 9 and 2.5 Hz: 1H); 7.76 (d, J = 4.5 Hz: 1H); 8.04 (d, J = 9 Hz: 1H); 8.70 (d, J = 4.5 Hz: 1H).
    [3533] Ethyl-4-allyl-1- (tert-butyloxycarbonyl) -piperidine-4-carboxylate was prepared in Example 1.
    [3534] 4-hydroxy-6-methoxyquinoline was prepared as described in Example 1.
    [3535] Example 12
    [3536] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluoro-6-phenoxy) ethyl] piperidine-4 Carboxylic acid
    [3537] Ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluoro- in aqueous 5N hydrochloric acid 6 cm 3 and dioxane 10 cm 3 A mixture of 0.4 g of 6-phenoxy) ethyl] piperidine-4-carboxylate was maintained for 20 hours upon stirring at a temperature of 100 ° C. under an inert atmosphere. After cooling to about 20 ° C., the reaction mixture was concentrated to dryness at a temperature of 40 ° C. under reduced pressure (2 kPa). The obtained residue was purified by chromatography, eluting with chloroform / methanol / aqueous ammonia (12/3 / 0.5 by volume) in a column of silica gel (particle size 70-200 μ; diameter 1.5 cm; mass 50 g) under atmospheric pressure 15-cm 3 fractions were collected. Fractions 10-15 were combined and concentrated to dryness under the above conditions. 0.2 g 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluoro-6-phenoxy) ethyl] piperi Dean-4-carboxylic acid was obtained as a white solid, melting at 175 ° C.
    [3538] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.33 (very broad t, J = 13 Hz: 2H); 1.50 to 1.70 (mt: 4H); 1.95 (broad d, J = 13 Hz: 2H); 2.05 (broad t, J = 11.5 Hz: 2H); 2.60 (t, J = 6 Hz: 2H); 2.69 (broad d, J = 11.5 Hz: 2H); 3.04 (mt: 2 H); 3.96 (s: 3 H); 4.06 (t, J = 6 Hz: 2H); 6.65 to 6.85 (mt: 3H); 7.34 (d, J = 2.5 Hz: 1 H); 7.39 (dd, J = 9 and 2.5 Hz: 1H); 7.96 (d, J = 9 Hz: 1H); 8.69 (broad s: 1H).
    [3539] Ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluoro-6-phenoxy) ethyl] piperidine- 4-carboxylate
    [3540] 0.4 g of ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate in acetonitrile 10 cm 3 , 1- (2-bromoethoxy)- A mixture of 0.3 g of 3,5-difluorobenzene, 0.18 g of potassium iodide and 0.74 g of potassium carbonate was heated to a temperature of 75 ° C. for 18 hours with stirring under an inert atmosphere. After cooling to a temperature of 20 ° C, the reaction mixture was concentrated to dryness under reduced pressure (5 kPa) at a temperature of 40 ° C. The obtained residue is taken up in ethyl acetate and water. The organic phase was washed with water and saturated sodium chloride solution, dried over magnesium sulfate, filtered and concentrated to dryness under the above conditions. The residue was purified by chromatography eluting with dichloromethane on a column of silica gel (particle size 70-200 μ; diameter 1.5 cm; mass 35 g) under atmospheric pressure. Fractions 7-11 were combined and concentrated to dryness under the above conditions. 0.4 g of ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluoro-6-phenoxy) ethyl] pi Ferridine-4-carboxylate was obtained in the form of a dark colorless oil.
    [3541] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.00 (t, J = 7 Hz: 3H); 1.38 (very broad t, J = 12 Hz: 2H); 1.45 to 1.70 (mt: 4H); 1.90 to 2.10 (mt: 4H); 2.60 (t, J = 6 Hz: 2H); 2.69 (very broad d, J = 12 Hz: 2H); 3.05 (very broad t, J = 6.5 Hz: 2H); 3.95 (s: 3 H); 3.98 (q, J = 7 Hz: 2H); 4.06 (t, J = 6 Hz: 2H); 6.65 to 6.85 (mt: 3H); 7.34 (d, J = 2.5 Hz: 1 H); 7.40 (dd, J = 9 and 2.5 Hz: 1H); 7.97 (d, J = 9 Hz: 1 H); 8.70 (broad s: 1H).
    [3542] Ethyl 4-allyl-1- (tert-butyloxycarbonyl) -piperidine-4-carboxylate was prepared in Example 1.
    [3543] 1- (2-bromoethoxy) -3,5-difluorobenzene was obtained by applying the method described in Example 16.
    [3544] Example 13
    [3545] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro-6-phenoxy) ethyl] piperidine- 4-carboxylic acid dihydrochloride
    [3546] Benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro-6-phenoxy in aqueous 5N hydrochloric acid 50 cm 3 A mixture of 1 g of ethyl] piperidine-4-carboxylate was maintained for 20 hours when stirred at a temperature of 100 ° C. After cooling to about 20 ° C., the reaction mixture was concentrated to dryness at a temperature of 40 ° C. under reduced pressure (2 kPa). The obtained residue was taken in 50 cm 3 of acetone, filtered, washed three times with 15 cm 3 and then dried in a drier under reduced pressure (0.1 kPa) at a temperature of 40 ° C. 0.88 g of 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro-6-phenoxy) ethyl] pi Ferridine-4-carboxylic acid dihydrochloride was obtained in the form of a white solid that melts at 170 ° C.
    [3547] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.45 to 2.30 (mt: 8H); 2.85 to 3.70 (mt: 8H); 3.97 (s: 3 H); 4.50 (mt: 2 H); 7.15 (mt: 2 H); 7.40 (d, J = 3 Hz: 1H); 7.46 (dd, J = 9 and 3 Hz: 1H); 7.97 (d, J = 9 Hz: 1 H); 8.69 (s: 1 H); 10.07 (unisolated peak: 1H); 12.50 to 13.10 (broad unseparated peak: 1H).
    [3548] Benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro-6-phenoxy) ethyl] piperidine -4-carboxylate
    [3549] 1.4 g benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate hydrochloride in acetonitrile 100 cm 3 , 1- (2-bromoethoxy) A mixture of 0.9 g of -2,3,5-trifluorobenzene, 0.6 g of potassium iodide and 2 g of potassium carbonate was heated to a temperature of 75 ° C. for 18 hours with stirring under an inert atmosphere. After cooling to 20 ° C., the reaction mixture was filtered and washed three times with 30 cm 3 of acetonitrile. The filtrate was concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. The obtained residue was purified by chromatography eluting with ethyl acetate on a column of silica gel (particle size 20-45 μ; diameter 3 cm; height 27 cm) under atmospheric pressure to collect 50-cm 3 fractions. Fractions 9 to 23 were combined and concentrated to dryness under the above conditions. 1.27 g of benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluoro-6-phenoxy) ethyl] Piperidine-4-carboxylate was obtained in the form of a dark yellow oil.
    [3550] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.30 to 1.60 (mt: 4H); 1.72 (mt: 2 H); 1.95 to 2.15 (mt: 4H); 2.64 (t, J = 5.5 Hz: 2H); 2.71 (d-non isolated peak, J = 12 Hz: 2H); 3.13 (broad t, J = 7.5 Hz: 2H); 3.93 (s: 3 H); 4.16 (t, J = 5.5 Hz: 2H); 5.04 (s: 2 H); 6.95 to 7.15 (mt: 2H); 7.20 to 7.30 (mt: 5H); 7.34 (d, J = 3 Hz: 1 H); 7.45 (dd, J = 9 and 3 Hz: 1H); 7.97 (d, J = 9 Hz: 1 H); 8.67 (s: 1 H).
    [3551] Benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -piperidine-4-carboxylate hydrochloride
    [3552] A mixture of 17.4 g of benzyl 1-3-butyloxycarbonyl-4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate in 75 cm 3 of 5N hydrochloric acid Was dissolved in 200 cm 3 of dioxane and stirred at a temperature of 20 ° C. for 20 hours. 200 cm 3 of diethyl ether was added to the reaction mixture. The precipitate formed was filtered to yield benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate hydrochloride.
    [3553] ' H NMR Spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.49 (mt: 2H); 1.65 to 1.85 (mt: 4H); 2.11 (d-non-separated peak, J = 14 Hz: 2H); 2.78 (mt: 2 H); 3.10 to 3.25 (mt: 2H); 3.20 (broad t, J = 7.5 Hz: 2H); 3.96 (s: 3 H); 5.09 (s: 2 H); 7.28 (mt: 5 H); 7.43 (d, J = 3 Hz: 1H); 7.53 (dd, J = 9 and 3 Hz: 1 H); 8.06 (d, J = 9 Hz: 1H); 8.80 (s: 1 H); 9.05 to 9.30 (unseparated peak: 2H).
    [3554] 1- (2-bromoethoxy) -2,3,5-trifluorobenzene
    [3555] Of acetonitrile for 18 hours at a temperature of 75 ℃ with stirring under a 200cm 3 2,3,5- trifluoro phenol 11.4g, 1,2- dibromoethane 40.5cm an inert atmosphere for three and a mixture of potassium carbonate and 15.3g of Heated. After cooling to 20 ° C., the reaction mixture was filtered and washed four times with 50 cm 3 of acetonitrile. The filtrate was concentrated to dryness at a temperature of 40 ° C. under reduced pressure (2 kPa). The obtained residue was put in 150 cm 3 of petroleum ether (40-65 ° C.), filtered and washed three times with 30 cm 3 of petroleum ether (40-65 ° C.). The filtrate was concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. The obtained residue was purified by chromatography eluting with petroleum ether (40-65 ° C.) in a column of silica gel (particle size 20-45 μm; diameter 5 cm; height 33 cm) under atmospheric pressure to collect 100-cm 3 fractions. Fractions 28 to 63 were combined and concentrated to dryness under the above conditions. 16.15 g of 1- (2-bromoethoxy) -2,3,5-trifluorobenzene were obtained in the form of a dark colorless oil.
    [3556] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 3.83 (broad t, J = 5.5 Hz: 2H); 4.45 (broad t, J = 5.5 Hz: 2H); 7.00 to 7.15 (mt: 2H).
    [3557] Benzyl 4-allyl-1- (tert-butyloxycarbonyl) -piperidine-4-carboxylate was prepared in Example 1.
    [3558] Example 14
    [3559] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,5-difluoro-6-phenylthio) ethyl] piperidine-4- Carboxylic acid
    [3560] Benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl-1- [2- (2,5-difluoro-6- in 15 cm 3 of 5N hydrochloric acid aqueous solution and 15 cm 3 of dioxane A mixture of 1.3 g of piperidine-4-carbosylate was kept under an inert atmosphere for 20 hours with stirring at 100 ° C. After cooling to about 20 ° C., the reaction mixture was evaporated under reduced pressure (2 kPa) at 40 ° C. The residue obtained was dissolved four times with toluene and evaporated between each wash The oil obtained was dissolved in a chloroform / methanol / aqueous ammonia mixture (based on a 12/3 / 0.5 volume) and precipitated for phase separation. The organic phase was crystallized by washing with water and left for 20 hours The obtained solid was filtered off and placed in a drier and dried under reduced pressure (0.1 kPa) at a temperature of 40 ° C. 4- [3- (3-chloro-6- Methoxyquinolin-4-yl) propyl] -1- [2- (2,5-difluoro-6-phenylthio) ethyl] -piperidine-4-carboxylic acid 0.6 g was obtained in the form of a white crystalline solid which melts at 205 ° C.
    [3561] 1 H NMR spectrum (400 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.39 (unseparated peak: 2H); 1.55 (mt: 2 H); 1.70 (mt: 2 H); 1.90 to 2.20 (mt: 4H); 2.40 to 2.85 (broad unseparated peak: 4H); 3.05 to 3.25 (mt: 2H); 3.17 (broad t, J = 7.5 Hz: 2H); 3.96 (s: 3 H); 7.07 (mt: 1 H); 7.26 (mt: 1 H); 7.33 (mt: 1 H); 7.38 (d, J = 2.5 Hz: 1 H); 7.46 (dd, J = 9 and 2.5 Hz: 1H); 7.97 (d, J = 9 Hz: 1 H); 8.68 (s: 1 H); 12.00 to 12.50 (unseparated peak: 1H).
    [3562] Benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,5-difluoro-6-phenylthio) ethyl] piperidine-4 Carboxylate
    [3563] 1.4 g of benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate in 100 cm 3 of acetonitrile, 1- (2-bromoethylthio)- A mixture of 0.9 g of 2,5-difluorobenzene, 0.6 g of potassium iodide and 2 g of potassium carbonate was heated for 18 hours at 75 ° C. under inert atmosphere with stirring. After cooling to 20 ° C., the reaction mixture was concentrated to dryness at 40 ° C. under reduced pressure (2 kPa). The obtained residue was dissolved in water and extracted with ethyl acetate. The organic phase was washed with saturated sodium chloride solution, dried over magnesium sulfate and concentrated to dryness as described above. The obtained residue was purified by chromatography under atmospheric pressure on a silica gel column (particle size 70 to 200 µ; diameter 2.5 cm; mass 50 g) eluted with a mixture of ethyl acetate and dichloromethane (05/95 volume ratio) and collected in 15 cm 3 fractions. Fractions 21 to 100 were combined and then concentrated to dryness according to the above conditions. Benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,5-difluoro-6-phenylthio) ethyl] piperidine-4 1.35 g of carboxylate were obtained in the form of a white solid (melting point 95 ° C.).
    [3564] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.30 to 1.60 (mt: 4H); 1.71 (mt: 2 H); 1.85 to 2.05 (mt: 4H); 2.40 to 2.60 (mt: 2H); 2.66 (d-unseparated peaks, J = 12 Hz: 2H); 3.05 to 3.20 (mt: 2H); 3.11 (broad t, J = 7.5 Hz: 2H); 3.92 (s: 3 H); 5.03 (s: 2 H); 7.04 (mt: 1 H); 7.15 to 7.35 (mt: 7H); 7.35 (d, J = 3 Hz: 1H); 7.44 (dd, J = 9 and 3 Hz: 1H); 7.95 (d, J = 9 Hz: 1H); 8.66 (s: 1 H).
    [3565] 1- (2-bromoethylthio) -2,5-difluorobenzene
    [3566] A mixture of 5.8 g of S- (2,5) -difluorophenyl-dimethyl thiocarbamate in 80 cm 3 of a 10% solution of potassium hydroxide in methanol was heated under inert atmosphere at 100 ° C. for 1 hour. After cooling to 20 ° C., the reaction mixture was concentrated to dryness at 40 ° C. under reduced pressure (2 kPa). The obtained residue was dissolved in water, extracted with diethyl ether and acidified with 40 cm 3 of 5N hydrochloric acid. The aqueous phase was extracted twice with 30 cm 3 of diethyl ether. The organic phases were combined, washed with saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated to dryness as described above. The obtained residue was dissolved in 30 cm 3 of 1,2-dibromoethane and 0.5 g of aliquat 336, followed by addition of 20 cm 3 of a low temperature sodium hydroxide solution. The resulting solution was stirred for an additional 18 h at 20 ° C. and then washed twice with 15 cm 3 of water. The combined organic phases were washed with saturated sodium chloride solution, dried over sodium sulfate, filtered and concentrated to dryness as described above. The obtained residue was purified by chromatography under atmospheric pressure on a silica gel column (particle size 70 to 200 mu; diameter 2.5 cm; mass 75 g) eluted with petroleum ether and collected in 50 cm 3 fractions. Fractions 4 to 13 were combined and then concentrated to dryness according to the above conditions. 4.4 g of 1- (2-bromoethylthio) -2,5-difluorobenzene were obtained in the form of a colorless fluid oil.
    [3567] ' H NMR Spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 3.50 (mt: 2H); 3.66 (mt: 2 H); 7.15 (mt: 1 H); 7.32 (heterogeneous triplet, J = 9 and 4.5 Hz: 1H); 7.42 (ddd, J = 9-6.5 and 3 Hz: 1H).
    [3568] Dimethyl S- (2,5) -difluorophenylthiocarbamate
    [3569] 2 g of dimethyl O- (2,5) -difluorophenylthiocarbamate were heated at 235 ° C. for 40 minutes. The obtained residue was eluted with a mixture of petroleum ether and dichloromethane (50/50 volume ratio) and purified by chromatography on a silica gel column (particle size 70 to 200 mu; diameter 3 cm; mass 25 g), collected in 15 cm 3 fractions. Fractions 6-11 were combined and then concentrated to dryness under reduced pressure (2 kPa) at 40 ° C. 1.25 g of dimethyl S- (2,5) -difluorophenylthiocarbamate were obtained in the form of a white solid (melting point 96 ° C.).
    [3570] ' H NMR Spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 2.96 (unseparated peak: 3H); 3.08 (unisolated peak: 3H); 7.35 to 7.50 (mt: 3H).
    [3571] Dimethyl O- (2,5) -difluorophenylthiocarbamate
    [3572] 14.1 g of dimethylthiocarbamate chloride and 13 g of 1,4-diaza [2.2.2] tricyclooctane were added to the solution of 7.5 g of 2,5-difluorophenol in 120 cm 3 of dimethylformamide under stirring. After stirring at 20 ° C. for 1 hour, the reaction mixture was dissolved in 1dm 3 of water and 100 cm 3 of anhydrous hydrochloric acid and extracted with 400 cm 3 of diethyl ether. The organic phase was dried over sodium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa) at 40 ° C. temperature. The obtained residue was purified by chromatography under atmospheric pressure on a silica gel column (particle size 70 to 200 mu; diameter 10 cm; mass 400 g) eluted with a mixture of petroleum ether and dichloromethane (50/50 volume ratio). Fractions containing the expected product were combined and then concentrated to dryness at 40 ° C. under reduced pressure (5 kPa). 12.4 g of dimethyl O- (2,5) -difluorophenylthiocarbamate were obtained in solid form (melting point 62 ° C.).
    [3573] ' H NMR Spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 3.35 (s: 3H); 3.40 (s: 3 H); 7.15 to 7.30 (mt: 2H); 7.42 (heterogeneous triplet, J = 9.5 and 5.5 Hz: 1H).
    [3574] Benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate hydrochloride was prepared in Example 13.
    [3575] Example 15
    [3576] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,6-difluorophenoxy) ethyl] piperidine-4-carboxylic acid dihydro Chloride
    [3577] Benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,6-difluorophenoxy) -ethyl] pi in 50 cm 3 of 5N hydrochloric acid aqueous solution A mixture of 1 g of ferridine-4-carboxylate was maintained at 100 ° C. for 20 hours under inert atmosphere with stirring. After cooling to about 20 ° C., the reaction mixture was concentrated to dryness at 40 ° C. under reduced pressure (2 kPa). The obtained residue was dissolved in 50 cm 3 of acetone and stirred at 20 ° C. for 1 hour. The mixture was filtered, washed three times with 15 cm 3 of acetone, then placed in a dryer and dried under reduced pressure (0.1 kPa) at 40 ° C. 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,6-difluorophenoxy) ethyl] piperidine-4-carboxylic acid dihydro 0.86 g chloride was obtained in the form of a white solid (melting point 218 ° C.).
    [3578] ' H NMR Spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.59 (mt: 2H); 1.75 (mt: 2 H); 1.82 (very broad t, J = 14 Hz: 2H); 2.22 (broad d, J = 14 Hz: 2H); 2.98 (mt: 2 H); 3.22 (broad t, J = 7.5 Hz: 2H); 3.45 to 3.70 (mt: 4H); 3.98 (s: 3 H); 4.51 (t, J = 5 Hz: 2H); 7.15 to 7.25 (mt: 3H); 7.42 (d, J = 3 Hz: 1H); 7.48 (dd, J = 9 and 3 Hz: 1 H); 7.99 (d, J = 9 Hz: 1H); 8.72 (s: 1 H); 10.66 (unisolated peak: 1H).
    [3579] Benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,6-difluorophenoxy) ethyl] piperidine-4-carboxylate
    [3580] 1.4 g of benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate in 100 cm 3 of acetonitrile, 1- (2-bromoethoxy) -2 A mixture of 0.82 g of, 6-difluorobenzene, 0.6 g of potassium iodide and 2 g of potassium carbonate was heated for 18 hours at 75 ° C. under inert atmosphere with stirring. After cooling to 20 ° C., the reaction mixture was filtered and washed three times with 30 cm 3 of acetonitrile. The filtrate was concentrated to dryness at 40 ° C. under reduced pressure (2 kPa). The obtained residue was purified by chromatography under an atmospheric pressure on a silica gel column (particle size 20 to 45 µ; diameter 3 cm; height 27 cm) eluted with ethyl acetate and collected in 50 cm 3 fractions. Fractions 7 to 17 were combined and then concentrated to dryness according to the above conditions. Benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,6-difluorophenoxy) ethyl] piperidine-4-carboxylate 1.65 g was obtained in the form of a thick yellow oil.
    [3581] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.25 to 1.55 (mt: 4H); 1.70 (mt: 2 H); 1.90 to 2.10 (mt: 4H); 2.59 (t, J = 6 Hz: 2H); 2.66 (d-unseparated peaks, J = 12 Hz: 2H); 3.13 (broad t, J = 7.5 Hz: 2H); 3.93 (s: 3 H); 4.14 (t, J = 6 Hz: 2H); 5.03 (s: 2 H); 7.05 to 7.20 (mt: 3H); 7.35 (mt: 5 H); 7.35 (d, J = 3 Hz: 1H); 7.46 (dd, J = 9 and 3 Hz: 1H); 7.97 (d, J = 9 Hz: 1 H); 8.67 (s: 1 H).
    [3582] 1- (2-bromoethoxy) -2,6-difluorobenzene
    [3583] A mixture of 10 g of 2,6-difluorophenol, 40.5 cm 3 of 1,2-dibromoethane, and 15.3 g of potassium carbonate in 300 cm 3 of acetonitrile were heated for 18 hours at 75 ° C. under inert atmosphere with stirring. After cooling to 20 ° C., the reaction mixture was filtered and washed three times with 30 cm 3 of acetonitrile. The filtrate was concentrated to dryness at 40 ° C. under reduced pressure (2 kPa). The obtained residue was dissolved in 200 cm 3 of petroleum ether (40 to 65 ° C.), filtered and washed three times with 30 cm 3 of petroleum ether (40 to 65 ° C.). The filtrate was concentrated to dryness at 40 ° C. under reduced pressure (2 kPa). The obtained residue was purified by chromatography under atmospheric pressure on a silica gel column (particle size 20 to 45 mu; diameter 7 cm; height 28 cm) eluted with petroleum ether (40 to 65 ° C.) and collected in 100 cm 3 fractions. Fractions 22 to 58 were combined and then concentrated to dryness according to the above conditions. 14.5 g of 1- (2-bromoethoxy) -2,6-difluorobenzene was obtained in the form of a thick colorless oil.
    [3584] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 3.76 (broad t, J = 6 Hz: 2H); 4.42 (broad t, J = 6Hz: 2H); 7.10 to 7.25 (mt: 3H).
    [3585] Benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate hydrochloride was prepared in Example 13.
    [3586] Example 16
    [3587] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,5-difluorophenoxy) ethyl] piperidine-4-carboxylic acid dihydro Chloride
    [3588] Benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,5-difluorophenoxy) -ethyl] piperi in 50 cm 3 5N hydrochloric acid A mixture of 1 g of din-4-carboxylate was kept at 100 ° C. for 20 hours under inert atmosphere with stirring. After cooling to about 20 ° C., the reaction mixture was concentrated to dryness at 40 ° C. under reduced pressure (2 kPa). The obtained residue was dissolved in 50 cm 3 of acetone and stirred at 20 ° C. for 1 hour. The mixture was filtered, washed three times with 15 cm 3 of acetone, then placed in a dryer and dried under reduced pressure (0.1 kPa) at 40 ° C. 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,5-difluorophenoxy) ethyl] piperidine-4-carboxylic acid dihydro 0.8 g of chloride was obtained in the form of a white solid (melting point 180 ° C.).
    [3589] ' H NMR Spectrum (400 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.58 (mt: 2H); 1.72 (mt: 2 H); 1.84 (very broad t, J = 14 Hz: 2H); 2.19 (broad d, J = 14 Hz: 2H); 2.95 (mt: 2 H); 3.22 (broad t, J = 7.5 Hz: 2H); 3.53 (mt: 4 H); 3.98 (s: 3 H); 4.52 (t, J = 5 Hz: 2H); 6.84 (mt: 1 H); 7.22 (ddd, J = 9-7 and 3 Hz: 1H); 7.30 (ddd, J = 10.5-9 and 4.5 Hz: 1H); 7.42 (d, J = 2.5 Hz: 1H); 7.49 (dd, J = 9 and 2.5 Hz: 1H); 8.00 (d, J = 9 Hz: 1H); 8.74 (s: 1 H); 10.97 (unisolated peak: 1H).
    [3590] Benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,5-difluorophenoxy) ethyl] piperidine-4-carboxylate
    [3591] 1.4 g of benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate in 100 cm 3 of acetonitrile, 1- (2-bromoethoxy) -2 A mixture of 0.82 g, 5-difluorobenzene, 0.6 g potassium iodide and 2 g potassium carbonate was heated for 18 hours at 75 ° C. under inert atmosphere with stirring. After cooling to 20 ° C., the reaction mixture was filtered and washed three times with 30 cm 3 of acetonitrile. The filtrate was concentrated to dryness at 40 ° C. under reduced pressure (2 kPa). The obtained residue was purified by chromatography under an atmospheric pressure on a silica gel column eluting with ethyl acetate and collecting 30 cm 3 fractions (particle size 20 to 45 µ; diameter 2.4 cm; height 26 cm). Fractions 7-14 were combined and then concentrated to dryness according to the conditions. Benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,5-difluorophenoxy) ethyl] piperidine-4-carboxylate 1.6 g was obtained in the form of a thick yellow oil.
    [3592] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.35 to 1.60 (mt: 4H); 1.73 (mt: 2 H); 1.95 to 2.15 (mt: 4H); 2.63 (t, J = 5.5 Hz: 2H); 2.72 (d-non-separated peak, J = 12 Hz: 2H); 3.14 (broad t, J = 7.5 Hz: 2H); 3.92 (s: 3 H); 4.12 (t, J = 5.5 Hz: 2H); 5.04 (s: 2 H); 6.75 (three triplets, J = 9 and 3 Hz: 1H); 7.13 (ddd, J = 10.5-7.5 and 3 Hz: 1H); 7.20 to 7.30 (mt: 6H); 7.34 (d, J = 3 Hz: 1 H); 7.45 (dd, J = 9 and 3 Hz: 1H); 7.97 (d, J = 9 Hz: 1 H); 8.67 (s: 1 H).
    [3593] 1- (2-bromoethoxy) -2,5-difluorobenzene
    [3594] A mixture of 10 g of 2,5-difluorophenol, 40.5 cm 3 of 1,2-dibromoethane and 15.3 g of potassium carbonate in 200 cm 3 of acetonitrile was heated for 18 hours at 75 ° C. under inert atmosphere with stirring. After cooling to 20 ° C., the reaction mixture was filtered and washed four times with 50 cm 3 of acetonitrile. The filtrate was concentrated to dryness at 40 ° C. under reduced pressure (2 kPa). The obtained residue was dissolved in 150 cm 3 of petroleum ether (40 to 65 ° C.), filtered and washed three times with 30 cm 3 of petroleum ether (40 to 65 ° C.). The filtrate was concentrated to dryness at 40 ° C. under reduced pressure (2 kPa). The obtained residue was purified by chromatography under atmospheric pressure on a silica gel column (particle size 20 to 45 µ; diameter 7 cm; height 49 cm) eluted with petroleum ether (40 to 65 ° C.) and collected in 100 cm 3 fractions. Fractions 29 to 88 were combined and then concentrated to dryness according to the above conditions. 13.5 g of 1- (2-bromoethoxy) -2,5-difluorobenzene was obtained in the form of a colorless fluid oil.
    [3595] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 3.85 (broad t, J = 6 Hz: 2H); 4.44 (broad t, J = 6Hz: 2H); 6.82 (mt: 1 H); 7.18 (ddd, J = 9-7 and 3 Hz: 1H); 7.29 (ddd, J = 11-9 and 5 Hz: 1H).
    [3596] Benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate hydrochloride was prepared in Example 13.
    [3597] Example 17
    [3598] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3-difluorophenoxy) ethyl] piperidine-4-carboxylic acid dihydro Chloride
    [3599] Benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3-difluorophenoxy) -ethyl] pi in 50 cm 3 of 5N aqueous hydrochloric acid solution A mixture of 1 g of ferridine-4-carboxylate was maintained at 100 ° C. for 20 hours under inert atmosphere with stirring. After cooling to about 20 ° C., the reaction mixture was concentrated to dryness at 40 ° C. under reduced pressure (2 kPa). The obtained residue was dissolved in 50 cm 3 of acetone and stirred at 20 ° C. for 1 hour. The mixture was filtered, washed three times with 15 cm 3 of acetone, then placed in a dryer and dried under reduced pressure (0.1 kPa) at 40 ° C. 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3-difluorophenoxy) ethyl] piperidine-4-carboxylic acid dihydro 0.9 g of chloride was obtained in the form of a white solid (melting point 259 ° C.).
    [3600] 1 H NMR spectrum (400 MHz (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.45 to 1.65 (mt: 2H); 1.73 (mt: 2 H); 1.81 (very broad t, J = 14 Hz: 2H); 2.20 (broad d, J = 14 Hz: 2H); 2.97 (mt: 2 H); 3.22 (broad t, J = 7.5 Hz: 2H); 3.45 to 3.60 (mt: 4H); 3.98 (s: 3 H); 4.54 (t, J = 5 Hz: 2H); 7.09 (mt: 2 H); 7.20 (mt: 1 H); 7.42 (d, J = 2.5 Hz: 1H); 7.48 (dd, J = 9 and 2.5 Hz: 1H); 7.99 (d, J = 9 Hz: 1H); 8.72 (s: 1 H); 10.70 (unisolated peak: 1H); 12.40 to 13.30 (broad unseparated peak: 1H).
    [3601] Benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3-difluorophenoxy) ethyl] piperidine-4-carboxylate
    [3602] 1.4 g of benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate in 100 cm 3 of acetonitrile, 1- (2-bromoethoxy) -2 A mixture of 0.82 g of, 3-difluorobenzene, 0.6 g of potassium iodide and 2 g of potassium carbonate was heated for 18 h at 75 ° C. under inert atmosphere with stirring. After cooling to 20 ° C., the reaction mixture was filtered and washed three times with 30 cm 3 of acetonitrile. The filtrate was concentrated to dryness at 40 ° C. under reduced pressure (2 kPa). The obtained residue was purified by chromatography under atmospheric pressure on a silica gel column (particle size 20 to 45 µ; diameter 2.7 cm; height 32 cm) eluted with ethyl acetate and collected in 30 cm 3 fractions. Fractions 7 to 21 were combined and then concentrated to dryness according to the above conditions. Benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3-difluorophenoxy) ethyl] piperidine-4-carboxylate 1.6 g was obtained in the form of a thick yellow oil.
    [3603] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.35 to 1.55 (mt: 4H); 1.72 (mt: 2 H); 1.95 to 2.15 (mt: 4H); 2.64 (t, J = 6 Hz: 2H); 2.72 (d-non-separated peak, J = 12 Hz: 2H); 3.13 (broad t, J = 7.5 Hz: 2H); 3.93 (s: 3 H); 4.15 (t, J = 6 Hz: 2H); 5.04 (s: 2 H); 6.90 to 7.20 (mts: 3H); 7.25 (mt: 5 H); 7.35 (d, J = 3 Hz: 1H); 7.46 (dd, J = 9 and 3 Hz: 1H); 7.97 (d, J = 9 Hz: 1 H); 8.67 (s: 1 H).
    [3604] 1- (2-bromoethoxy) -2,3-difluorobenzene
    [3605] A mixture of 10 g of 2,3-difluorophenol, 40.5 cm 3 of 1,2-dibromoethane and 15.3 g of potassium carbonate in 200 cm 3 of acetonitrile was heated for 48 h at 75 ° C. under inert atmosphere with stirring. After cooling to 20 ° C., the reaction mixture was filtered and washed six times with 30 cm 3 of acetonitrile. The filtrate was concentrated to dryness at 40 ° C. under reduced pressure (2 kPa). The obtained residue was purified by chromatography under atmospheric pressure on a silica gel column (particle size 20 to 45 µ; diameter 7 cm; height 42 cm) eluted with a mixture of dichloromethane and ethyl acetate (90/10 volume ratio) and collected in 100 cm 3 fractions. Fractions 4 to 10 were combined and concentrated to dryness according to the above conditions. The obtained residue was purified by chromatography under atmospheric pressure on a silica gel column (particle size 20 to 45 µ; diameter 5 cm; height 30 cm) eluted with petroleum ether (40 to 65 ° C.) and collected in 100 cm 3 fractions. Fractions 34 to 82 were combined and then concentrated to dryness according to the above conditions. 13.6 g of 1- (2-bromoethoxy) -2,3-difluorobenzene were obtained in the form of a colorless fluid oil.
    [3606] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 3.85 (broad t, J = 6 Hz: 2H); 4.44 (broad t, J = 6Hz: 2H); 6.82 (mt: 1 H); 7.18 (ddd, J = 9-7 and 3 Hz: 1H); 7.29 (ddd, J = 11-9 and 5 Hz: 1H).
    [3607] Benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate hydrochloride was prepared in Example 13.
    [3608] Example 18
    [3609] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- (2- thiazole-2-thioethyl) piperidine-4-carboxylic acid
    [3610] Ethyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl-1- (2-thiazole-2-thioethyl) piperidine-4-carboxylate in 6 cm 3 of 5N hydrochloric acid aqueous solution 0.3 g of the mixture was kept at 100 ° C. for 6 hours under inert atmosphere with stirring. After cooling to 20 ° C. and stirring for 16 h, the reaction mixture was concentrated to dryness at 40 ° C. under reduced pressure (2 kPa). The obtained residue was dissolved in 10 cm 3 of dichloroethane containing 10% methanol, and then concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. The obtained residue was purified by chromatography under atmospheric pressure on a silica gel column (particle size 40 to 60 µ; diameter 2.5 cm; height 30 cm) eluted with a dichloroethane / methanol / aqueous ammonia mixture (89/10/1 volume ratio). Fractions 18 to 41 were combined and concentrated to dryness under these conditions. The obtained residue was dissolved in 5 cm 3 of isopropyl ether, filtered and then dried in a drier at 40 ° C. under reduced pressure (0.1 kPa). 0.24 g of 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- (2-thiazole-2-thioethyl) piperidine-4-carboxylic acid as a white solid Obtained (melting point 200 ° C.).
    [3611] ' H NMR Spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.34 (mt: 2H); 1.55 (mt: 2 H); 1.69 (mt: 2 H); 1.85 to 2.15 (mt: 4H); 2.59 (broad t, J = 7Hz: 2H); 2.67 (d-non-separated peak, J = 12 Hz: 2H); 3.17 (broad t, J = 6Hz: 2H); 3.20 to 3.50 (mt: 2H); 3.96 (s: 3 H); 7.38 (broad s: 1H); 7.45 (broad dd, J = 9 and 2.5 Hz: 1H); 7.63 (d, J = 3 Hz: 1 H); 7.71 (d, J = 3 Hz: 1H); 7.96 (d, J = 9 Hz: 1H); 8.68 (s: 1 H); 11.90 to 12.55 (very broad unseparated peak: 1H).
    [3612] Ethyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- (2-thiazole-2-thioethyl) piperidine-4-carboxylate
    [3613] 0.28 g of 2-mercaptothiazole, 0.33 g of potassium carbonate and 0.29 g of potassium iodide were added to ethyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- in 50 cm 3 of acetonitrile. To a solution of 0.9 g of (2-chloroethyl) piperidine-4-carboxylate was added at 20 ° C. under inert atmosphere while stirring. After heating to 80 ° C. for 20 hours, the reaction mixture was cooled to about 20 ° C., filtered and concentrated to dryness at 50 ° C. under reduced pressure (2 kPa). The obtained residue was purified by chromatography under a nitrogen pressure of 100 kPa on a silica gel column (particle size 40 to 60 µ; diameter 3.5 cm; height 35 cm) eluted with a dichloromethane / methanol mixture (95 / 0.5 volume ratio) and collected in 40 cm 3 fractions. It was. The fractions containing the product were combined and then eluted with an ethyl acetate / cyclohexane mixture (75/25 volume ratio) and collected in 30 cm 3 fractions under silica 100 kPa pressure on a silica gel column (particle size 40-60 μ; diameter 3.5 cm; height 30 cm). Purification by chromatography. Fractions 23-40 were combined and concentrated to dryness as described above. 0.75 g of ethyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- (2-thiazole-2-thioethyl) piperidine-4-carboxylate were obtained. .
    [3614] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.05 (t, J = 7 Hz: 3H); 1.38 (mt: 2 H); 1.52 (mt: 2 H); 1.68 (mt: 2 H); 1.90 to 2.05 (mt: 4H); 2.59 (t, J = 7 Hz: 2H); 2.68 (broad d, J = 12 Hz: 2H); 3.17 (broad t, J = 7.5 Hz: 2H); 3.25 to 3.40 (mt: 2H); 3.97 (s: 3 H); 4.00 (q, J = 7 Hz: 2H); 7.38 (d, J = 2.5 Hz: 1 H); 7.46 (dd, J = 9 and 2.5 Hz: 1H); 7.63 (d, J = 3.5 Hz: 1 H); 7.71 (d, J = 3.5 Hz: 1 H); 7.96 (d, J = 9 Hz: 1H); 8.68 (s: 1 H).
    [3615] Ethyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- (2-chloroethyl) piperidine-4-carboxylate
    [3616] 1.8 g of ethyl 4- [3- (3-chloro-6-methoxy-quinolin-4-yl) propyl] -1- (2-hydroxyethyl) piperidine-4-carboxylate in 40 cm 3 of dichloromethane To the solution 1.21 cm 3 of thionyl chloride was added at 20 ° C. under stirring. After stirring for 48 h at 20 ° C, the reaction mixture was concentrated under reduced pressure (1 kPa) at 50 ° C. The residue was dissolved in 50 cm 3 of water and 50 cm 3 of ethyl acetate with vigorous stirring at 20 ° C., and then 10 g of potassium carbonate was added. The organic phase was washed with 25 cm 3 of water and 25 cm 3 of saturated sodium chloride solution, dried over magnesium sulfate, filtered and concentrated at 50 ° C. under reduced pressure (1 kPa). 1.8 g of ethyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- (2-chloroethyl) piperidine-4-carboxylate were obtained.
    [3617] Infrared spectrum (CCl 4 ): 2957; 1726; 1622; 1503; 1230; 1116; 1029 and 833 cm -1
    [3618] Ethyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- (2-hydroxyethyl) piperidine-4-carboxylate
    [3619] Ethyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] piperidine at 20 ° C. under an inert atmosphere with stirring in a solution of 1.17 cm 3 2-iodoethanol in acetonitrile 80 cm 3 3.9 g of 4-carboxylate and 2.07 g of potassium carbonate were added. After heating at 80 ° C. for 23 hours, 1.17 cm 3 of 2-iodoethanol was further added. After heating at 80 ° C. for 40 hours, the reaction mixture was cooled to about 20 ° C., filtered and concentrated at 50 ° C. under reduced pressure (1 kPa). The obtained residue was eluted with a dichloromethane / methanol / aqueous ammonia mixture (89/10/1 volume ratio) and collected in 50 cm 3 fractions under a silica gel column (particle size 40 to 60 μ; diameter 4 cm; height 60 cm) under nitrogen pressure of 100 kPa. Purification by chromatography. Fractions 14-17 were combined and concentrated as described above. 1.9 g of ethyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- (2-hydroxyethyl) piperidine-4-carboxylate were obtained.
    [3620] Infrared spectrum (CCl 4 ): 2439; 2952; 1726; 1622; 1503; 1230; 1116; 1029 and 833 cm -1 .
    [3621] Example 19
    [3622] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (cyclopentylthioethyl) piperidine- 4-yl] -methanol dihydrochloride
    [3623] {4- [3- (3-chloro-6-methoxyquinolin-4-yl) -3- (R, S) -hydroxypropyl] piperidin-4-yl} methanol dihydro in 25 cm 3 of acetonitrile A mixture of 0.6 g chloride, 0.24 g 1-bromo-2- (cyclopentylthio) ethyl, 0.22 g potassium iodide and 0.9 g potassium carbonate was heated under stirring at 75 ° C. for 20 hours. After cooling to 20 ° C., the reaction mixture was concentrated to dryness at 40 ° C. under reduced pressure (2 kPa). The obtained residue was dissolved in 20 cm 3 of water and then extracted three times with 20 cm 3 of ethyl acetate. The combined organic phases were dried over magnesium sulfate, filtered and concentrated to dryness as described above. The residue obtained was purified by chromatography under a 50 kPa nitrogen pressure on a silica gel column (particle size 20-45 μ; diameter 3 cm; height 18 cm) eluting with a dichloromethane / methanol mixture (90/10 volume ratio). Fractions containing the expected product were combined and concentrated to dryness under the conditions described above. The obtained residue was dissolved in 5 cm 3 of acetone and then acidified with 3 cm 3 of a 1N hydrogen chloride solution in diethyl ether. The resulting suspension was diluted with 20 cm 3 of diethyl ether, stirred at 20 ° C. for 3 hours, filtered, washed with diethyl ether and dried under reduced pressure (0.1 kPa) at 40 ° C. in a drier. 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (cyclopentylthioethyl) piperidine-4 0.4 g of -yl] methanol dihydrochloride were obtained in the form of a pale yellow solid (melting point 120 ° C.).
    [3624] 1 H NMR spectrum (CD 3 ) 2 SO-d 6 , δ (ppm) dropwise adding CD 3 COOD-d 4 as a small drop at a temperature of 400 MHz, 373K: 1.20 to 2.15 (mt: 16H); 2.93 (broad t, J = 7.5 Hz: 2H); 3.10 to 3.30 (mt: 7H); 3.33 (broad s: 2H); 3.91 (s: 3 H); 5.49 (mt: 1 H); 7.41 (dd, J = 9 and 3 Hz: 1H); 7.93 (d, J = 9 Hz: 1 H); 8.22 (d, J = 3 Hz: 1H); 8.60 (s: 1 H).
    [3625] {4- [3- (3-Chloro-6-methoxyquinolin-4-yl) -3- (R, S) -hydroxypropyl] piperidin-4-yl} methanol dihydrochloride
    [3626] Tert-butyl 4- (tert-butyldimethylsilanyloxymethyl) -4- [3- (3-chloro-6-methoxy-quinoline-in 6.5 cm 3 of 5N hydrochloric acid dissolved in dioxane and 30 cm 3 of dioxane A mixture of 1.5 g of 4-yl) -3- (R, S) -hydroxypropyl] piperidine-1-carboxylate was stirred at 20 ° C. for 17 hours. 100 cm 3 of diethyl ether was added to the reaction mixture. The precipitate formed is filtered to give {4- [3- (3-chloro-6-methoxyquinolin-4-yl) -3- (R, S) -hydroxy-propyl] piperidin-4-yl} methanol 1.24 g of dihydrochloride were obtained in the form of a pale yellow solid.
    [3627] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.20 to 2.10 (mt: 8H); 2.85 to 3.10 (mt: 4H); 3.26 (broad s: 2H); 3.91 (s: 3 H); 5.45 (mt: 1 H); 7.47 (dd, J = 9 and 3 Hz: 1 H); 7.98 (d, J = 9 Hz: 1 H); 8.23 (d, J = 3 Hz: 1H); 8.60 to 8.80 (unseparated peaks: 2H); 8.69 (s: 1 H).
    [3628] Tert-butyl 4- (tert-butyldimethylsilanyloxymethyl) -4- [3- (3-chloro-6-methoxyquinolin-4-yl) -3- (R, S) -hydroxy- Propyl] piperidine-1-carboxylate
    [3629] Tert-butyl 4- (tert-butyldimethylsilanyloxymethyl) -4- [3- (3-chloro-6-methoxyquinolin-4-yl in 300 cm 3 of dimethyl sulfoxide and 75 cm 3 of tert-butanol A solution of 5.26 g of) propyl] piperidine-1-carboxylate was stirred at 20 ° C. under an oxygen saturated atmosphere. After 5 minutes, a solution in which 2.1 g of tert-butoxide was dissolved in 30 cm 3 of tert-butanol was added to the reaction mixture. After oxygen cleaning for 1 hour 30 minutes, the reaction mixture was carefully poured onto a mixture of 300 g ice, 300 cm 3 water and 1.1 cm 3 acetic acid. The aqueous phase was extracted three times with 300 cm 3 of dichloromethane. The combined organic phases were washed twice with 300 cm 3 of water, dried over magnesium sulfate and concentrated to dryness at 40 ° C. under reduced pressure (2 kPa). The residue obtained was purified by chromatography under a 50 kPa nitrogen pressure on a silica gel column (particle size 20-45 μ; diameter 4 cm; height 27 cm) eluted with a cyclohexane / ethyl acetate mixture (50/50 volume ratio). Fractions containing the expected product were combined and concentrated to dryness under the above conditions. Tert-butyl 4- (tert-butyldimethylsilanyloxymethyl) -4- [3- (3-chloro-6-methoxy-quinolin-4-yl) -3-hydroxypropyl] piperidine- 3.4 g of 1-carboxylate were obtained in the form of a white foam.
    [3630] Mass spectrum: EI m / z = 578 M +
    [3631] m / z = 521 C 26 H 38 ClN 2 O 5 Si +
    [3632] m / z = 465 C 22 H 30 ClN 2 O 5 Si +
    [3633] m / z = 421 C 21 H 30 ClN 2 O 3 Si + Reference Peak
    [3634] m / z = 57 C 4 H 9 +
    [3635] DCI m / z = 579MH +
    [3636] m / z = 523 C 26 H 40 ClN 2 O 5 Si +
    [3637] Tert-butyl 4- (tert-butyldimethylsilanyloxymethyl) -4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] piperidine-1-carboxylate
    [3638] Tert-butyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -4-hydroxymethyl-piperidine-1-carboxylate in dichloromethane 20 cm 3 0.45 g, 3 A mixture of 0.3 g of tert-butyldimethylsilyl chloride, 0.17 cm 3 of triethylamine and 0.04 g of dimethylaminopyridine was stirred at 20 ° C. under an inert atmosphere. After stirring for 18 hours, 0.3 g tert-butyldimethylsilyl chloride, 0.04 g dimethylaminopyridine and 0.2 cm 3 of triethylamine were added. The reaction mixture was dissolved in 20 cm 3 of water. The aqueous phase was extracted twice with 20 cm 3 of dichloromethane. The combined organic phases were washed twice with 300 cm 3 of saturated sodium chloride solution, dried over magnesium sulfate and concentrated to dryness at 40 ° C. under reduced pressure (2 kPa). The residue obtained was purified by chromatography under a 50 kPa nitrogen pressure on a silica gel column eluting with a cyclohexane / ethyl acetate mixture (70/30 volume ratio) (particle size 20-45 μ; diameter 2.5 cm; height 15 cm). Fractions containing the expected product were combined and concentrated to dryness under the conditions described above. Tert-butyl 4- (tert-butyldimethylsilanyloxymethyl) -4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] piperidine-1-carboxylate 0.48 g Was obtained in the form of a colorless lacquer.
    [3639] ' H NMR Spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): -0.04 (s: 6H); 0.76 (s: 9 H); 1.29 (mt: 4H); 1.39 (s: 9 H); 1.58 (mt: 4H); 3.19 (mt: 2 H); 3.20 to 3.45 (mt: 6H); 3.95 (s: 3 H); 7.41 (d, J = 3 Hz: 1H); 7.45 (dd, J = 9 and 3 Hz: 1H); 7.95 (d, J = 9 Hz: 1H); 8.67 (s: 1 H).
    [3640] Tert-butyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -4-hydroxymethylpiperidine-1-carboxylate
    [3641] Ethyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- (tert-butyloxycarbonyl) -piperidine-4-carboxylate in 250 cm 3 of tetrahydrofuran 1.05 g of lithium aluminum hydride was added in portions at -20 ° C under inert atmosphere with stirring to 12.3 g of solution. After stirring at 20 ° C. for 2 hours, 0.5 g of lithium aluminum hydride was added to the reaction mixture at −20 ° C. After 1 hour 30 minutes, the reaction mixture was cooled to 0 ° C. and hydrolyzed by addition of 1.8 cm 3 water, 1.3 cm 5N sodium hydride and 5.7 cm 3 water. After stirring at 20 ° C. for 30 minutes, the reaction mixture was filtered and washed with 400 cm 3 of ethyl acetate. The filtrate was washed with 200 cm 3 of saturated sodium chloride solution, dried over magnesium sulfate and concentrated to dryness under reduced pressure (2 kPa) at 40 ° C. 10.9 g of tert-butyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -4-hydroxy-methylpiperidine-1-carboxylate was obtained.
    [3642] ' H NMR Spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.23 (mt: 2H); 1.32 (mt: 2 H); 1.39 (s: 9 H); 1.58 (mt: 4H); 3.10 to 3.40 (mt: 6H); 3.22 (d, J = 5 Hz: 2H); 3.96 (s: 3 H); 4.50 (t, J = 5 Hz: 1 H); 7.40 (d, J = 3 Hz: 1H); 7.45 (dd, J = 9 and 3 Hz: 1H); 7.96 (d, J = 9 Hz: 1H); 8.68 (s: 1 H).
    [3643] Ethyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- (tert-butyloxycarbonyl) piperidine-4-carboxylate was prepared in Example 5. .
    [3644] Example 20
    [3645] 4- [3- (3-Chloro-6-methoxyquinolin-4-yl) -3- (R, S) -fluoropropyl] -1- (3-phenylpropyl) piperidine-4-carboxylic acid
    [3646] Methyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -3- (R, S) -fluoropropyl] -1- (3-phenylpropyl) pi in 8 cm 3 of 5N hydrochloric acid aqueous solution The mixture of ferridine-4-carboxylate was maintained at 100 ° C. for 6 hours with stirring. After stirring for 18 h at 20 ° C., the reaction mixture was concentrated to dryness at 40 ° C. under reduced pressure (2 kPa). The obtained residue was dissolved in 10 cm 3 of dichloromethane and filtered. The filtrate was concentrated to dryness as described above, dissolved in diisopropyl ether and dried under reduced pressure (0.1 kPa) at 40 ° C. in a drier. The obtained residue was purified by chromatography under 60 kPa nitrogen pressure on a silica gel column eluting with a dichloromethane / methanol / aqueous ammonia (83/15/2) mixture (particle size 20 to 45μ; diameter 2.5cm; height 40cm). Fractions 13-20 were combined and concentrated to dryness under the conditions described above. 4- [3- (3-Chloro-6-methoxyquinolin-4-yl) -3- (R, S) -fluoropropyl] -1- (3-phenylpropyl) piperidine-4-carboxylic acid 0.24 g was obtained in the form of a white solid (melting point 240 ° C.).
    [3647] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.20 to 2.35 and 2.40 to 2.70 (mts: total 18 H); 3.94 (broad s: 3H); 6.36 (2 mts, J HF = 48 Hz: 1 H); 7.10 to 7.35 (mt: 5H); 7.52 (broad d, J = 9 Hz: 1H); 7.57 (broad s: 1H); 8.02 (broad d, J = 9 Hz: 1H); 8.75 (broad s: 1H).
    [3648] Methyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -3- (R, S) -fluoropropyl] -1- (3-phenylpropyl) piperidine-4-carboxyl Rate
    [3649] Methyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -3- (R, S) -hydroxypropyl] -1- (3-phenylpropyl) piperi in 40 cm 3 of dichloromethane 0.31 cm 3 of diethylaminosulfur trifluoride was added at −15 ° C. under inert atmosphere while stirring the solution in which 0.66 g of dean-4-carboxylate was dissolved. Then, after stirring at 20 ° C. for 3 hours, 0.31 cm 3 of diethylaminosulfur trifluoride was added to the reaction mixture, followed by 20 cm 3 of saturated sodium hydrogen carbonate solution. The aqueous phase was extracted with 20 cm 3 of dichloromethane. The organic phases were combined, washed with saturated sodium chloride solution, dried over magnesium sulfate and concentrated to dryness at 40 ° C. under reduced pressure (2 kPa). The obtained residue was purified by chromatography under a 100 kPa nitrogen pressure on a silica gel column eluting with a dichloromethane / methanol mixture (97/3) (particle size 20 to 45μ; diameter 3.5cm; height 35cm). Fractions 15-21 were combined and concentrated to dryness under the conditions described above. Methyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -3- (R, S) -fluoropropyl] -1- (3-phenylpropyl) piperidine-4-carboxyl 0.5 g of a rate was obtained in the form of a brown oil.
    [3650] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.30 to 2.35 and 2.50 to 2.80 (mts: total 18 H); 3.54 (s: 3 H); 3.93 (s: 3 H); 6.36 (ddd, J HF = 48-8.5 and 4.5 Hz: 1H); 7.19 (mt: 3 H); 7.29 (broad t, J = 7.5 Hz: 2H); 7.52 (mt: 2 H); 8.04 (d, J = 9 Hz: 1H); 8.75 (broad s: 1H).
    [3651] Methyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -3- (R, S) -hydroxypropyl ] -1- (3-phenylpropyl) piperidine-4- Carboxylate
    [3652] 1 g of methyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -3- (R, S) -hydroxypropyl] piperidine-4-carboxylate in 50 cm 3 of acetonitrile A mixture of 0.58 g bromo-3-phenylpropane and 0.53 g potassium carbonate was heated at 75 ° C. for 22 hours under inert atmosphere with stirring. Then, after cooling to 20 ° C., the reaction mixture was filtered and washed with acetonitrile. The filtrate was concentrated to dryness at 40 ° C. under reduced pressure (2 kPa). The residue obtained was purified by chromatography under a 100 kPa nitrogen pressure on a silica gel column eluting with a dichloromethane / methanol mixture (95/5) (particle size 70-200 μm; diameter 3.5 cm; height 40 cm). Fractions 21 to 48 were combined and concentrated to dryness under the conditions described above. Methyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -3- (R, S) -hydroxypropyl] -1- (3-phenylpropyl) piperidine-4-carboxyl 0.7 g of rate were obtained.
    [3653] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.20 to 2.35 and 2.45 to 2.75 (mts: total 18 H); 3.48 (s: 3 H); 3.88 (s: 3 H); 5.40 (mt: 1 H); 6.07 (d, J = 4 Hz: 1H); 7.20 to 7.25 (mt: 3H); 7.27 (broad t, J = 7.5 Hz: 2H); 7.44 (dd, J = 9 and 3 Hz: 1H); 9.96 (d, J = 9 Hz: 1H); 8.14 (d, J = 3 Hz: 1H); 8.66 (s: 1 H).
    [3654] Methyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -3- (R, S) -hydroxypropyl] piperidine-4-carboxylate was prepared in Example 49.
    [3655] Example 21
    [3656] Benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino) ethyl] -piperidine-4-carboxyl The rate was prepared in the form of a yellow oil.
    [3657] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.35 to 1.60 (mt: 4H); 1.74 (mt: 2 H); 1.95 to 2.10 (mt: 4H); 2.40 (t, J = 7 Hz: 2H); 2.60 to 2.75 (mt: 2H); 3.07 (mt: 2 H); 3.15 (broad t, J = 7.5 Hz: 2H); 3.94 (s: 3 H); 5.05 (s: 2 H); 6.05 (broad t, J = 5 Hz: 1H); 6.15 to 6.30 (mt: 3H); 7.27 (mt: 5 H); 7.36 (d, J = 2.5 Hz: 1 H); 7.47 (dd, J = 9 and 2.5 Hz: 1H); 7.98 (d, J = 9 Hz: 1 H); 8.68 (s: 1 H).
    [3658] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino) ethyl] piperidine-4-carboxylic acid
    [3659] Benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino) ethyl] piperi in 12 cm 3 of 5N hydrochloric acid aqueous solution A mixture of 0.73 g of din-4-carboxylate was maintained at 100 ° C. for 3.5 hours with stirring. After cooling to about 20 ° C., the reaction mixture was evaporated at 50 ° C. under reduced pressure (2 kPa). The evaporated residue obtained was dissolved in 50 cm 3 of acetone and then concentrated to dryness under the same conditions as described above. The resulting foam was purified by chromatography under 50 kPa argon pressure on a silica gel column (particle size 20-45 μ; diameter 2.5 cm; height 38 cm) eluted with a chloroform / methanol / aqueous ammonia (12/3 / 0.5 volume ratio) mixture. Fractions 31 to 46 were combined and concentrated to dryness under the conditions as described above. The powder obtained was dried in an oven at 40 ° C. under reduced pressure (0.1 kPa). 0.28 g of 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenylamino) ethyl] piperidine-4-carboxylic acid Obtained in the form of a white pink solid (melting point 210 ° C.).
    [3660] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.45 (broad t, J = 12.5 Hz: 2H); 1.56 (mt: 2 H); 1.68 (mt: 2 H); 1.90 to 2.10 (mt: 4H); 2.41 (t, J = 6.5 Hz: 2H); 2.66 (broad d, J = 12 Hz: 2H); 3.08 (mt: 2 H); 3.18 (broad t, J = 7.5 Hz: 2H); 3.97 (s: 3 H); 6.08 (broad t, J = 4.5 Hz: 1H); 6.15 to 6.30 (mt: 3H); 7.38 (d, J = 2.5 Hz: 1 H); 7.45 (dd, J = 9 and 2.5 Hz: 1H); 7.96 (d, J = 9 Hz: 1 H: 1 H); 8.68 (s: 1 H).
    [3661] Example 22
    [3662] 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-3-yl) thioethyl] py Ferridin-4-yl methanol
    [3663] {4- [3- (3-chloro-6-methoxyquinolin-4-yl) -3- (R, S) -hydroxypropyl] piperidin-4-yl} methanol dihydro in 25 cm 3 of acetonitrile A mixture of 0.6 g chloride, 0.34 g 2- (2-bromo-ethylthio) thiophene, 0.95 g potassium carbonate and 0.23 g potassium iodide was heated for 17 h at 80 ° C. under inert atmosphere with stirring. After cooling to 20 ° C., the reaction mixture was diluted with 30 cm 3 of water and then extracted twice with 30 cm 3 of ethyl acetate. The combined organic extracts were dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa) at 40 ° C. The resulting oil was purified by chromatography under 50 kPa argon pressure on a silica gel column (particle size 20-45 μ; diameter 3 cm; height 27 cm) eluting with a dichloromethane / methanol (93/7 volume ratio) mixture. Fractions containing product were combined and concentrated to dryness under the conditions described above. The oil obtained was acidified with 2 cm 3 of 1N hydrogen chloride ether, diluted with 20 cm 3 of diethyl ether and stirred at 20 ° C. for 1 hour. The solid was filtered off, washed with diethyl ether and dried under reduced pressure (10 kPa) in an oven at 40 ° C. 4- [3- (R, S) -hydroxy-3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2-thien-3-yl) thioethyl] -py 0.28 g of ferridin-4-yl} methanol hydrochloride was obtained in the form of a yellow solid (melting point 118 ° C.) but turned into a paste.
    [3664] 1 H NMR spectrum (400 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)). A mixture of two diastereomers of about 50/50 ratio was observed.
    [3665] * 1.35 to 2.10 (mt: 8H); 2.85 to 3.60 (mt: 10H); 3.86 and 3.87 (2s: 3H total); 5.41 (mt: 1 H); 5.80 to 6.30 (broad unseparated peak: 1H); 7.10 (mt: 1 H); 7.29 (mt: 1 H); 7.43 (dd, J = 9 and 3 Hz: 1H); 7.70 (mt: 1 H); 7.94 (d, J = 9 Hz: 1H); 8.19 (broad s: 1H); 8.64 (s: 1 H); 9.48 (unisolated peak: 1H).
    [3666] {4- [3- (3-Chloro-6-methoxyquinolin-4-yl) -3- (R, S) -hydroxypropyl] piperidin-4-yl} methanol dihydrochloride was prepared in Example 19. Prepared in.
    [3667] Example 23
    [3668] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl) piperidine-4-carboxamide
    [3669] 0.75 g of 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl) piperidine-4-carboxylic acid in the sodium salt form in 20 cm 3 of dichloromethane To the mixture was added 15.6 cm 3 of 0.5N aqueous ammonia solution in dioxane, 0.26 g of 1-hydroxybenzotriazole hydrate, 0.75 g of 1- [3- (dimethylamino) propyl] -3-ethylcarbodiimide hydrochloride and 0.55 triethylamine. Cm 3 was added. The resulting suspension was stirred at 20 ° C. for 17 hours. The reaction mixture was diluted with 25 cm 3 of water, stirred and then allowed to settle by phase separation. The aqueous phase was extracted twice with 25 cm 3 of dichloromethane and the combined organic extracts were washed with 25 cm 3 of brine and then dried over magnesium sulfate and concentrated to dryness at 40 ° C. under reduced pressure (2 kPa). The evaporated residue obtained was purified by chromatography under a 50 kPa argon pressure on a silica gel column (particle size 20 to 45μ; diameter 3cm; height 21cm) eluting with a dichloromethane / methanol (90/10 volume ratio) mixture. Fractions containing product were combined and concentrated to dryness under the conditions described above. 0.22 g of 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl) -piperidine-4-carboxamide were obtained in the form of a white solid. (Melting point 160 ° C).
    [3670] 1 H NMR spectrum (400 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.33 (broad t, J = 12 Hz: 2H); 1.53 (mt: 2 H); 1.67 (mt: 4H); 1.98 (mt: 4H); 2.20 (t, J = 7.5 Hz: 2H); 2.40 to 2.60 (mt: 4H); 3.15 (t, J = 7.5 Hz: 2H); 3.97 (s: 3 H); 6.87 (s: 1 H); 7.10 (s: 1 H); 7.17 (mt: 1 H); 7.20 (broad d, J = 7.5 Hz: 2H); 7.27 (broad t, J = 7.5 Hz: 2H); 7.37 (d, J = 2.5 Hz: 1 H); 7.45 (dd, J = 9 and 2.5 Hz: 1H); 7.96 (d, J = 9 Hz: 1H); 8.68 (s: 1 H).
    [3671] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- (3-phenylpropyl) piperidine-4-carboxylic acid dihydrochloride was prepared in Example 4.
    [3672] Example 24
    [3673] 4- [3- (3-chloro-6,7-dimethoxyquinolin-4-yl) propyl] -1- [2- (thiophen-2-ylthio) ethyl] piperidine-4-carboxylic acid
    [3674] Ethyl 4- [3- (3-chloro-6,7-dimethoxyquinolin-4-yl) propyl] -1- [2- (thiophen-2-ylthio) ethyl] piperidine in 20 cm 3 of dioxane To a solution of 1.47 g of 4-carboxylate was added 26 cm 3 of 5N aqueous sodium hydroxide solution and 20 cm 3 of methanol under stirring at a temperature of 20 ° C., and the mixture was then maintained at about 70 ° C. for 21 hours. The reaction mixture was concentrated to dryness at 40 ° C. under reduced pressure (2 kPa). The residue obtained was purified by chromatography under a 50 kPa argon pressure on a silica gel column (particle size 40 to 63 μ; mass 60 g) eluted with a dichloromethane / methanol / aqueous ammonia (12/3 / 0.5 volume ratio) mixture. Fractions 11-25 were combined and concentrated to dryness under the conditions described above. 4- [3- (3-Chloro-6,7-dimethoxyquinolin-4-yl) -propyl] -1- [2- (thiophen-2- ylthio) ethyl] piperidine-4-carboxylic acid 1.03 g was obtained in the form of a white solid (melting point 214 ° C.).
    [3675] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.27 (very broad t, J = 12 Hz: 2H); 1.45 to 1.75 (mt: 4H); 1.85 to 2.10 (mt: 4H); 2.44 (mt: 2 H); 2.50 to 2.65 (mt: 2H); 2.89 (broad t, J = 7.5 Hz: 2H); 3.13 (mt: 2 H); 3.93 (s: 3 H); 3.96 (s: 3 H); 7.02 (dd, J = 5.5 and 3.5 Hz: 1H); 7.15 (dd, J = 3.5 and 1 Hz: 1H); 7.30 (broad s: 1 H); 7.38 (broad s: 1H); 7.58 (dd, J = 5.5 and 1 Hz: 1H); 8.58 (s: 1 H).
    [3676] Ethyl 4- [3- (3-chloro-6,7-dimethoxyquinolin-4-yl) propyl] -1- [2- (thiophen-2-ylthio) ethyl] piperidine-4-carboxylate
    [3677] 1.65 g of ethyl 4- [3- (3-chloro-6,7-dimethoxyquinolin-4-yl) piperidine-4-carboxylate in acetonitrile 50 cm 3, 2- (2-bromoethylthio) thi A mixture of 1.16 g of fen, 1.63 g of potassium carbonate and 0.685 g of potassium iodide was stirred at 20 ° C. for 23 hours. This suspension was filtered and the filtrate was concentrated to dryness at 40 ° C. under reduced pressure (2 kPa). The evaporated residue was dissolved in 50 cm 3 of ethyl acetate, washed twice with 50 cm 3 of water and 40 cm 3 of saturated aqueous sodium chloride solution, dried over magnesium sulfate, filtered and concentrated to dryness under the above conditions. The resulting oil was purified by chromatography under 50 kPa argon pressure on a silica gel column (particle size 40-63 μ; diameter 4 cm) eluting with a dichloromethane / methanol / acetonitrile (95 / 2.5 / 2.5 volume ratio) mixture. Fractions containing product were combined and concentrated to dryness at 40 ° C. under reduced pressure (2 kPa). 4- [3- (3-chloro-6,7-dimethoxyquinolin-4-yl) propyl] -1- [2- (thiophen-2-ylthio) ethyl] -piperidine-4-carboxylic acid 1.47 g was obtained in the form of an oil.
    [3678] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.05 (t, J = 7 Hz: 3H); 1.37 (broad t, J = 12 Hz: 2H); 1.52 (mt: 2 H); 1.60 to 1.75 (mt: 2H); 1.85 to 2.05 (mt: 4H); 2.46 (mt: 2 H); 2.61 (broad d, J = 12 Hz: 2H); 2.91 (mt: 2 H); 3.15 (broad t, J = 7.5 Hz: 2H); 3.95 (s: 3 H); 3.97 (s: 3 H); 4.00 (q, J = 7 Hz: 2H); 7.04 (dd, J = 5.5 and 3.5 Hz: 1H); 7.17 (dd, J = 3.5 and 1 Hz: 1H); 7.31 (broad s: 1H); 7.40 (broad s: 1H); 7.60 (dd, J = 5.5 and 1 Hz: 1H); 8.61 (s: 1 H).
    [3679] Ethyl 4- [3- (3-chloro-6,7-dimethoxyquinolin-4-yl) -piperidine-4-carboxylate
    [3680] Ethyl 4- [3- (3-chloro-6,7-dimethoxyquinolin-4-yl) propyl] -1- (tert-butyloxycarbonyl) piperidine-4-carboxylate in 20 cm 3 of dichloromethane 3 cm 3 of trifluoroacetic acid was added dropwise at a temperature of 20 ° C. while stirring 2.05 g of the mixture. After 2 hours the reaction mixture was concentrated to dryness at 40 ° C. under reduced pressure (2 kPa). The residue was dissolved in 20 cm 3 of water and 10 cm 3 of ethyl acetate and then extracted twice with 10 cm 3 of aqueous 1N hydrochloric acid solution. The aqueous phase was basified with 30% aqueous sodium hydroxide solution until the pH was about 10, and then extracted three times with 30 cm 3 of ethyl acetate. The organic extracts were combined and dried over magnesium sulfate, filtered and concentrated to dryness as described above. 1.65 g of ethyl 4- [3- (3-chloro-6,7-dimethoxyquinolin-4-yl) piperidine-4-carboxylate were obtained in the form of a yellow oil.
    [3681] Mass spectrum: EI m / z = 420 M + m / z = 364 C 19 H 23 ClNO 4 +
    [3682] m / z = 264 C 14 H 15 ClNO 2 + m / z = 237
    [3683] C 12 H 12 ClNO 2 + Reference Peak
    [3684] m / z = 184 C 10 H 18 NO 2 +
    [3685] Ethyl 4- [3- (3-chloro-6,7-dimethoxyquinolin-4-yl) propyl] -1- (tert-butyloxycarbonyl) piperidine-4-carboxylate
    [3686] 21 cm 3 of 0.5M 9-borabicyclo [3.3.1] nonane solution was cooled to 0 ° C. and ethyl 4-allyl-1- in 26 cm 3 of tetrahydrofuran while maintaining a temperature of about 0 ° C. under inert atmosphere with stirring. 2.61 g of (tert-butyloxycarbonyl) -piperidine-4-carboxylate was added dropwise. After addition, the temperature of the mixture is reduced to about 20 ° C. The resulting solution was further stirred for 4 hours at this temperature, followed by 37 cm 3 of dioxane, 0.19 g of palladium diphenylphosphinoferrocene chloride, 3.05 g of 4-bromo-3-fluoro-6-methoxyquinoline and trivalent 5.58 g of potassium phosphate was added. After stirring at 60 ° C. for 24.75 hours, the reaction mixture was cooled to about 20 ° C. and filtered, and the filtrate was concentrated to dryness at 40 ° C. under reduced pressure (2 kPa). The obtained residue was dissolved in 100 cm 3 of ethyl acetate and 100 cm 3 of water, precipitated and phase separated, and the organic phase was washed with 100 cm 3 of saturated sodium chloride solution. The organic phase was dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa) at 40 ° C. temperature. The oil obtained was purified by chromatography under 50 kPa argon pressure on a silica gel column (particle size 40 to 63 μ; volume 690 cm 3) eluted with a dichloromethane / methanol / acetonitrile mixture (98/1/1 volume ratio) mixture. Fractions containing product were combined and concentrated to dryness under the conditions described above. 2.16 g of ethyl 4- [3- (3-chloro-6,7-dimethoxyquinolin-4-yl) propyl] -1- (tert-butyloxycarbonyl) piperidine-4-carboxylate yellow gel Obtained in form.
    [3687] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.06 (t, J = 7 Hz: 3H); 1.25 to 1.45 (mt: 2H); 1.39 (s: 9 H); 1.53 (mt: 2 H); 1.69 (mt: 2 H); 1.93 (broad d, J = 13.5 Hz: 2H), 2.82 (unisolated peak: 2H); 3.14 (broad t, J = 7.5 Hz: 2H); 3.69 (broad d, J = 13.5 Hz: 2H); 3.94 (s: 3 H); 3.97 (s: 3 H); 4.03 (q, J = 7 Hz: 2H); 7.31 (broad s: 1H); 7.40 (broad s: 1H); 8.61 (s: 1 H).
    [3688] 4-bromo-3-chloro-6,7-dimethoxyquinoline
    [3689] 19 g of triphenylphosphine dibromide were added at 20 ° C while stirring a solution in which 5.39 g of 3-chloro-4-hydroxy-6,7-dimethoxyquinoline was dissolved in 270 cm 3 of acetonitrile. The reaction mixture was heated to about 80 ° C. for 8.25 h. After cooling to 20 ° C., the insoluble material was filtered off. 5.67 g of 4-bromo-3-chloro-6,7-dimethoxyquinoline were obtained in the form of a gray solid.
    [3690] Mass spectrum: DCI m / z = 302 MH +
    [3691] 3-chloro-4-hydroxy-6,7-dimethoxyquinoline
    [3692] 5.45 g of N-chlorosuccinimide was added at 20 DEG C while stirring the solution of 6,7-dimethoxyquinolin-4-ol dissolved in 300 cm 3 of acetic acid. The reaction mixture was heated at 50 ° C. for 6 hours. After cooling to about 20 ° C. and stirring at this temperature for 18 hours, the reaction mixture was concentrated to dryness at 40 ° C. under reduced pressure (2 kPa). To the evaporated residue, 100 cm 3 of sodium hydrogen carbonate solution was added dropwise, and the suspension was stirred at a temperature of 20 ° C for 24 hours. The insoluble material was filtered off and dried in an oven under reduced pressure (20 Pa). 5.39 g of 3-chloro-4-hydroxy-6,7-dimethoxyquinoline were obtained in the form of a dark green solid.
    [3693] Mass spectrum: DCI m / z = 240 MH +
    [3694] 6,7-dimethoxy-4-hydroxyquinoline
    [3695] A mixture of 9.24 g of 4-hydroxy-6,7-dimethoxyquinoline-3-carboxylic acid in 185 cm 3 of diphenyl ether was maintained at 250 ° C. for 1.3 h under mechanical stirring. After the reaction mixture was cooled to about 20 ° C., 100 cm 3 of diisopropyl ether was added. After stirring this suspension for 8 hours and filtering, the filter cake was washed three times with 100 cm 3 of diisopropyl ether. 7.96 g of 6,7-dimethoxyquinolin-4-ol were obtained in the form of a brown solid.
    [3696] Infrared spectrum (KBr): 3242; 1605; 1548; 1500; 1273; 1239; 1220; 1075 and 822 cm -1
    [3697] 4-hydroxy-6,7-dimethoxyquinoline-3-carboxylic acid
    [3698] To this mixture of 21.1 g of diethyl 2-[(3,4-dimethoxyphenylamino) methylene] malonate in 42 cm 3 of nitrobenzene was carefully added 10.2 g of phosphorus pentoxide under mechanical stirring. The reaction mixture was maintained at 150 ° C. for 4 hours. After cooling to about 20 ° C. and stirring at this temperature for 18 hours, 14 cm 3 of water was added dropwise and the reaction mixture was heated to about 110 ° C. for 7 hours. After cooling to 20 ° C., 42 cm 3 of ethyl acetate was added. Under this condition, the suspension was stirred for 18 hours, allowed to settle by phase separation, the organic phase was filtered off, and the filter cake was washed three times with 40 cm3 of ethyl acetate, 40 cm3 of ethanol and 40 cm3 of water. 9.25 g of 4-hydroxy-6,7-dimethoxyquinoline-3-carboxylic acid were obtained in the form of a cream solid.
    [3699] Infrared spectrum (KBr): 2842; 1673; 1631; 1590; 1503; 1437; 1279; 1220; 1006; 807; 586 and 357 cm -1 .
    [3700] Diethyl 2-[(3,4-dimethoxyphenylamino) methylene] malonate
    [3701] A mixture of 10 g of 3,4-dimethoxyaniline in 13.2 cm 3 of diethyl ethoxymethylenemalonate was stirred at 110 ° C. for 1.5 h. After cooling to about 20 ° C., the reaction mixture was concentrated to dryness at 50 ° C. under reduced pressure (2 kPa). 21.1 g of diethyl 2-[(3,4-dimethoxyphenylamino) methylene] malonate were obtained in the form of a brown solid.
    [3702] Mass spectrum: DCI m / z = 324 MH +
    [3703] Ethyl 4-allyl-1- (tert-butyloxycarbonyl) -piperidine-4-carboxylate was prepared in Example 1
    [3704] Example 25
    [3705] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -3- (R, S) -hydroxypropyl] -1- [2- (2,5-difluorophenylthio) Ethyl] -piperidine-4-carboxylic acid monohydrochloride
    [3706] (R, S) -3- (3-chloro-6-methoxyquinolin-4-yl) -9- [2- (2,5-difluorophenylthio) -ethyl] -2- in 50 cm 3 of acetone To a solution in which 0.6 g of oxa-9-azaspiro [5.5] undecane-1-one was dissolved, 5 cm 3 of 5N aqueous sodium hydroxide solution was added at 20 ° C under stirring. After 2 h the reaction mixture was concentrated to dryness at 40 ° C. under reduced pressure (2 kPa). This evaporated residue was slurried in 10 cm 3 of diethyl ether, filtered and the filter cake was washed with diethyl ether and dried under reduced pressure (10 Pa) in an oven near 50 ° C. The solid was dissolved in water and acidified with 1N aqueous hydrochloric acid until pH was 3. Dichloromethane was added at 20 ° C. under moderate agitation and the solids were filtered off. 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -3- (R, S) -hydroxypropyl] -1- [2- (2,5-difluorophenylthio) 0.32 g of ethyl] piperidine-4-carboxylic acid monohydrochloride was obtained in the form of a white solid.
    [3707] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.30 to 2.35 (mt: 8H); 2.84 (unisolated peak: 2H); 3.05 to 3.70 (mt: 6H); 3.90 (broad s: 3H); 5.43 (unisolated peak: 1H); 6.16 (unisolated peak: 1H); 7.14 (unisolated peak: 1H); 7.33 (unisolated peak: 1H); 7.46 (mt: 2 H); 7.96 (broad d, J = 9 Hz: 1H); 8.16 (broad s: 1H); 8.67 (broad s: 1H); 10.20 to 10.60 (broad unseparated peak: 1H).
    [3708] 3- (3-chloro-6-methoxyquinolin-4-yl) -9- [2- (2,5-difluoro-phenylthio) ethyl] -2-oxa-9-azaspiro [5.5] Can-1-on
    [3709] Ethyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl)-(R, S) -propyl] piperidine-4-carboxylate di in 30 cm 3 of acetonitrile and 20 cm 3 of dimethylformamide A mixture of 1.75 g of hydrochloride, 0.95 g of 2- (2-bromoethylthio) -1,4-difluorobenzene, 0.62 g of potassium iodide and 3.11 g of potassium carbonate was heated under stirring at 85 ° C. for 18 hours. . After cooling to about 20 ° C., the reaction mixture was filtered through celite and the filtrate was concentrated to dryness at 40 ° C. under reduced pressure (2 kPa). The obtained residue was dissolved in water and diethyl ether. The organic phase was dried over magnesium sulfate, filtered and concentrated to dryness as described above. The resulting residue was purified by chromatography under atmospheric pressure on a silica gel column (particle size 70-200 μ; diameter 4 cm) eluting with a dichloromethane / methanol (97.5 / 2.5 volume ratio) mixture. Fractions containing product were combined and concentrated to dryness under the conditions described above. 3- (3-chloro-6-methoxyquinolin-4-yl) -9- [2- (2,5-difluorophenylthio) ethyl] -2-oxa-9-azaspiro [5.5] undecane 0.6 g of 1-one was obtained.
    [3710] Mass spectrum: EI m / z = 532 M + m / z = 373 C 20 H 22 ClN 2 O 3 +
    [3711] Reference peak
    [3712] 2- (2-Bromoethylthio) -1,4-difluorobenzene was prepared in Example 14.
    [3713] Methyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -3- (R, S) -hydroxypropyl] piperidine-4-carboxylate was prepared in Example 49.
    [3714] Example 26
    [3715] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -3- (R, S) -fluoropropyl] -1- [2- (3,5-difluorophenoxy) Ethyl] piperidine-4-carboxylate
    [3716] Methyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -3- (R, S) -fluoropropyl] -1- [2- (3,5 in 6.6 cm 3 of 5N aqueous hydrochloric acid solution A mixture of 0.4 g of difluorophenoxy) ethyl] piperidine-4-carboxylate was maintained at 100 ° C. under stirring for 6 hours. After cooling to about 20 ° C., the reaction mixture was stirred at this temperature for 20 hours and then concentrated to dryness at 40 ° C. under reduced pressure (2 kPa). The residue was dissolved in a dichloromethane / methanol mixture (90/10 volume ratio) and concentrated to dryness again under the above conditions. The evaporated residue was eluted with a dichloromethane / methanol / 28% aqueous ammonia mixture (83/15/2 volume ratio) and collected on 30 cm 3 fractions of silica gel column (particle size 40 to 60 μ; diameter 2.5 cm; height 41 cm) at 60 kPa argon pressure Purified by chromatography under. Fractions containing product were combined and concentrated to dryness under the conditions described above. Fractions 16-22 were combined and concentrated to dryness under the conditions described above. The residue was slurried in 10 cm 3 of diisopropyl ether, filtered off and dried. 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -3- (R, S) -fluoropropyl] -1- [2- (3,5-difluorophenoxy) 0.21 g of ethyl] -piperidine-4-carboxylic acid was obtained in the form of an off-white solid (melting point 205 ° C.).
    [3717] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.20 to 1.70 (mt: 3H); 1.80 to 2.40 (mt: 7H); 2.30 to 2.80 (mt: 2H); 2.61 (t, J = 6 Hz: 2H); 3.92 (s: 3 H); 4.17 (t, J = 6 Hz: 2H); 6.36 (d mt, J HF = 48 Hz: 1H); 6.65 to 6.85 (mt: 3H); 7.51 (dd, J = 9 and 2.5 Hz: 1H); 7.55 (broad s: 1H); 8.02 (d, J = 9 Hz: 1H); 8.74 (s: 1 H).
    [3718] Methyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -3- (R, S) -fluoropropyl] -1- [2- (3,5-difluorophenoxy Ethyl] piperidine-4-carboxylate
    [3719] Methyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -3- (R, S) -hydroxypropyl] -1- [2- (3,5- in 50 cm 3 of dichloromethane A solution in which 1.1 g of difluorophenoxy) ethyl] piperidine-4-carboxylate was dissolved was added 0.4 cm 3 of diethylaminosulfur trifluorolide at −10 ° C. under inert atmosphere while stirring. After stirring for 4 hours at 20 ° C., 0.4 cm 3 of diethylaminosulfur trifluoride was added to the reaction mixture, and the mixture was stirred at this temperature for 20 hours. 20 cm 3 saturated aqueous sodium hydrogen carbonate solution was added. The aqueous phase was extracted with 25 cm 3 of dichloromethane. The organic phase was washed with 25 cm 3 of 10% (by weight) aqueous sodium chloride solution, dried over magnesium sulfate and concentrated to dryness at 40 ° C. under reduced pressure (2 kPa). The oil obtained was eluted with a dichloromethane / methanol (97/3 volume ratio) mixture and purified by chromatography under a 100 kPa argon pressure on a silica gel column (particle size 40-60 μ; diameter 3.5 cm; height 35 cm), collected 35 cm 3 times. . Fractions 20 to 21 were combined and concentrated to dryness under the conditions described above. Methyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -3- (R, S) -fluoropropyl] -1- [2- (3,5-difluorophenoxy 0.62 g)) ethyl] -piperidine-4-carboxylate was obtained in the form of an orange oil.
    [3720] Infrared spectrum: (CH 2 Cl 2 ): 2953; 1725; 1622; 1599; 1504; 1466; 1234; 1152; 1117 and 837 cm -1 .
    [3721] Methyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -3- (R, S) -hydroxypropyl] -1- [2- (3,5-difluorophenoxy Ethyl] -piperidine-4-carboxylate
    [3722] 3- (3-chloro-6-methoxyquinolin-4-yl) -9- [2- (3,5-difluorophenoxy) ethyl] -2-oxa in 20 cm 3 of methanol cooled to −20 ° C. To a mixture of 1.1 g of -9-azaspiro [5.5] undecane-1-one was added dropwise 0.47 cm 3 of thionyl chloride under an inert atmosphere, and the mixture was stirred at a temperature of 20 ° C. for 24 hours. The reaction mixture was concentrated to dryness at 40 ° C. under reduced pressure (2 kPa). The residue was dissolved in 30 cm 3 of ethyl acetate and 15 cm 3 of water. After adding 5 g of potassium carbonate and vigorously stirring for 5 minutes, the mixture was allowed to settle to separate the organic phase and washed three times with 15 cm 3 of a 10% by weight aqueous sodium chloride solution. It was dried over magnesium sulfate, filtered and the organic solution was concentrated to dryness under reduced pressure (2 kPa) at 40 ° C. Methyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -3- (R, S) -hydroxypropyl] -1- [2- (3,5-difluorophenoxy 1.12 g)) ethyl] piperidine-4-carboxylate was obtained in the form of a brown lacquer.
    [3723] Infrared spectrum (CCl 4 ): 3615; 2952; 1732; 1622; 1600; 1466; 1233; 1154; 1117; 841 and 671 cm -1 .
    [3724] 3- (3-chloro-6-methoxyquinolin-4-yl) -9- [2- (3,5-difluorophenoxy) ethyl] -2-oxa-9-azaspiro [5.5] undecane -1-on
    [3725] 1 g of methyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -3- (R, S) -hydroxypropyl] piperidine-4-carboxylate in 45 cm 3 of acetonitrile A mixture of 0.8 g of-(2-bromoethoxy) -3,5-difluorobenzene and 0.42 g of potassium carbonate was kept for 20 hours at 80 ° C. under stirring and argon atmosphere. This suspension was filtered, the insoluble material was washed with ethyl acetate and the filtrate was concentrated to dryness at 40 ° C. under reduced pressure (2 kPa). The residue was purified by chromatography under 100 kPa argon pressure on a silica gel column (particle size 40-60 μ; diameter 3.5 cm; height 38 cm) eluting with a dichloromethane / methanol (97/3 volume ratio) mixture to collect 35-cm 3 fractions. . Fractions 9-20 were combined and concentrated to dryness under the conditions described above. 3- (3-chloro-6-methoxyquinolin-4-yl) -9- [2- (3,5-difluorophenoxy) ethyl] -2-oxa-9-azaspiro [5.5] -unde 1.1 g of cann-1-one were obtained.
    [3726] Infrared spectrum (CCl 4 ): 2940; 1735; 1622; 1600; 1503; 1467; 1233; 1153; 1117; 841 and 671 cm -1 .
    [3727] Methyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -3-hydroxypropyl] piperidine-4-carboxylate was prepared in Example 49.
    [3728] 1- (2-bromoethoxy) -3,5-difluorobenzene can be obtained by applying the method described in Example 16.
    [3729] Example 27
    [3730] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) ethyl] piperidine-4-carboxamide
    [3731] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (3,5-difluorophenoxy) ethyl] piperidine in 30 cm 3 of dichloromethane 13.4 cm <3> of 0.5N aqueous ammonia solution in dioxane, 0.229 g of 1-hydroxybenzotriazole hydrate, 1- [3- (dimethylamino) propyl] -3-ethyl, in an inert atmosphere with stirring to a mixture of 0.69 g of -4-carboxylic acids 0.64 g of carbodiimide hydrochloride and 0.46 cm 3 of triethylamine were added. The resulting suspension was stirred at 20 ° C. for 17 hours. The reaction mixture was diluted with 50 cm 3 of water, stirred and settled by precipitation. The aqueous phase was extracted twice with 25 cm 3 of dichloromethane, the combined organic extracts were washed with 25 cm 3 of saturated aqueous sodium chloride solution, dried over magnesium sulfate and concentrated to dryness at 40 ° C. under reduced pressure (2 kPa). The solid was dissolved in 20 cm 3 of diisopropyl ether, stirred and filtered. 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) ethyl] piperidine-4-carboxamide 0.52 g was obtained.
    [3732] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.34 (broad t, J = 12.5 Hz: 2H); 1.54 (mt: 2 H); 1.66 (mt: 2 H); 2.02 (broad d, J = 12.5 Hz: 2H); 2.12 (broad t, J = 11 Hz: 2H); 2.55 to 2.75 (mt: 4H); 3.16 (broad t, J = 7.5 Hz: 2H); 3.97 (s: 3 H); 4.08 (t, J = 6 Hz: 2H); 6.65 to 6.85 (mt: 3H); 6.91 (broad s: 1H); 7.15 (broad s: 1H); 7.37 (d, J = 3 Hz: 1H); 7.45 (dd, J = 9 and 3 Hz: 1H); 7.97 (d, J = 9 Hz: 1 H); 8.68 (s: 1 H).
    [3733] 4- [3- (3-Chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (3,5-difluorophenoxy) ethyl] piperidine-4-carboxylic acid Prepared in Example 2.
    [3734] Example 28
    [3735] Sodium salt of 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- (cinamyl) piperidine-4-carboxylic acid
    [3736] Ethyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- (cinnamil) piperidine- in 14 cm 3 of dioxane, 14 cm 3 of methanol and 14 cm 3 of 5N aqueous sodium hydroxide solution A mixture of 0.72 g of 4-carboxylate was stirred at 20 ° C. After 2 hours, 14 cm 3 of 5N aqueous sodium hydroxide solution was further added, and 14 cm 3 was further added after 18 hours. The reaction mixture was maintained at 70 ° C. for 21 hours. After cooling to about 20 ° C., the reaction mass was concentrated to dryness at 40 ° C. under reduced pressure (2 kPa). The obtained residue was dissolved in 15 cm 3 of distilled water, filtered and then dried in air for 18 hours. 0.49 g of sodium salt of 4- [4- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- (cinnamil) piperidine-4-carboxylic acid was obtained in the form of a white solid (melting point About 230 ° C.).
    [3737] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.16 (very broad t, J = 12 Hz: 2H); 1.45 to 1.70 (mt: 4H); 1.95 to 2.20 (mt: 4H); 2.45 to 2.60 (mt: 2H); 2.99 (d, J = 6.5 Hz: 2H); 3.14 (broad t, J = 7Hz: 2H); 3.99 (s: 3 H); 6.28 (dt, J = 15.5 and 6.5 Hz: 1H); 6.48 (d, J = 15.5 Hz: 1 H); 7.24 (broad t, J = 7.5 Hz: 1H); 7.33 (broad t, J = 7.5 Hz: 2H); 7.40 to 7.50 (mt: 4H); 7.95 (d, J = 9 Hz: 1H); 8.66 (s: 1 H).
    [3738] Ethyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- (cinamil) piperidine-4-carboxylate
    [3739] 1 g of ethyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate, 0.551 g of cinnamil bromide, 0.42 g of potassium iodide and 1.05 g of potassium carbonate The mixture mixed at 20 cm 3 of nitrile was stirred at 20 ° C. for 18.5 hours. The reaction mixture was filtered and the insoluble material was washed with 20 cm 3 of acetonitrile and then twice with 30 cm 3 of dichloromethane. The filtrate was dried over magnesium sulfate and then concentrated to dryness under reduced pressure (2 kPa) at 40 ° C. The residue obtained was purified by chromatography under a 50 kPa argon pressure on a silica gel column (particle size 40 to 63 μ; diameter 2.5 cm; mass 3 g) eluted with a cyclohexane / ethyl acetate mixture (90/10 volume ratio) and collected in 20 cm 3 fractions. It was. Fractions containing product were combined and concentrated to dryness under the conditions described above. 0.72 g of ethyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- (3-phenylallyl) piperidine-4-carboxylate was obtained in the form of a viscous orange oil. .
    [3740] Mass spectrum: EI m / z = 506 M +
    [3741] m / z = 415 C 23 H 28 ClN 2 O 3 +
    [3742] m / z = 300 C 19 H 26 NO 2 +
    [3743] m / z = 117 C 9 H 9 + reference peak
    [3744] Ethyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate was prepared in Example 5 in the monohydrochloride form.
    [3745] Example 29
    [3746] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) ethyl] piperidine-4-acetic acid
    [3747] Methyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5- in 10 cm 3 dioxane, 10 cm 3 methanol and 0.99 cm 3 5N aqueous sodium hydroxide solution A mixture of 0.18 g of difluorophenoxy) ethyl] piperidin-4-yl} carboxylate was stirred at 75 ° C. for 17 hours. After cooling to about 45 ° C., the reaction mixture was concentrated to dryness at 40 ° C. under pressure gradually decreasing to 9 kPa. The residue of the paste phase was dissolved in 3 cm 3 of chloroform / methanol / aqueous ammonia (12/3 / 0.5 volume ratio), and the organic phase was then eluted with a mixture of chloroform / methanol / aqueous ammonia (12/3 / 0.5 volume ratio). Elut: Purified by chromatography under atmospheric pressure on particle size 70-200μ; diameter 2cm; mass 5g). The fractions containing the product were combined and concentrated to dryness at 40 ° C. under reduced pressure (5 kPa), and the product was dried under reduced pressure (50 kPa) in an oven near 50 ° C. 0.15 g of 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) ethyl] piperidine-4-acetic acid Was obtained.
    [3748] ' H NMR Spectrum (500 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.39 (mt: 2H); 1.50 (mt: 2 H); 1.61 (mt: 4H); 2.15 (broad s: 2H); 2.30 to 2.60 (mt: 4H); 2.63 (broad t, J = 5.5 Hz: 2H); 3.12 (unisolated peak: 2H); 3.94 (s: 3 H); 4.06 (broad t, J = 5.5 Hz: 2H); 6.65 to 6.75 (mt: 3H); 7.36 (broad s: 1H); 7.41 (broad d, J = 9 Hz: 1H); 7.93 (d, J = 9 Hz: 1 H); 8.64 (s: 1 H).
    [3749] Methyl {4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) ethyl] piperidin-4-yl }acetate
    [3750] Methyl {4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] piperidin-4-yl} acetate 0.35 g, 1- (2-bromoethoxy) -3,5- A mixture of 0.318 g of difluorobenzene, 0.15 g of potassium iodide and 0.62 g of potassium carbonate was mixed in 20 cm 3 of acetonitrile was stirred at a temperature of 70 ° C. for 18 hours. After cooling to about 20 ° C., the reaction mixture was filtered through a silica cartridge (Bond Elut) and washed twice with 2 cm 3 of acetonitrile. The organic phase was concentrated to dryness at 45 ° C. under reduced pressure (2.4 kPa). The resulting evaporated residue was dissolved in 12 cm 3 of dimethylformamide and purified by injection of 3 cm 3 per chromatography four times onto a SCX silica gel cartridge (mass 1 g) gradient eluted from pure methanol to a 4N ammoniacal methanol mixture. Fractions containing product were combined and concentrated to dryness under pressurized air at a temperature of 45 ° C. The evaporated residue obtained was dissolved in dichloromethane and dried in air for 48 hours and then oven dried at 50 ° C. under reduced pressure (10 kPa). Methyl {4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) ethyl] piperidin-4-yl } 0.195 g of acetate were obtained.
    [3751] 1 H NMR spectrum (500 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)) at a temperature of 353K: 1.45 to 2.70 (mt: 16H); 3.17 (mt: 2 H); 3.51 (s: 3 H); 3.96 (s: 3 H); 4.24 (unseparated peak: 2H); 6.60 to 6.70 (mt: 3H); 7.38 (broad s: 1H); 7.42 (broad d, J = 9 Hz: 1H); 7.94 (d, J = 9 Hz: 1H); 8.62 (broad s: 1H).
    [3752] Methyl {4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -piperidin-4-yl} acetate
    [3753] Tert-butyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -4-cyanomethylpiperidine-1-carboxyl in 100 cm 3 of 12N hydrochloric acid solution (concentrated to dry) The mixture of rates was gradually raised to 100 ° C. under stirring for 18 hours. The reaction mixture was concentrated to dryness at 60 ° C. under reduced pressure (2 kPa). The oil obtained was dissolved in acetone and the precipitate was filtered off and washed with acetone. 20.4 g of {4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] piperidin-4-yl} acetic acid dihydrochloride were obtained in the form of a gray solid (melting point 181 ° C.) , Gradually became viscous. This product was dissolved in 400 cm 3 methanol and 10 cm 3 concentrated dry sulfuric acid, stirred, and heated at about 100 ° C. for 1.5 hours. The reaction mixture was concentrated to dryness at 50 ° C. under reduced pressure (2 kPa). The oil obtained was dissolved in 300 cm 3 of water under stirring, neutralized with sodium hydrogen carbonate, basified with potassium carbonate and extracted with ethyl acetate. The organic phase was separated after settling, washed with water, dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa) at 40 ° C. The aqueous phase was basified to pH 8 with 5N aqueous sodium hydroxide solution, extracted with ethyl acetate, precipitated, phase separated, washed with organic extracts, dried over magnesium sulfate and concentrated to dryness under the above conditions. All organic evaporation residues were combined and purified by chromatography under 50 kPa argon pressure on a silica gel column (particle size 20-43 μ; mass 200 g) eluted with a dichloromethane / methanol / aqueous ammonia mixture (40/5 / 0.5 volume ratio). Fractions containing product were combined and concentrated to dryness under the conditions described above. 7.6 g of methyl {4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] piperidin-4-yl} acetate were obtained in the form of an orange oil.
    [3754] Mass spectrum: EI m / z = 390 M + m / z = 207 C 11 H 10 ClNO +
    [3755] m / z = 184 C 10 H 18 NO 2 +
    [3756] Tert-butyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -4-cyanomethylpiperidine-1-carboxylate
    [3757] 30.58 g of tert-butyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -4-methanecellfonyloxymethylpiperidine-1-carboxylate at 436 cm 3 of dimethyl sulfoxide And a mixture of 15.1 g of potassium cyanide were heated under stirring at 100 ° C. for 48 hours and then stirred at 20 ° C. for 24 hours. 2000 cm 3 iced water was added to the reaction mixture, the suspension was stirred at 20 ° C. for 1 hour and then filtered, and the filter cake was washed three times with 200 cm 3 water and then dried in air. The residue was purified by chromatography under 50 kPa argon pressure on a silica gel column (particle size 20-45 μ; diameter 9 cm; height 45 cm) eluted with a cyclohexane / ethyl acetate mixture (90/10 volume ratio). Fractions 40-100 were combined and concentrated to dryness at 45 ° C. under reduced pressure (2 kPa). 19.25 g of tert-butyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -4-cyanomethyl-piperidine-1-carboxylate was obtained in the form of a yellow solid. (Melting point 160 ° C).
    [3758] Infrared spectrum (KBr): 2968; 2924; 2235; 1684; 1622; 1505; 1414; 1230; 1166; 1151; 826 and 738 cm -1 .
    [3759] Tert-butyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -4-methanesulfonyloxymethylpiperidine-1-carboxylate
    [3760] Tert-butyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -4-hydroxymethylpiperidine-1-carboxyl in 400 cm 3 of dichloromethane and 12.9 cm 3 of triethylamine The mixture of rate 24.8 g was cooled to about 0 ° C. under inert atmosphere with stirring. Methanesulfonyl chloride previously dissolved in 125 cm 3 of dichloromethane was added dropwise, and the reaction mixture was then stirred at a temperature of 20 ° C. for 18 hours. 200 cm 3 of water was added to the reaction mass followed by an additional 3000 cm 3 of water. Precipitate to settle by phase separation and extract the aqueous phase with 200 cm 3 of dichloromethane. The organic extract was washed with 300 cm 3 of aqueous sodium chloride solution, dried over sodium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa) at a temperature of 45 ° C. 30.6 g of tert-butyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -4-methanesulfonyloxymethylpiperidine-1-carboxylate in orangesec oil form Obtained.
    [3761] Mass spectrum: DCI / z = 507 MH +
    [3762] m / z = 431 M-CH 3 SO 3
    [3763] m / z = 397 431-Cl
    [3764] m / z = 375 431-tBu
    [3765] m / z = 331 431-BOC
    [3766] 1- (2-bromoethoxy) -3,5-difluorobenzene was prepared in Example 16.
    [3767] Tert-butyl 4- [3- (3-chloro-6-methoxy-quinolin-4-yl) propyl] -4-hydroxymethylpiperidine-1-carboxylate was prepared in Example 19.
    [3768] Example 30
    [3769] {4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,5-difluorophenoxy) ethyl] piperidin-4-yl} Acetic acid
    [3770] Methyl {4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,5 in 10 cm 3 dioxane, 10 cm 3 methanol and 1.91 cm 3 aqueous 5N sodium hydroxide solution A mixture of 0.35 g of difluorophenoxy) ethyl] piperidin-4-yl} acetate was stirred at 75 ° C. for 17 hours. After cooling to about 45 ° C., the reaction mixture was concentrated to dryness at 40 ° C. under pressure gradually decreasing to 9 kPa. The silica gel column (particles) was dissolved in 3 cm 3 of chloroform / methanol / aqueous ammonia (12/3 / 0.5 volume ratio) and the organic phase was eluted with a mixture of chloroform / methanol / aqueous ammonia (12/3 / 0.5 volume ratio). Purify by chromatography on atmospheric pressure from size 70 to 200μ; diameter 2cm; mass 5g). The fractions containing the product were combined and concentrated to dryness at 40 ° C. under reduced pressure (5 kPa), and the product was dried under reduced pressure (50 Pa) in an oven near 50 ° C. {4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,5-difluorophenoxy) ethyl] piperidin-4-yl} 0.27 g of acetic acid were obtained.
    [3771] ' H NMR Spectrum (500 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.39 (mt: 2H); 1.50 (mt: 2 H); 1.60 (mt: 4H); 2.15 (broad s: 2H); 2.30 to 2.60 (mt: 4H); 2.67 (t, J = 6 Hz: 2H); 3.12 (unisolated peak: 2H); 3.93 (s: 3 H); 4.12 (t, J = 6 Hz: 2H); 6.72 (mt: 1 H); 7.11 (mt: 1 H); 7.21 (mt: 1 H); 7.37 (broad s: 1H); 7.41 (broad d, J = 9 Hz: 1H); 7.93 (d, J = 9 Hz: 1 H); 8.64 (s: 1 H).
    [3772] Methyl {4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,5-difluorophenoxy) ethyl] piperidin-4-yl }acetate
    [3773] Methyl {4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] piperidin-4-yl} acetate 0.35 g, 2- (2-bromoethoxy) -1,4- A mixture of 0.32 g of difluorobenzene, 0.15 g of potassium iodide, and 0.62 g of potassium carbonate was mixed in 20 cm 3 of acetonitrile was stirred at a temperature of 70 ° C. for 18 hours. After cooling to about 20 ° C., the reaction mixture was filtered through a silica cartridge (Bond Elut) and washed twice with 2 cm 3 of acetonitrile. The organic phase was concentrated to dryness at 45 ° C. under reduced pressure (2.4 kPa). The resulting evaporated residue was dissolved in 12 cm 3 of dimethylformamide and purified by injection of 3 cm 3 per chromatography four times onto a SCX silica gel cartridge (mass 1 g) gradient eluted from pure methanol to a 4N ammoniacal methanol mixture. Fractions containing product were combined and concentrated to dryness under pressurized air at a temperature of 45 ° C. The evaporated residue obtained was dissolved in dichloromethane, dried for 48 hours in air and then oven dried at 50 ° C. under reduced pressure (10 Pa). Methyl {4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,5-difluorophenoxy) ethyl] piperidin-4-yl } 0.38 g of acetate were obtained.
    [3774] 1 H NMR spectrum (500 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.30 to 1.65 (mt: 8H); 2.25 (broad s: 2H); 2.30 to 2.60 (mt: 4H); 2.69 (mt: 2 H); 3.14 (mt: 2 H); 3.47 (broad s: 3H); 3.95 (broad s: 3H); 4.12 (mt: 2 H); 6.72 (mt: 1 H); 7.11 (mt: 1 H); 7.21 (mt: 1 H); 7.38 (broad s: 1H); 7.43 (broad d, J = 9 Hz: 1H); 7.94 (broad d, J = 9 Hz: 1H); 8.66 (broad s: 1H).
    [3775] 2- (2-bromoethoxy) -1,4-difluorobenzene was prepared in Example 16.
    [3776] Methyl {4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] piperidin-4-yl} acetate was prepared in Example 29.
    [3777] Example 31
    [3778] 1- (2-cyclopentylthioethyl) -4- [3- (3-fluoro-6-methoxy-quinolin-4-yl) propyl] piperidine-4-carboxylic acid
    [3779] Ethyl 1- (2-cyclopentylthioethyl) -4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl in 3 cm 3 dioxane, 3 cm 3 methanol and 2.4 cm 3 5N aqueous sodium hydroxide solution ] The mixture of 0.4 g of piperidine-4-carboxylate was stirred at 70 ° C. for 17 h. After cooling to about 20 ° C., the reaction mixture was concentrated to dryness under pressure gradually decreasing from 30 kPa to 2.5 kPa at 45 ° C. temperature. The residue was dissolved in 5 cm 3 of dichloromethane / methanol / aqueous ammonia (40/5 / 0.5 volume ratio) and then eluted with a dichloromethane / methanol / aqueous ammonia (40/5 / 0.5 volume ratio) mixture, followed by chloroform / methanol / Purification was performed by chromatography on a silica gel cartridge (Bond Elut; particle size 70-200μ; mass 10 g) eluting with an aqueous ammonia mixture (13/3 / 0.5). The fractions containing the precipitate were combined, filtered and washed with methanol. The resulting solid was recrystallized from 15 cm 3 of boiling methanol, cooled and then filtered, washed with methanol and oven dried at reduced pressure (10 Pa) at 20 ° C. The filtrates were combined and concentrated to dryness at 40 ° C. under reduced pressure (2 kPa). The concentrated and dried liquid once and the solid obtained above were combined to form 1- (2-cyclopentylthioethyl) -4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperi. 0.179 g of din-4-carboxylic acid was obtained in the form of a white solid.
    [3780] 1 H NMR spectrum (400 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm) added with a few drops of CF 3 COOD): 1.41 (mt: 2H); 1.50 to 1.75 (mt: 8H); 1.90 to 2.05 (mt: 4H); 2.20 (broad d, J = 14 Hz: 2H); 2.75 to 2.90 (mt: 4H); 3.10 to 3.25 (mt: 1 H); 3.16 (t, J = 7 Hz: 2H); 3.29 (mt: 2 H); 3.50 (broad d, J = 14 Hz: 2H); 3.99 (s: 3 H); 7.47 (d, J = 2.5 Hz: 1 H); 7.55 (dd, J = 9 and 2.5 Hz: 1H); 8.06 (d, J = 9 Hz: 1H); 8.98 (broad s: 1H).
    [3781] Ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -piperidine-4-carboxylate
    [3782] 0.5 g of ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate, 0.253 g of (2-chloroethylthio) cyclopentane, 0.25 i of potassium iodide g and 0.92 g of potassium carbonate were mixed in 15 cm 3 of acetonitrile and stirred at 70 ° C. for 18 hours. After cooling to about 20 ° C., the reaction mixture was filtered and washed twice with 3 cm 3 of acetonitrile. The organic phase was concentrated to dryness at 45 ° C. under reduced pressure (2.4 kPa). The resulting evaporated residue was dissolved in an ethyl acetate / 40 to 60 ° C. petroleum ether (8/2 volume ratio) mixture and then eluted with an ethyl acetate / 40 to 60 ° C. petroleum ether (8/2 volume ratio) mixture (Bond Elut Chromatographically purified under atmospheric pressure on particle size 70-200 μm; mass 10 g). Fractions 5-14 were combined and concentrated to dryness at 40 ° C. under reduced pressure (2 kPa). 0.43 g of ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate were obtained.
    [3783] 1 H NMR spectrum (500 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 0.98 (t, J = 7 Hz: 3H); 1.36 (mt: 4H); 1.40 to 1.70 (mt: 8H); 1.80 to 2.00 (mt: 6H); 2.30 to 2.65 (mt: 6H); 3.02 (mt: 2H); 3.09 (mt: 1 H); 3.92 (s: 3 H); 3.94 (q, J = 7 Hz: 2H); 7.31 (broad s: 1H); 7.37 (broad d, J = 9 Hz: 1H); 7.94 (d, J = 9 Hz: 1 H); 8.66 (broad s: 1H).
    [3784] Ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate was prepared in Example 11.
    [3785] Example 32
    [3786] 1- (2-cyclohexylethyl) -4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylic acid
    [3787] Ethyl 1- (2-cyclohexylethyl) -4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] in 3 cm 3 of dioxane, 3 cm 3 of methanol and 1.2 cm 3 of 5N aqueous sodium hydroxide solution. A mixture of 0.2 g of piperidine-4-carboxylate was stirred at 70 ° C. for 22 hours. After cooling to about 20 ° C., the reaction mixture was evaporated at 45 ° C. under pressure gradually decreasing from 30 kPa to 2.5 kPa. The residue was dissolved in 5 cm 3 of dichloromethane / methanol / aqueous ammonia (40/5 / 0.5 volume ratio) and then eluted with a dichloromethane / methanol / aqueous ammonia (40/5 / 0.5 volume ratio) mixture, followed by chloroform / methanol / Purification was performed by chromatography on a silica gel cartridge (Bond Elut; particle size 70-200μ; mass 10 g) eluting with an aqueous ammonia mixture (13/3 / 0.5). The fractions containing the product were combined, concentrated to dryness under reduced pressure (2 kPa) at 40 ° C. and then dried in a drier (10 kPa). 0.14 g of 1- (2-cyclohexylethyl) -4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylic acid was obtained in the form of a white solid.
    [3788] 1 H NMR spectrum (400 MHz, CF 3 COOD added with a few drops of (CD 3 ) 2 SO-d 6 , δ (ppm)): 0.80 to 1.00 (mt: 2H); 1.05 to 1.35 (mt: 5H); 1.40 to 1.75 (mt: 12H); 2.19 (broad d, J = 14 Hz: 2H); 2.78 (broad t, J = 12.5 Hz: 2H); 3.07 (mt: 2 H); 3.20 (broad t, J = 6.5 Hz: 2H); 3.45 (broad d, J = 12.5 Hz: 2H); 4.00 (s: 3 H); 7.52 (d, J = 2.5 Hz: 1H); 7.60 (dd, J = 9 and 2.5 Hz: 1H); 8.10 (d, J = 9 Hz: 1H); 9.10 (d, J = 2 Hz: 1 H).
    [3789] Ethyl 1- (2-cyclohexylethyl) -4- [3- (3-fluoro-6-methoxy-quinolin-4-yl) propyl] piperidine-4-carboxylate
    [3790] 0.4 g of ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate, 0.245 g of 1-bromo-2-cyclohexylethane, potassium iodide A mixture of 0.18 g and 0.737 g of potassium carbonate was mixed with 15 cm 3 of acetonitrile was stirred at 70 ° C. for 18 hours. After cooling to about 20 ° C., the reaction mixture was concentrated to dryness at 40 ° C. under reduced pressure (5 kPa). The resulting evaporated residue was purified by chromatography under atmospheric pressure on a silica gel cartridge (Bond Elut; particle size 70 to 200 μ; mass 12 g) eluted with a mixture of ethyl acetate / 40 to 60 ° C. petroleum ether (8/2 by volume). Fractions containing product were combined and concentrated to dryness at 40 ° C. under reduced pressure (2 kPa). 0.23 g of ethyl 1- (2-cyclohexylethyl) -4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate were obtained.
    [3791] ' H NMR Spectrum (500 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 0.84 (mt: 2H); 0.98 (t, J = 7 Hz: 3H); 1.00 to 2.65 (mt: 25H); 3.02 (mt: 2H); 3.93 (s: 3 H); 3.95 (q, J = 7 Hz: 2H); 7.31 (broad s: 1H); 7.35 (broad d, J = 9 Hz: 1H); 7.94 (d, J = 9 Hz: 1H); 8.67 (broad s: 1H).
    [3792] Ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate was prepared in Example 11.
    [3793] Example 33
    [3794] 1- (2-cyclohexylthioethyl) -4- [3- (3-fluoro-6-methoxy-quinolin-4-yl) propyl] piperidine-4-carboxylic acid
    [3795] Ethyl 1- (2-cyclohexylthioethyl) -4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl in 3 cm 3 dioxane, 3 cm 3 methanol and 1.7 cm 3 5N sodium hydroxide aqueous solution ] The mixture with 0.3 g of piperidine-4-carboxylate was stirred at 70 ° C. for 17 hours. After cooling to about 20 ° C., the reaction mixture was concentrated to dryness under pressure gradually decreasing from 30 kPa to 2.5 kPa at 45 ° C. temperature. The residue was dissolved in 5 cm 3 of dichloromethane / methanol / aqueous ammonia (40/5 / 0.5 volume ratio) and then eluted with a dichloromethane / methanol / aqueous ammonia (40/5 / 0.5 volume ratio) mixture, followed by chloroform / methanol / Purification was performed by chromatography on a silica gel cartridge (Bond Elut; particle size 70-200μ; mass 10 g) eluting with an aqueous ammonia mixture (13/3 / 0.5). The fractions containing the product were combined, concentrated to dryness under reduced pressure (2 kPa) at 40 ° C. and then dried in a drier (10 kPa). 0.25 g of 1- (2-cyclohexylthioethyl) -4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylic acid was obtained in the form of a white solid. .
    [3796] 1 H NMR spectrum (400 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm) added a few drops of CF 3 COOD): 1.15 to 1.35 (mt: 5H); 1.50 to 1.75 (mt: 8H); 1.80 to 2.05 (mt: 3H); 2.20 (broad d, J = 14 Hz: 2H); 2.65 to 2.90 (mt: 5H); 3.20 (broad t, J = 7Hz: 2H); 3.25 (mt: 2 H); 3.50 (broad d, J = 12 Hz: 2H); 4.00 (s: 3 H); 7.50 (d, J = 2.5 Hz: 1H); 7.59 (dd, J = 9 and 2.5 Hz: 1H); 8.09 (d, J = 9 Hz: 1 H); 9.07 (d, J = 2.5 Hz: 1H).
    [3797] Ethyl 1- (2-cyclohexylthioethyl) -4- [3- (3-fluoro-6-methoxy-quinolin-4-yl) propyl] piperidine-4-carboxylate
    [3798] 0.4 g of ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate, 0.23 g of 2-chloroethylthiocyclohexane, 0.18 g of potassium iodide, and A mixture of 0.74 g of potassium carbonate and 15 cm 3 of acetonitrile was stirred at 70 ° C. for 18 hours. After cooling to about 20 ° C., the reaction mixture was concentrated to dryness at 40 ° C. under reduced pressure (5 kPa). The resulting evaporated residue was purified by chromatography under atmospheric pressure on a silica gel cartridge (Bond Elut; particle size 70 to 200 μ; mass 12 g) eluted with a mixture of ethyl acetate / 40 to 60 ° C. petroleum ether (8/2 volume ratio). Fractions containing product were combined and concentrated to dryness at 40 ° C. under reduced pressure (2 kPa). 0.32 g of ethyl 1- (2-cyclohexylthioethyl) -4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate were obtained.
    [3799] 1 H NMR spectrum (500 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 0.97 (t, J = 7 Hz: 3H); 1.05 to 1.70 (mt: 14 H); 1.75 to 2.00 (mt: 6H); 2.25 to 2.60 (mt: 6H); 2.62 (mt: 1 H); 3.01 (mt: 2H); 3.91 (s: 3 H); 3.94 (q, J = 7 Hz: 2H); 7.30 (broad s: 1H); 7.37 (broad d, J = 9 Hz: 1H); 7.93 (d, J = 9 Hz: 1 H); 8.66 (broad s: 1H).
    [3800] Ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate was prepared in Example 11.
    [3801] Example 34
    [3802] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl) piperidine-4-carboxylic acid
    [3803] Ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl)-in 3 cm3 of dioxane, 3 cm3 of methanol and 0.6 cm3 of 5N aqueous sodium hydroxide solution A mixture of 0.1 g of piperidine-4-carboxylate was stirred at 70 ° C. for 17 hours. After cooling to about 20 ° C., the reaction mixture was evaporated at 45 ° C. under pressure gradually decreasing from 30 kPa to 2.5 kPa. The residue was dissolved in 5 cm 3 of dichloromethane / methanol / aqueous ammonia (40/5 / 0.5 volume ratio) and then eluted with a dichloromethane / methanol / aqueous ammonia (40/5 / 0.5 volume ratio) mixture, followed by chloroform / methanol / Purification was performed by chromatography on a silica gel cartridge (Bond Elut; particle size 70-200μ; mass 10 g) eluting with an aqueous ammonia mixture (13/3 / 0.5). The fractions containing the product were combined, concentrated to dryness under reduced pressure (2 kPa) at 40 ° C. and then dried in a drier (10 kPa). 0.25 g of 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl) -piperidine-4-carboxylic acid was obtained in the form of a white solid.
    [3804] 1 H NMR spectrum (400 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm) added a few drops of CF 3 COOD): 1.50 to 1.75 (mt: 6H); 1.85 to 2.05 (mt: 2H); 2.19 (broad d, J = 14 Hz: 2H); 2.60 (t, J = 7.5 Hz: 2H); 2.81 (broad t, J = 12.5 Hz: 2H); 3.07 (mt: 2 H); 3.20 (broad t, J = 7.5 Hz: 2H); 3.47 (broad d, J = 12.5 Hz: 2H); 3.99 (s: 3 H); 7.15 to 7.35 (mt: 5H); 7.51 (d, J = 2.5 Hz: 1H); 7.59 (dd, J = 9 and 2.5 Hz: 1H); 8.10 (d, J = 9 Hz: 1H); 9.08 (d, J = 2 Hz: 1H).
    [3805] Ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl) piperidine-4-carboxylate
    [3806] 0.4 g of ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate, 0.25 g of 1-bromo-3-phenylpropane, 0.181 of potassium iodide g and 0.74 g of potassium carbonate were mixed with 15 cm 3 of acetonitrile and stirred at 70 ° C. for 18 hours. After cooling to about 20 ° C., the reaction mixture was concentrated to dryness at 40 ° C. under reduced pressure (5 kPa). The evaporated residue was purified by chromatography under atmospheric pressure on a silica gel cartridge (Bond Elut; particle size 70-200 μ; mass 12 g) eluted with a mixture of ethyl acetate / 40-60 ° C. petroleum ether (8/2 vol. Ratio). Fractions containing product were combined and concentrated to dryness at 40 ° C. under reduced pressure (2 kPa). 0.1 g of ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl) piperidine-4-carboxylate were obtained.
    [3807] 1 H NMR spectrum (500 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 0.97 (t, J = 7 Hz: 3H); 1.25 to 2.00 (mt: 12H); 2.25 to 2.70 (mt: 6H); 3.01 (mt: 2H); 3.91 (s: 3 H); 3.94 (broad q, J = 7 Hz: 2H); 7.15 (mt: 3 H); 7.24 (broad t, J = 7.5 Hz: 2H); 7.30 (broad s: 1H); 7.36 (broad d, J = 9 Hz: 1H); 7.93 (d, J = 9 Hz: 1 H); 8.66 (broad s: 1H).
    [3808] Ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate was prepared in Example 11.
    [3809] Example 35
    [3810] 1- [2- (2,5-difluorophenylthio) ethyl] -4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylic acid
    [3811] Ethyl 1- [2- (2,5-difluorophenylthio) ethyl] -4- [3- (3-fluoro-6-meth) in 3 cm 3 of dioxane, 3 cm 3 in methanol and 1.4 cm 3 in 5N aqueous sodium hydroxide solution A mixture of 0.26 g of oxyquinolin-4-yl) propyl] piperidine-4-carboxylate was stirred at 70 ° C. for 17 hours. After cooling to about 20 ° C., the reaction mixture was evaporated at 45 ° C. under pressure gradually decreasing from 30 kPa to 2.5 kPa. The residue was dissolved in 5 cm 3 of dichloromethane / methanol / aqueous ammonia (40/5 / 0.5 volume ratio) and then eluted with a mixture of dichloromethane / methanol / aqueous ammonia (90/9 / 0.9 volume ratio), followed by chloroform / methanol / Purification was carried out by chromatography on a silica gel cartridge (Bond Elut; particle size 70-200μ; mass 10 g) eluting with an aqueous ammonia mixture (77.5 / 19.5 / 3). The fractions containing the product were combined, concentrated to dryness under reduced pressure (2 kPa) at 40 ° C. and then dried in a drier (10 kPa). 1- [2- (2,5-difluorophenylthio) ethyl] -4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylic acid 0.3 g was obtained in the form of a white solid.
    [3812] 1 H NMR spectrum (400 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm) added a few drops of CF 3 COOD): 1.50 to 1.75 (mt: 6H); 2.21 (broad d, J = 14 Hz: 2H); 2.89 (broad t, J = 12.5 Hz: 2H); 3.16 (mt: 2 H); 3.25 to 3.50 (mt: 4H); 3.54 (broad d, J = 12.5 Hz: 2H); 3.99 (s: 3 H); 7.14 (mt: 1 H); 7.30 (heterogeneous triplet, J = 9 and 5 Hz: 1H); 7.39 (mt: 1 H); 7.47 (d, J = 2.5 Hz: 1 H); 7.54 (dd, J = 9 and 2.5 Hz: 1H); 8.07 (d, J = 9 Hz: 1H); 8.97 (d, J = 2 Hz: 1H).
    [3813] Ethyl 1- [2- (2,5-difluorophenylthio) ethyl] -4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxyl Rate
    [3814] 0.4 g of ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate, 2- (2-bromoethylthio) -1,4- A mixture of 0.324 g of difluorobenzene, 0.181 g of potassium iodide, and 0.74 g of potassium carbonate was mixed in 15 cm 3 of acetonitrile was stirred at 70 ° C. for 18 hours. After cooling to about 20 ° C., the reaction mixture was concentrated to dryness at 40 ° C. under reduced pressure (5 kPa). The resulting evaporated residue was purified by chromatography under atmospheric pressure on a silica gel cartridge (Bond Elut; particle size 70 to 200 μ; mass 12 g) eluted with a mixture of ethyl acetate / 40 to 60 ° C. petroleum ether (8/2 by volume). Fractions containing product were combined and concentrated to dryness at 40 ° C. under reduced pressure (2 kPa). Ethyl 1- [2- (2.5-difluorophenylthio) ethyl] -4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate 0.27 g was obtained.
    [3815] 1 H NMR spectrum (500 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 0.97 (t, J = 7 Hz: 3H); 1.31 (broad t, J = 11 Hz: 2H); 1.40 to 1.60 (mt: 4H); 1.80 to 2.00 (mt: 4H); 2.35 to 2.70 (mt: 4H); 3.01 (mt: 2H); 3.07 (broad t, J = 7Hz: 2H); 3.91 (s: 3 H); 3.94 (q, J = 7 Hz: 2H); 7.00 (mt: 1 H); 7.21 (mt: 1 H); 7.26 (mt: 1 H); 7.30 (broad s: 1H); 7.37 (broad d, J = 9 Hz: 1H); 7.93 (d, J = 9 Hz: 1 H); 8.66 (broad s: 1H).
    [3816] Ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate was prepared in Example 11.
    [3817] 1- (2-bromoethylthio) -2,5-difluorobenzene was prepared in Example 14.
    [3818] Example 36
    [3819] 1- [2- (2,5-difluorophenoxy) ethyl] -4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylic acid
    [3820] Ethyl 1- [2- (2,5-difluorophenoxy) ethyl] -4- [3- (3-fluoro-6-meth) in 3 cm 3 of dioxane, 3 cm 3 in methanol and 2.1 cm 3 in 5N aqueous sodium hydroxide solution A mixture of 0.38 g of oxyquinolin-4-yl) propyl] piperidine-4-carboxylate was stirred at 70 ° C. for 17 hours. After cooling to about 20 ° C., the reaction mixture was concentrated to dryness under pressure gradually decreasing from 30 kPa to 2.5 kPa at 45 ° C. temperature. The residue was dissolved in 5 cm 3 of dichloromethane / methanol / aqueous ammonia (40/5 / 0.5 volume ratio) and then eluted with a mixture of dichloromethane / methanol / aqueous ammonia (90/9 / 0.9 volume ratio), followed by chloroform / methanol / Purification was carried out by chromatography on a silica gel cartridge (Bond Elut; particle size 70-200μ; mass 10 g) eluting with an aqueous ammonia mixture (77.5 / 19.5 / 3). The fractions containing the product were combined, concentrated to dryness under reduced pressure (2 kPa) at 40 ° C. and then dried in a drier (10 kPa). 1- [2- (2,5-difluorophenoxy) ethyl] -4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylic acid 0.36 g was obtained in the form of a white solid.
    [3821] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.32 (broad t, J = 13 Hz: 2H); 1.50 to 1.70 (mt: 4H); 1.96 (broad d, J = 13 Hz: 2H); 2.09 (broad t, J = 11.5 Hz: 2H); 2.64 (t, J = 6 Hz: 2H); 2.70 (broad d, J = 11.5 Hz: 2H); 3.05 (very broad t, J = 6.5 Hz: 2H); 3.96 (s: 3 H); 4.13 (t, J = 6 Hz: 2H); 6.75 (mt: 1 H); 7.14 (mt: 1 H); 7.24 (mt: 1 H); 7.34 (d, J = 2.5 Hz: 1 H); 7.41 (dd, J = 9 and 2.5 Hz: 1H); 7.97 (d, J = 9 Hz: 1 H); 8.69 (broad s: 1H).
    [3822] Ethyl 1- [2- (2,5-difluorophenoxy) ethyl] -4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxyl Rate
    [3823] 0.4 g of ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate, 2- (2-bromoethoxy) -1,4-di A mixture of 0.30 g of fluorobenzene, 0.181 g of potassium iodide and 0.74 g of potassium carbonate was mixed in 15 cm 3 of acetonitrile, and stirred at 70 ° C. for 18 hours. After cooling to about 20 ° C., the reaction mixture was concentrated to dryness at 40 ° C. under reduced pressure (5 kPa). The resulting evaporated residue was purified by chromatography under atmospheric pressure on a silica gel cartridge (Bond Elut; particle size 70 to 200 μ; mass 12 g) eluted with a mixture of ethyl acetate / 40 to 60 ° C. petroleum ether (8/2 by volume). Fractions containing product were combined and concentrated to dryness at 40 ° C. under reduced pressure (2 kPa). Ethyl 1- [2- (2.5-difluorophenoxy) ethyl] -4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate 0.4 g was obtained.
    [3824] 1 H NMR spectrum (500 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 0.97 (t, J = 7 Hz: 3H); 1.36 (broad t, J = 11.5 Hz: 2H); 1.40 to 1.60 (mt: 4H); 1.80 to 2.10 (mt: 4H); 2.61 (broad t, J = 5.5 Hz: 2H); 2.69 (broad d, J = 11 Hz: 2H); 3.02 (mt: 2H); 3.92 (s: 3 H); 3.94 (q, J = 7 Hz: 2H); 4.09 (mt: 2 H); 6.71 (mt: 1 H); 7.10 (mt: 1 H); 7.19 (mt: 1 H); 7.29 (broad s: 1H); 7.37 (broad d, J = 9 Hz: 1H); 7.93 (d, J = 9 Hz: 1 H); 8.66 (broad s: 1H).
    [3825] Ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate was prepared in Example 11.
    [3826] 2- (2-bromoethoxy) -1,4-difluorobenzene was prepared in Example 16.
    [3827] Example 37
    [3828] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy) ethyl] piperidine-4- Carboxylic acid
    [3829] Ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3 in 3 cm 3 dioxane, 3 cm 3 methanol and 2.3 cm 3 5N aqueous sodium hydroxide solution A mixture of 0.42 g of, 5-trifluorophenoxy) ethyl] piperidine-4-carboxylate was stirred at 70 ° C. for 17 hours. After cooling to about 20 ° C., the reaction mixture was concentrated to dryness at a pressure gradually decreasing from 30 kPa to 2.5 kPa at 45 ° C. temperature. The residue was dissolved in 5 cm 3 of dichloromethane / methanol / aqueous ammonia (40/5 / 0.5 volume ratio) and then eluted with a mixture of dichloromethane / methanol / aqueous ammonia (90/9 / 0.9 volume ratio), followed by chloroform / methanol / Purification was carried out by chromatography on a silica gel cartridge (Bond Elut; particle size 70-200μ; mass 10 g) eluting with an aqueous ammonia mixture (77.5 / 19.5 / 3). The fractions containing the product were combined, concentrated to dryness under reduced pressure (2 kPa) at 40 ° C. and then dried in a drier (10 kPa). 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy) ethyl] piperidine-4- 0.39 g of carboxylic acid was obtained in the form of a white solid.
    [3830] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.32 (very broad t, J = 12.5 Hz: 2H); 1.60 (mt: 4H); 1.95 (broad d, J = 12.5 Hz: 2H); 2.09 (broad t, J = 11 Hz: 2H); 2.64 (t, J = 5.5 Hz: 2H); 2.70 (broad d, J = 11 Hz: 2H); 3.04 (very broad t, J = 6 Hz: 2H); 3.96 (s: 3 H); 4.16 (t, J = 5.5 Hz: 2H); 6.95 to 7.15 (mt: 2H); 7.34 (d, J = 2.5 Hz: 1 H); 7.40 (dd, J = 9 and 2.5 Hz: 1H); 7.96 (d, J = 9 Hz: 1H); 8.69 (broad s: 1H).
    [3831] Ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy) ethyl] piperidine-4 Carboxylate
    [3832] 0.4 g of ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate, 1- (2-bromoethoxy) -2,3,5 A mixture of 0.33 g of -trifluorobenzene, 0.181 g of potassium iodide and 0.74 g of potassium carbonate was mixed with 15 cm 3 of acetonitrile was stirred at a temperature of 70 ° C. for 18 hours. After cooling to about 20 ° C., the reaction mixture was concentrated to dryness at 40 ° C. under reduced pressure (5 kPa). The resulting evaporated residue was purified by chromatography under atmospheric pressure on a silica gel cartridge (Bond Elut; particle size 70 to 200 μ; mass 12 g; volume 25 cm 3) eluted with an ethyl acetate / 40 to 60 ° C. petroleum ether (8/2 volume ratio) mixture. It was. Fractions containing product were combined and concentrated to dryness at 40 ° C. under reduced pressure (2 kPa). Ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,3,5-trifluorophenoxy) ethyl] piperidine-4 0.43 g of carboxylate was obtained.
    [3833] 1 H NMR spectrum (500 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 0.98 (t, J = 7 Hz: 3H); 1.34 (broad t, J = 11.5 Hz: 2H); 1.45 to 1.60 (mt: 4H); 1.85 to 2.10 (mt: 4H); 2.50 to 2.70 (mt: 4H); 3.02 (mt: 2H); 3.92 (s: 3 H); 3.94 (q, J = 7 Hz: 2H); 4.14 (mt: 2 H); 7.02 (mt: 2H); 7.30 (broad s: 1H); 7.37 (broad d, J = 9 Hz: 1H); 7.94 (d, J = 9 Hz: 1H); 8.66 (broad s: 1H).
    [3834] Ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate was prepared in Example 11.
    [3835] 1- (2-bromoethoxy) -2,3,5-trifluorobenzene was prepared as described in Example 13.
    [3836] Example 38
    [3837] 4- [3- (3-Fluoro-6-methoxyquinolin-4-yl) propyl] -1-heptylpiperidine-4-carboxylic acid
    [3838] Ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1-heptylpiperidine-4- in 3 cm 3 of dioxane, 3 cm 3 in methanol and 1 cm 3 in 5N sodium hydroxide aqueous solution A mixture of 0.16 g of carboxylate was stirred at 70 ° C. for 17 hours. After cooling to about 20 ° C., the reaction mixture was concentrated to dryness under pressure gradually decreasing from 30 kPa to 2.5 kPa at 45 ° C. temperature. The residue was dissolved in 5 cm 3 of a mixture of dichloromethane / methanol / aqueous ammonia (40/5 / 0.5 volume ratio), and then eluted with a mixture of dichloromethane / methanol / aqueous ammonia (40/5 / 0.5 volume ratio), followed by chloroform Purification was carried out by chromatography on a silica gel cartridge (Bond Elut; particle size 70-200μ; mass 10 g) eluting with a / methanol / aqueous ammonia mixture (13/3 / 0.5). The fractions containing the product were combined, concentrated to dryness under reduced pressure (2 kPa) at 40 ° C. and then dried in a drier (10 kPa). 0.07 g of 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1-heptylpiperidine-4-carboxylic acid was obtained in the form of a white solid.
    [3839] 1 H NMR spectrum (400 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm) added a few drops of CF 3 COOD): 0.85 (t, J = 7 Hz: 3H); 1.15 to 1.35 (mt: 8H); 1.50 to 1.75 (mt: 8H); 2.19 (broad d, J = 14 Hz: 2H); 2.78 (broad t, J = 12.5 Hz: 2H); 3.02 (mt: 2H); 3.19 (broad t, J = 7Hz: 2H); 3.45 (broad d, J = 12.5 Hz: 2H); 4.00 (s: 3 H); 7.50 (d, J = 2.5 Hz: 1H); 7.58 (dd, J = 9 and 2.5 Hz: 1H); 8.09 (d, J = 9 Hz: 1H); 9.04 (d, J = 2 Hz: 1H).
    [3840] Ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1-heptylpiperidine-4-carboxylate
    [3841] 0.4 g of ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate, 0.23 g of 1-bromoheptane, 0.18 g of potassium iodide and potassium carbonate A mixture of 0.737 g of 15 cm 3 of acetonitrile was stirred at 70 ° C. for 18 hours. After cooling to about 20 ° C., the reaction mixture was concentrated to dryness at 40 ° C. under reduced pressure (5 kPa). The evaporated residue obtained was purified by chromatography under atmospheric pressure on a silica gel cartridge (particle size 70-200 μ; mass 12 g) eluted with a mixture of ethyl acetate / 40-60 ° C. petroleum ether (8/2 volume ratio). Fractions containing product were combined and concentrated to dryness at 40 ° C. under reduced pressure (2 kPa). 0.2 g of ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1-heptylpiperidine-4-carboxylate were obtained.
    [3842] 1 H NMR spectrum (500 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 0.84 (t, J = 7 Hz: 3H); 0.98 (t, J = 7 Hz: 3H); 1.10-1.30 (mt: 8H); 1.33 (mt: 4H); 1.40 to 1.60 (mt: 4H); 1.83 (broad t, J = 11 Hz: 2H); 1.93 (broad d, J = 13 Hz: 2H); 2.13 (mt: 2 H); 2.35 to 2.55 (mt: 2H); 3.01 (mt: 2H); 3.89 (s: 3 H); 3.94 (mt: 2 H); 7.31 (broad s: 1H); 7.37 (broad d, J = 9 Hz: 1H); 7.94 (d, J = 9 Hz: 1H); 8.67 (broad s: 1H).
    [3843] Ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate was prepared in Example 11.
    [3844] Example 39
    [3845] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- (2-phenylthioethyl) piperidine-4-carboxylic acid
    [3846] Dioxane 3cm 3, 3cm 3 of methanol and 5N sodium hydroxide solution was 2.3cm 3 of ethyl 4- [3- (3-fluoro-6-methoxy-quinolin-4-yl) propyl] -1- (2-phenylthio ethyl A mixture of 0.39 g of piperidine-4-carboxylate was stirred at a temperature of 70 ° C. for 17 hours. After cooling to about 20 ° C., the reaction mixture was concentrated to dryness at a temperature of 45 ° C. while slowly decreasing the pressure from 30 kPa to 2.5 kPa. The residue was placed in a 5 cm 3 dichloromethane / methanol / aqueous ammonia mixture (40/5 / 0.5 by volume) and dichloromethane / methanol in a cartridge of silica gel (Bond Elut; particle size 70-200 μ; mass 10 g) under atmospheric pressure. Purification by chromatography eluting with an aqueous ammonia mixture (90/9 / 0.9 by volume) followed by a dichloroform / methanol / aqueous ammonia mixture (77.5 / 19.5 / 3). Fractions containing product were combined, concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. and then dried in a dryer (10 kPa). 0.3 g of 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- (2-phenylthioethyl) piperidine-4-carboxylic acid in the form of a white solid It was.
    [3847] 1 H NMR spectrum (400 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm) added a few drops of CF 3 COOD): 1.50 to 1.75 (mt: 6H); 2.20 (broad d, J = 14 Hz: 2H); 2.87 (broad t, J = 13 Hz: 2H); 3.16 (mt: 2 H); 3.41 (s: 4 H); 3.53 (broad d, J = 13 Hz: 2H); 4.00 (s: 3 H); 7.25 (broad t, J = 7.5 Hz: 1H); 7.30 to 7.45 (mt: 4H); 7.48 (d, J = 2.5 Hz: 1H); 7.54 (dd, J = 9 and 2.5 Hz: 1H); 8.07 (d, J = 9 Hz: 1H); 8.97 (d, J = 2 Hz: 1H).
    [3848] Ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- (2-phenylthioethyl) piperidine-4-carboxylate
    [3849] 0.4 g of ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate in acetonitrile 15 cm 3 , 0.28 g of 2-bromoethyl phenyl sulfide, A mixture of 0.181 g of potassium iodide and 0.74 g of potassium carbonate was stirred at a temperature of 70 ° C. for 18 hours. After cooling to about 20 ° C., the reaction mixture was concentrated to dryness at a temperature of 40 ° C. under reduced pressure (5 kPa). The evaporated residue was purified by chromatography, eluting with a mixture of ethyl acetate / 40-60 ° C. petroleum ether (8/2 by volume) in a cartridge of silica gel (Bond Elut; particle size 70-200 μ; mass 12 g) under atmospheric pressure It was. Fractions containing product were combined and concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. 0.4 g of ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- (2-phenylthioethyl) piperidine-4-carboxylate were obtained.
    [3850] 1 H NMR spectrum (500 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 0.97 (t, J = 7 Hz: 3H); 1.33 (broad t, J = 12.5 Hz: 2H); 1.45 to 1.65 (mt: 4H); 1.85 to 2.00 (mt: 4H); 2.30 to 2.70 (mt: 4H); 3.01 (mt: 4H); 3.92 (s: 3 H); 3.94 (mt: 2 H); 7.15 (mt: 1 H); 7.20 to 7.35 (mt: 5H); 7.37 (broad d, J = 9 Hz: 1H); 7.93 (d, J = 9 Hz: 1 H); 8.66 (broad s: 1H).
    [3851] Ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate was prepared in Example 11.
    [3852] Example 40
    [3853] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3-fluorophenylthio) ethyl] piperidine-4-carboxylic acid
    [3854] Ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- (2-phenylthioethyl in dioxane 3 cm 3 , methanol 3 cm 3 and 5 N sodium hydroxide solution 1.1 cm 3 A mixture of 0.2 g of piperidine-4-carboxylate was stirred at a temperature of 70 ° C. for 17 hours. After cooling to about 20 ° C., the reaction mixture was concentrated to dryness at a temperature of 45 ° C. while slowly decreasing the pressure from 30 kPa to 2.5 kPa. The residue was placed in a 5 cm 3 dichloromethane / methanol / aqueous ammonia mixture (40/5 / 0.5 by volume) and dichloromethane / methanol / methanol in a cartridge of silica gel (BondElut; particle size 70-200 μ; mass 10 g) under atmospheric pressure. Purification was carried out by chromatography, eluting with an aqueous ammonia mixture (90/9 / 0.9 on a volume basis) followed by a chloroform / methanol / aqueous ammonia mixture (77.5 / 19.5 / 3). Fractions containing product were combined, concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. and then dried in a dryer (10 kPa). 0.18 g of 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3-fluorophenylthio) ethyl] piperidine-4-carboxylic acid Obtained.
    [3855] 1 H NMR spectrum (400 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm) added a few drops of CF 3 COOD): 1.50 to 1.75 (mt: 6H); 2.20 (broad d, J = 14 Hz: 2H); 2.89 (broad t, J = 12.5 Hz: 2H); 3.18 (mt: 2 H); 3.25 to 3.45 (mt: 4H); 3.54 (broad d, J = 12.5 Hz: 2H); 3.99 (s: 3 H); 7.05 (heterogeneous triplet, J = 9 and 2.5 Hz: 1H); 7.15 to 7.30 (mt: 2H); 7.38 (mt: 1 H); 7.48 (d, J = 2.5 Hz: 1H); 7.55 (dd, J = 9 and 2.5 Hz: 1H); 8.08 (d, J = 9 Hz: 1 H); 9.00 (d, J = 2 Hz: 1H).
    [3856] Ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- (2-phenylthioethyl) piperidine-4-carboxylate
    [3857] 0.4 g of ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate in acetonitrile 15 cm 3 , 3-fluoro-2-bromoethyl A mixture of 0.30 g of phenyl sulfide, 0.18 g of potassium iodide and 0.74 g of potassium carbonate was stirred at a temperature of 70 ° C. for 18 hours. After cooling to about 20 ° C., the reaction mixture was concentrated to dryness at a temperature of 40 ° C. under reduced pressure (5 kPa). The evaporated residue was purified by chromatography, eluting with a mixture of ethyl acetate / 40-60 ° C. petroleum ether (8/2 by volume) in a cartridge of silica gel (Bond Elut; particle size 70-200 μ; mass 12 g) under atmospheric pressure It was. Fractions containing product were combined and concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. 0.22 g of ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- (2-phenylthioethyl) piperidine-4-carboxylate were obtained.
    [3858] 1 H NMR spectrum (500 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 0.98 (t, J = 7 Hz: 3H); 1.33 (broad t, J = 12 Hz: 2H); 1.45 to 1.65 (mt: 4H); 1.85 to 2.00 (mt: 4H); 2.30 to 2.70 (mt: 4H); 3.02 (mt: 2H); 3.07 (t, J = 6.5 Hz: 2H); 3.92 (s: 3 H); 3.94 (q, J = 7 Hz: 2H); 6.94 (broad t, J = 8.5 Hz: 1H); 7.05 to 7.20 (mt: 2H); 7.25 to 7.35 (mt: 2H); 7.37 (broad d, J = 9 Hz: 1H); 7.94 (d, J = 9 Hz: 1H); 8.66 (broad s: 1H).
    [3859] Ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate was prepared in Example 11.
    [3860] 3-fluoro-2-bromoethyl phenyl sulfide was prepared according to the method described in Example 14.
    [3861] Example 41
    [3862] 1- [2- (3,4-difluorophenoxy) ethyl] -4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylic acid
    [3863] Ethyl 1- [2- (3,4-difluorophenoxy) ethyl] -4- (3-fluoro-6-methoxyquinoline in dioxane 3 cm 3 , methanol 3 cm 3 and 5 N sodium hydroxide solution 2.1 cm 3 A mixture of 0.38 g of -4-yl) propyl] piperidine-4-carboxylate was stirred at a temperature of 70 ° C. for 17 hours. After cooling to about 20 ° C., the reaction mixture was concentrated to dryness at a temperature of 45 ° C. while slowly decreasing the pressure from 30 kPa to 2.5 kPa. The residue was placed in a 5 cm 3 dichloromethane / methanol / aqueous ammonia mixture (40/5 / 0.5 by volume) and dichloromethane / methanol in a cartridge of silica gel (Bond Elut; particle size 70-200 μ; mass 10 g) under atmospheric pressure. Purification by chromatography, eluting with an aqueous ammonia mixture (90/9 / 0.9 on a volume basis) followed by a chloroform / methanol / aqueous ammonia mixture (77.5 / 19.5 / 3). Fractions containing product were combined, concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. and then dried in a dryer (10 kPa). 0.3 g 1- [2- (3,4-difluorophenoxy) ethyl] -4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4 -Carboxylic acid was obtained in the form of a white solid.
    [3864] 1 H NMR spectrum (400 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm) added a few drops of CF 3 COOD): 1.50 to 1.75 (mt: 6H); 2.21 (broad d, J = 14 Hz: 2H); 2.96 (broad t, J = 13 Hz: 2H); 3.19 (broad t, J = 6.5 Hz: 2H); 3.50 to 3.65 (mt: 4H); 4.00 (s: 3 H); 4.31 (t, J = 5.5 Hz: 2H); 6.82 (mt: 1 H); 7.11 (mt: 1 H); 7.35 (mt: 1 H); 7.50 (d, J = 2.5 Hz: 1H); 7.57 (dd, J = 9 and 2.5 Hz: 1H); 8.09 (d, J = 9 Hz: 1 H); 9.03 (d, J = 2 Hz: 1H).
    [3865] Ethyl 1- [2- (3,4-difluorophenoxy) ethyl] -4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxyl Rate
    [3866] 0.4 g of ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate in acetonitrile 15 cm 3 , 4- (2-bromoethoxy)- A mixture of 0.3 g of 1,2-difluorobenzene, 0.18 g of potassium iodide and 0.74 g of potassium carbonate was stirred at a temperature of 70 ° C. for 18 hours. After cooling to about 20 ° C., the reaction mixture was concentrated to dryness at a temperature of 40 ° C. under reduced pressure (5 kPa). The evaporated residue was purified by chromatography, eluting with a mixture of ethyl acetate / 40-60 ° C. petroleum ether (8/2 by volume) in a cartridge of silica gel (Bond Elut; particle size 70-200 μ; mass 12 g) under atmospheric pressure It was. Fractions containing product were combined and concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. 0.4 g of ethyl 1- [2- (3,4-difluorophenoxy) ethyl] -4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine- 4-carboxylate was obtained.
    [3867] 1 H NMR spectrum (500 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 0.98 (t, J = 7 Hz: 3H); 1.36 (broad t, J = 12 Hz: 2H); 1.45 to 1.65 (mt: 4H); 1.93 (broad d, J = 12 Hz: 2H); 2.00 (broad t, J = 11.5 Hz: 2H); 2.40 to 2.70 (mt: 4H); 3.02 (mt: 2H); 3.92 (s: 3 H); 3.94 (q, J = 7 Hz: 2H); 3.99 (mt: 2 H); 6.73 (mt: 1 H); 7.03 (mt: 1 H); 7.25 to 7.35 (mt: 2H); 7.37 (broad d, J = 9 Hz: 1H); 7.93 (d, J = 9 Hz: 1 H); 8.66 (broad s,: 1H).
    [3868] 4- (2-bromoethoxy) -1,2-difluorobenzene
    [3869] A mixture of 15 g of 3,4-difluorophenol, 23.5 g of potassium carbonate and 60 cm 3 of 1,2-dibromoethane in acetonitrile 250 cm 3 was stirred at a temperature of 70 ° C. for 18 hours. After cooling to about 20 ° C, the reaction mixture was filtered through celite and concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. The obtained residue was purified by chromatography eluting with a mixture of 40-60 ° C. petroleum ether on a column of silica gel (particle size 70-200 μ; diameter 8 cm; mass 400 g) under atmospheric pressure. Fractions containing product were combined and concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. 15.7 g of 4- (2-bromoethoxy) -1,2-difluorobenzene were obtained in the form of an oil.
    [3870] Infrared spectrum (CCl 4 ): 1609; 1516; 1264; 1253; 1215; 1206; 1162; 1019; 854 and 834 cm -1 .
    [3871] Ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate was prepared in Example 11.
    [3872] Example 42
    [3873] 4- [3- (3-Fluoro-6-methoxyquinolin-4-yl) propyl] -1- (2-phenoxyethyl) piperidine-4-carboxylic acid
    [3874] Ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- (2-phenoxyethyl in dioxane 3 cm 3 , methanol 3 cm 3 and 5 N aqueous sodium hydroxide solution 2.4 cm 3 A mixture of 0.39 g of piperidine-4-carboxylate was stirred at a temperature of 70 ° C. for 17 hours. After cooling to about 20 ° C., the reaction mixture was concentrated to dryness at a temperature of 45 ° C. while slowly decreasing the pressure from 30 kPa to 2.5 kPa. The residue was placed in a 5 cm 3 dichloromethane / methanol / aqueous ammonia mixture (40/5 / 0.5 by volume) and dichloromethane / methanol in a cartridge of silica gel (Bond Elut; particle size 70-200 μ; mass 10 g) under atmospheric pressure. Purification by chromatography, eluting with an aqueous ammonia mixture (90/9 / 0.9 on a volume basis) followed by a chloroform / methanol / aqueous ammonia mixture (77.5 / 19.5 / 3). Fractions containing product were combined, concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. and then dried in a dryer (10 kPa). 0.33 g of 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- (2-phenoxyethyl] piperidine-4-carboxylic acid in the form of a white solid It was.
    [3875] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm) added a few drops of CF 3 COOD): 1.36 (broad t, J = 12.5 Hz: 2H); 1.50 to 1.70 (mt: 4H); 1.96 (broad d, J = 12.5 Hz: 2H); 2.08 (broad t, J = 11.5 Hz: 2H); 2.62 (t, J = 6 Hz: 2H); 2.71 (broad d, J = 11.5 Hz: 2H); 3.05 (broad t, J = 6.5 Hz: 2H); 3.97 (s: 3 H); 4.03 (t, J = 6 Hz: 2H); 6.85 to 7.00 (mt: 3H); 7.29 (broad t, J = 8 Hz: 2H); 7.35 (d, J = 2.5 Hz: 1H); 7.40 (dd, J = 9 and 2.5 Hz: 1H); 7.97 (d, J = 9 Hz: 1 H); 8.70 (broad s: 1H).
    [3876] Ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- (2-phenoxyethyl) piperidine-4-carboxylate
    [3877] 0.4 g of ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate in acetonitrile 15 cm 3 , 0.26 g of 2-bromoethyl phenyl ether, A mixture of 0.181 g of potassium iodide and 0.737 g of potassium carbonate was stirred at a temperature of 70 ° C. for 18 hours. After cooling to about 20 ° C., the reaction mixture was concentrated to dryness at a temperature of 40 ° C. under reduced pressure (5 kPa). The evaporated residue was purified by chromatography, eluting with a mixture of ethyl acetate / 40-60 ° C. petroleum ether (8/2 by volume) in a cartridge of silica gel (Bond Elut; particle size 70-200 μ; mass 12 g) under atmospheric pressure It was. Fractions containing product were combined and concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. 0.4 g of ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- (2-phenoxyethyl) piperidine-4-carboxylate were obtained.
    [3878] 1 H NMR spectrum (500 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 0.99 (t, J = 7 Hz: 3H); 1.37 (mt: 2 H); 1.45 to 1.65 (mt: 4H); 1.85 to 2.10 (mt: 4H); 2.35 to 2.75 (mt: 4H); 3.03 (mt: 2 H); 3.93 (s: 3 H); 3.96 (q, J = 7 Hz: 2H); 4.02 (mt: 2 H); 6.90 (mt: 3 H); 7.26 (broad t, J = 7.5 Hz: 2H); 7.32 (broad s: 1H); 7.38 (broad d, J = 9 Hz: 1H); 7.95 (d, J = 9 Hz: 1H); 8.68 (broad s: 1H).
    [3879] Ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate was prepared in Example 11.
    [3880] Example 43
    [3881] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3-fluorophenoxy) ethyl] piperidine-4-carboxylic acid
    [3882] Ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3- in dioxane 3 cm 3 , methanol 3 cm 3 and 5 N aqueous sodium hydroxide solution 2.4 cm 3 A mixture of 0.415 g of fluorophenoxy) ethyl] piperidine-4-carboxylate was stirred at a temperature of 70 ° C. for 17 hours. After cooling to about 20 ° C., the reaction mixture was concentrated to dryness at a temperature of 45 ° C. while slowly decreasing the pressure from 30 kPa to 2.5 kPa. The residue was placed in a 5 cm 3 dichloromethane / methanol / aqueous ammonia mixture (40/5 / 0.5 by volume) and dichloromethane / methanol in a cartridge of silica gel (Bond Elut; particle size 70-200 μ; mass 10 g) under atmospheric pressure. Purification by chromatography, eluting with an aqueous ammonia mixture (90/9 / 0.9 on a volume basis) followed by a chloroform / methanol / aqueous ammonia mixture (77.5 / 19.5 / 3). Fractions containing the product were combined, concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. and then dried in a dryer (10 kPa). 0.34 g of 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3-fluorophenoxy) ethyl] piperidine-4-carboxylic acid Obtained in the form of a white solid.
    [3883] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 D, δ (ppm) with a few drops of CF 3 COOD): 1.34 (broad t, J = 12.5 Hz: 2H); 1.50 to 1.70 (mt: 4H); 1.96 (broad d, J = 12.5 Hz: 2H); 2.08 (broad t, J = 11 Hz: 2H); 2.63 (t, J = 6 Hz: 2H); 2.70 (broad d, J = 11 Hz: 2H); 3.05 (broad t, J = 6.5 Hz: 2H); 3.97 (s: 3 H); 4.06 (t, J = 6 Hz: 2H); 6.70 to 6.90 (mt: 3H); 7.25 to 7.40 (mt: 1 H); 7.35 (d, J = 2.5 Hz: 1H); 7.40 (dd, J = 9 and 2.5 Hz: 1H); 7.97 (d, J = 9 Hz: 1 H); 8.70 (broad s: 1H).
    [3884] Ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3-fluorophenoxy) ethyl] piperidine-4-carboxylate
    [3885] 0.4 g of ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate in acetonitrile 15 cm 3 , 1- (2-bromoethoxy)- A mixture of 0.281 g of 3-fluorobenzene, 0.181 g of potassium iodide and 0.737 g of potassium carbonate was stirred at a temperature of 70 ° C. for 18 hours. After cooling to about 20 ° C., the reaction mixture was concentrated to dryness at a temperature of 40 ° C. under reduced pressure (5 kPa). The evaporated residue was purified by chromatography, eluting with a mixture of ethyl acetate / 40-60 ° C. petroleum ether (8/2 by volume) in a cartridge of silica gel (Bond Elut; particle size 70-200 μ; mass 12 g) under atmospheric pressure It was. Fractions containing product were combined and concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. 0.43 g of ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3-fluorophenoxy) ethyl] piperidine-4-carboxyl The rate was obtained.
    [3886] 1 H NMR spectrum (500 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 0.98 (t, J = 7 Hz: 3H); 1.35 (broad t, J = 12 Hz: 2H); 1.45 to 1.65 (mt: 4H); 1.92 (broad d, J = 12 Hz: 2H); 2.00 (broad t, J = 11.5 Hz: 2H); 2.30 to 2.70 (mt: 4H); 3.02 (mt: 2H); 3.91 (s: 3 H); 3.94 (q, J = 7 Hz: 2H); 4.01 (mt: 2 H); 6.65 to 6.80 (mt: 3H); 7.20 to 7.30 (mt: 1 H); 7.28 (broad s: 1H); 7.36 (broad d, J = 9 Hz: 1H); 7.93 (d, J = 9 Hz: 1 H); 8.65 (broad s: 1H).
    [3887] 1- (2-bromoethoxy) -3-fluorobenzene
    [3888] A mixture of acetonitrile 200cm 3 3-fluoro-phenol 8.6g of potassium carbonate and 15.3g of 1,2-dibromoethane 40.5cm 3 at a temperature of 70 ℃, and stirred for 25 hours under an inert atmosphere. After cooling to about 20 ° C., the suspension was filtered, the insoluble material was washed three times with 50 cm 3 of acetonitrile and the filtrate was concentrated to dryness at 40 ° C. under reduced pressure (2 kPa). The obtained residue was taken in 50 cm 3 of diethyl ether and filtered, and the filtrate was concentrated to dryness as above conditions. The oil obtained by evaporation was purified by chromatography eluting with 40-60 ° C. petroleum ether on a column of silica gel (particle size 25-45 μ; diameter 4.5 cm; height 22 cm) under a pressure of argon 50 kPa. Fractions 8 to 60 were combined and then concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. 7.67 g of 1- (2-bromoethoxy) -3-fluorobenzene were obtained.
    [3889] Infrared spectrum (CCl 4 ): 1616; 1596; 1492; 1279; 1265; 1168; 1140; 1025; 853; 834 and 679 cm -1 .
    [3890] Ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate was prepared in Example 11.
    [3891] Example 44
    [3892] 1- [2- (2,6-difluorophenoxy) ethyl] -4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylic acid
    [3893] Ethyl 1- [2- (2,6-difluorophenoxy) ethyl] -4- [3- (3-fluoro-6- in dioxane 3 cm 3 , methanol 3 cm 3 and 5 N sodium hydroxide solution 2.2 cm 3 A mixture of 0.39 g of methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate was stirred at a temperature of 70 ° C. for 17 hours. After cooling to about 20 ° C., the reaction mixture was concentrated to dryness at a temperature of 45 ° C. while slowly decreasing the pressure from 30 kPa to 2.5 kPa. The residue was placed in a 5 cm 3 dichloromethane / methanol / aqueous ammonia mixture (40/5 / 0.5 by volume) and dichloromethane / methanol in a cartridge of silica gel (Bond Elut; particle size 70-200 μ; mass 10 g) under atmospheric pressure. Purification by chromatography, eluting with an aqueous ammonia mixture (90/9 / 0.9 on a volume basis) followed by a chloroform / methanol / aqueous ammonia mixture (77.5 / 19.5 / 3). Fractions containing product were combined, concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. and then dried in a dryer (10 kPa). 0.3 g 1- [2- (2,6-difluorophenoxy) ethyl] -4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4 -Carboxylic acid was obtained in the form of a white solid.
    [3894] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.33 (broad t, J = 12.5 Hz: 2H); 1.50 to 1.65 (mt: 4H); 1.91 (broad d, J = 12.5 Hz: 2H); 2.05 (broad t, J = 11 Hz: 2H); 2.60 (t, J = 6 Hz: 2H); 2.63 (mt: 2 H); 3.05 (mt: 2H); 3.97 (s: 3 H); 4.16 (t, J = 6 Hz: 2H); 7.05 to 7.20 (mt: 3H); 7.35 (d, J = 2.5 Hz: 1H); 7.40 (dd, J = 9 and 2.5 Hz: 1H); 7.97 (d, J = 9 Hz: 1 H); 8.70 (broad s: 1H).
    [3895] Ethyl 1- [2- (2,6-difluorophenoxy) ethyl] -4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxyl Rate
    [3896] 0.4 g of ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate in acetonitrile 15 cm 3 , 1- (2-bromoethoxy)- A mixture of 0.304 g of 3-fluorobenzene, 0.181 g of potassium iodide and 0.74 g of potassium carbonate was stirred at a temperature of 70 ° C. for 18 hours. After cooling to about 20 ° C., the reaction mixture was concentrated to dryness at a temperature of 40 ° C. under reduced pressure (5 kPa). The evaporated residue was purified by chromatography, eluting with a mixture of ethyl acetate / 40-60 ° C. petroleum ether (8/2 by volume) in a cartridge of silica gel (Bond Elut; particle size 70-200 μ; mass 12 g) under atmospheric pressure It was. Fractions containing product were combined and concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. 0.4 g of ethyl 1- [2- (2,6-difluorophenoxy) ethyl] -4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine- 4-carboxylate was obtained.
    [3897] 1 H NMR spectrum (500 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 0.97 (t, J = 7 Hz: 3H); 1.26 (broad t, J = 125 Hz: 2H); 1.40 to 1.60 (mt: 4H); 1.88 (broad d, J = 12 Hz: 2H); 1.98 (broad t, J = 11 Hz: 2H); 2.30 to 2.65 (mt: 4H); 3.00 (mt: 2 H); 3.92 (s: 3 H); 3.94 (mt: 2 H); 4.11 (mt: 2 H); 6.95 to 7.10 (mt: 3H); 7.30 (broad s: 1H); 7.37 (broad d, J = 9 Hz: 1H); 7.93 (d, J = 9 Hz: 1 H); 8.66 (broad s: 1H).
    [3898] Ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate was prepared in Example 11.
    [3899] 1- (2-bromoethoxy) -3-fluorobenzene was prepared according to the method described in Example 15.
    [3900] Example 45
    [3901] 1- [2- (2,3-difluorophenoxy) ethyl] -4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylic acid
    [3902] Ethyl 1- [2- (2,3-difluorophenoxy) ethyl] -4- [3- (3-fluoro-6- in dioxane 3 cm 3 , methanol 3 cm 3 and 5 N sodium hydroxide solution 2.4 cm 3 A mixture of 0.42 g of methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate was stirred at a temperature of 70 ° C. for 17 hours. After cooling to about 20 ° C., the reaction mixture was concentrated to dryness at a temperature of 45 ° C. while slowly decreasing the pressure from 30 kPa to 2.5 kPa. The residue was placed in a 5 cm 3 dichloromethane / methanol / aqueous ammonia mixture (40/5 / 0.5 by volume) and dichloromethane / methanol in a cartridge of silica gel (Bond Elut; particle size 70-200 μ; mass 10 g) under atmospheric pressure. Purification by chromatography, eluting with an aqueous ammonia mixture (90/9 / 0.9 on a volume basis) followed by a chloroform / methanol / aqueous ammonia mixture (77.5 / 19.5 / 3). Fractions containing product were combined, concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. and then dried in a dryer (10 kPa). 0.32 g of 1- [2- (2,3-difluorophenoxy) ethyl] -4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4 -Carboxylic acid was obtained in the form of a white solid.
    [3903] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.34 (broad t, J = 12.5 Hz: 2H); 1.50 to 1.70 (mt: 4H); 1.96 (broad d, J = 12.5 Hz: 2H); 2.09 (broad t, J = 11.5 Hz: 2H); 2.65 (t, J = 6 Hz: 2H); 2.71 (broad d, J = 11.5 Hz: 2H); 3.05 (mt: 2H); 3.97 (s: 3 H); 4.16 (t, J = 6 Hz: 2H); 6.90 to 7.20 (mt: 3H); 7.34 (d, J = 2.5 Hz: 1 H); 7.40 (dd, J = 9 and 2.5 Hz: 1H); 7.97 (d, J = 9 Hz: 1 H); 8.70 (broad s: 1H).
    [3904] Ethyl 1- [2- (2,3-difluorophenoxy) ethyl] -4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxyl Rate
    [3905] 0.4 g of ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate in acetonitrile 15 cm 3 , 1- (2-bromoethoxy)- A mixture of 0.3 g of 2,3-difluorobenzene, 0.181 g of potassium iodide and 0.74 g of potassium carbonate was stirred at a temperature of 70 ° C. for 18 hours. After cooling to about 20 ° C., the reaction mixture was concentrated to dryness at a temperature of 40 ° C. under reduced pressure (5 kPa). The evaporated residue was purified by chromatography, eluting with a mixture of ethyl acetate / 40-60 ° C. petroleum ether (8/2 by volume) in a cartridge of silica gel (Bond Elut; particle size 70-200 μ; mass 12 g) under atmospheric pressure It was. Fractions containing product were combined and concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. 0.43 g of ethyl 1- [2- (2,3-difluorophenoxy) ethyl] -4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine- 4-carboxylate was obtained.
    [3906] ' H NMR Spectrum (500 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 0.99 (mt: 3H); 1.34 (mt: 2 H); 1.40 to 1.60 (mt: 4H); 1.93 (broad d, J = 12.5 Hz: 2H); 1.95 to 2.10 (mt: 2H); 2.45 to 2.70 (mt: 4H); 3.02 (mt: 2H); 3.93 (s: 3 H); 3.95 (mt: 2 H); 4.12 (mt: 2 H); 6.85 to 7.05 (mt: 2H); 7.09 (mt: 1 H); 7.31 (broad s: 1H); 7.37 (broad d, J = 9 Hz: 1H); 7.94 (d, J = 9 Hz: 1H); 8.66 (broad s: 1H).
    [3907] Ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate was prepared in Example 11.
    [3908] 1- (2-bromoethoxy) -2,3-difluorobenzene was prepared according to the method described in Example 17.
    [3909] Example 46
    [3910] 4- [3- (3-fluoroquinolin-4-yl) propyl] -1- [2- (thien-2-yl) -thioethyl] piperidine-4-carboxylic acid
    [3911] Ethyl 4- [3- (3-fluoro-quinolin-4-yl) propyl] -1- [2- (thien-2-yl) thio in dioxane 65 cm 3 , methanol 65 cm 3 and 5 N aqueous sodium hydroxide solution 8 cm 3 A mixture of 1.29 g of ethyl] piperidine-4-carboxylate was stirred at a temperature of 70 ° C. for 20 hours. To the reaction mixture was added 8 cm 3 of 5N aqueous sodium hydroxide solution, which was further stirred at a temperature of 70 ° C. for 6 hours. After cooling to about 20 ° C, the reaction was concentrated to dryness under reduced pressure (2 kPa) at a temperature of 50 ° C. The residue was purified by chromatography, eluting with a chloroform / methanol / aqueous ammonia mixture (12/3 / 0.5 by volume) under a column of silica gel (particle size 20-45 μ; diameter 6 cm; height 30 cm) under atmospheric pressure. -cm 3 was collected. Fractions 8 to 24 were combined and concentrated to dryness at a temperature of 40 ° C. under reduced pressure (2 kPa). The white solid was placed in 60 cm 3 of diisopropyl ether and stirred at a temperature of 20 ° C. for 18 hours. The suspension was filtered, washed three times with 15 cm 3 of diisopropyl ether, followed by rotary filtration and drying under reduced pressure (10 kPa) at about 50 ° C. Melting 0.8 g of 4- [3- (3-fluoroquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] piperidine-4-carboxylic acid at 180 ° C Obtained in the form of a white solid.
    [3912] ' H NMR Spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.27 (mt: 2H); 1.56 (mt: 4H); 1.85 to 2.05 (mt: 4H); 2.44 (broad t, J = 7Hz: 2H); 2.57 (mt: 2 H); 2.90 (broad t, J = 7Hz: 2H); 3.06 (unisolated peak: 2H); 7.04 (dd, J = 5.5 and 3.5 Hz: 1H); 7.17 (dd, J = 3.5 and 1.5 Hz: 1H); 7.60 (dd, J = 5.5 and 1.5 Hz: 1H); 7.71 (broad t, J = 7.5 Hz: 1H); 7.77 (broad t, J = 7.5 Hz: 1H); 8.08 (broad d, J = 7.5 Hz: 1H); 8.15 (broad d, J = 7.5 Hz: 1H); 8.89 (d, J = 1.5 Hz: 1 H).
    [3913] Ethyl 4- [3- (3-fluoroquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] piperidine-4-carboxylate
    [3914] 1.8 g of ethyl 1- (2-chloroethyl) -4- [3- (3-chloroquinolin-4-yl) propyl] piperidine-4-carboxylate monohydrochloride in 200 cm 3 anhydrous acetonitrile A mixture of fen-2-thiol 0.48 cm 3 , potassium carbonate 2.8 g and potassium iodide 0.75 g was stirred under an inert atmosphere at a temperature of 70 ° C. After cooling to 20 ° C., the suspension was filtered, washed three times with 30 cm 3 of acetonitrile and the filtrate was concentrated to dryness under reduced pressure (2 kPa) at a temperature of 50 ° C. The evaporated residue was purified by chromatography eluting with ethyl acetate on a column of silica gel (particle size 20-45 μ; diameter 6 cm; height 30 cm) under atmospheric pressure to collect 50-cm 3 fractions. Fractions 25 to 52 were combined and then concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. 1.3 g of ethyl 4- [3- (3-fluoroquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] piperidine-4-carboxylate is viscous orange Obtained in the form of an oil.
    [3915] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 0.99 (t, J = 7 Hz: 3H); 1.34 (very broad t, J = 13 Hz: 2H); 1.56 (mt: 4H); 1.85 to 2.00 (mt: 4H); 2.45 (broad t, J = 7Hz: 2H); 2.59 (broad d, J = 11.5 Hz: 2H); 2.90 (broad t, J = 7Hz: 2H); 3.07 (broad t, J = 6.5 Hz: 2H); 3.95 (q, J = 7 Hz: 2H); 7.04 (dd, J = 5.5 and 3.5 Hz: 1H); 7.17 (dd, J = 3.5 and 1.5 Hz: 1H); 7.60 (dd, J = 5.5 and 1.5 Hz: 1H); 7.70 (broad t, J = 7.5 Hz: 1H); 7.77 (heterogeneous triplet, J = 7.5 and 1.5 Hz: 1H); 8.08 (broad d, J = 7.5 Hz: 1H); 8.13 (broad d, J = 7.5 Hz: 1H); 8.89 (d, J = 1 Hz: 1H).
    [3916] Ethyl 1- (2-chloroethyl) -4- [3- (3-fluoroquinolin-4-yl) -propyl] piperidine-4-carboxylate hydrochloride
    [3917] Thionyl chloride 1.2 cm 3 in dichloromethane 5 cm 3 to ethyl 4- [3- (3-fluoroquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thio in dichloromethane 35 cm 3 To a solution of 1.55 g of ethyl] piperidine-4-carboxylate was added while stirring at a temperature of 20 ° C. After stirring for 42 hours at a temperature of 20 ° C., the reaction mixture was concentrated to dryness under about 50 ° C. under reduced pressure (1.2 kPa). The obtained foam was put three times in 100 cm 3 of cyclohexane, concentrated to dryness at a temperature of 40 ° C. under reduced pressure (2 kPa), and then oven-dried under reduced pressure (10 kPa) at a temperature of 40 ° C. 1.8 g of ethyl 1- (2-chloroethyl) -4- [3- (3-fluoroquinolin-4-yl) -propyl] piperidine-4-carboxylate monohydrochloride are obtained in the form of a cream solid. It was.
    [3918] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.03 (t, J = 7 Hz: 3H); 1.45 to 2.10 (mt: 6H); 2.16 (broad d, J = 14 Hz: 2H); 2.70 to 3.00 (mt: 2H); 3.12 (mt: 2 H); 3.40 to 3.55 (mt: 4H); 3.95 to 4.10 (mt: 4H); 7.72 (broad t, J = 7.5 Hz: 1H); 7.79 (broad t, J = 7.5 Hz: 1H); 8.09 (broad d, J = 7.5 Hz: 1H); 8.18 (broad d, J = 7.5 Hz: 1H); 8.92 (broad s: 1H); 10.10 to 10.35 (unseparated peak: 1H).
    [3919] Ethyl 4- [3- (3-fluoroquinolin-4-yl) propyl] -1- (2-hydroxy-ethyl) piperidine-4-carboxylate
    [3920] To Figure 2-iodo ethanol 1.14cm 3, and 1.9g of potassium carbonate in anhydrous acetonitrile, ethyl 4 of 100cm 3 [3- (3-Fluoro-4-yl) propyl] piperidine-4-carboxylate 4.4g of The solution was added with vigorous stirring under inert atmosphere. The reaction mixture was stirred at a temperature of 20 ° C. for 18 hours, filtered and washed three times with 30 cm 3 of acetonitrile. The filtrate was concentrated to dryness under reduced pressure (2 kPa) at a temperature of 50 ° C. The evaporated residue was purified by chromatography, eluting with dichloromethane / methanol / aqueous ammonia (40/5 / 0.5 by volume) in a column of silica gel (particle size 20-45 μ; diameter 5 cm; height 32 cm) under atmospheric pressure to 100 -cm 3 fractions were collected. Fractions 8-12 were combined and then concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. 3.5 g of ethyl 4- [3- (3-fluoroquinolin-4-yl) propyl] -1- (2-hydroxyethyl) piperidine-4-carboxylate were obtained in the form of a viscous orange oil. .
    [3921] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 0.99 (t, J = 7 Hz: 3H); 1.36 (mt: 2 H); 1.57 (mt: 4H); 1.85 to 2.05 (mt: 4H); 2.29 (t, J = 6.5 Hz: 2H); 2.61 (d mt, J = 12 Hz: 2H); 3.08 (broad t, J = 6Hz: 2H); 3.45 (mt: 2 H); 3.96 (q, J = 7 Hz: 2H); 4.31 (t, J = 5.5 Hz: 1H); 7.70 (broad t, J = 7.5 Hz: 1H); 7.77 (heterogeneous triplet, J = 7.5 and 1.5 Hz: 1H); 8.08 (dd, J = 7.5 and 1.5 Hz: 1H); 8.14 (dd, J = 7.5 and 1.5 Hz: 1H); 8.89 (d, J = 1 Hz: 1H).
    [3922] Ethyl 4- [3- (3-fluoroquinolin-4-yl) propyl] piperidine-4-carboxylate
    [3923] D. A solution of 4M hydrogen chloride in dioxane 50cm 3 150cm 3 of anhydrous dioxane, ethyl 4 of [3- (3-Fluoro-4-yl) propyl] -1- (tert-butyloxycarbonyl) piperidine Carefully added to a solution of 8.7 g of -4-carboxylate and kept below 30 ° C. during the addition of temperature. After stirring for 18 h at a temperature of 20 ° C., the suspension is diluted with 250 cm 3 of diethyl ether, filtered and washed five times with 50 cm 3 of diethyl ether, and the solid is washed under 20 ° C. under reduced pressure (2 kPa). It was dried in a dryer at the temperature. The solid was placed in 50 cm 3 of water and the pH was adjusted to about 10 by addition of 5N saturated sodium hydroxide solution. The mixture was then extracted five times with 100 cm 3 of diethyl ether. The organic phases were combined, dried over magnesium sulfate, placed in plant charcoal (3S), filtered and concentrated to dryness under reduced pressure (2 kPa) at a temperature of 50 ° C. 4.7 g of ethyl 4- [3- (3-fluoroquinolin-4-yl) propyl] piperidine-4-carboxylate were obtained in the form of a viscous orange oil.
    [3924] Mass spectrum: EI m / z = 344 M + m / z = 288 C 17 H 19 FNO 2 +.
    [3925] m / z = 184 C 10 H 18 NO 2 +.
    [3926] Reference peak m / z = 161 C 10 H 8 FN +
    [3927] Ethyl 4- [3- (3-fluoroquinolin-4-yl) propyl] -1- (tert-butyloxycarbonyl) piperidine-4-carboxylate
    [3928] 17.7 g of ethyl 4-allyl-1- (tert-butylhydroxycarbonyl) piperidine-4-carboxylate in tetrahydrofuran 200cm 3 was cooled to a temperature of -30 ° C and 9-bora in tetrahydrofuran Bicyclo [3.3.1] nonane 0.5 M solution 135 cm 3 was added under stirring under inert atmosphere. After addition, the temperature of the mixture was reduced to a temperature of about 20 ° C. and the mixture was stirred for 2 hours. 14.8 g of 3-fluoro-4-iodoquinoline in tetrahydrofuran 430 cm 3 , 1.3 g of palladium diphenylphosphinoferrocene chloride and 29.8 g of trivalent potassium phosphate were added. The reaction mixture was heated to a temperature of 70 ° C. for 20 hours. After cooling to 20 ° C., the reaction was filtered and washed three times with 100 cm 3 of tetrahydrofuran. The filtrate was concentrated to dryness at a temperature of 40 ° C. under reduced pressure (2 kPa). After evaporation the residue was placed in a 500cm 3 of diethyl ether, washed three times with diethyl ether and the insoluble material 100cm 3, The filtrate was concentrated to dryness under reduced pressure (2kPa) at a temperature of 40 ℃. The oil obtained was purified by chromatography, eluting with a dichloromethane / ethyl acetate mixture (90/10 by volume) in a column of silica gel (particle size 20-45 μ; diameter 6 cm; height 45 cm) under atmospheric pressure. 3 fractions were collected. Fractions 30 to 76 were combined and then concentrated to dryness under the same conditions as above. 13.7 g of ethyl 4- [3- (3-fluoroquinolin-4-yl) propyl] -1- (tert-butyloxycarbonyl) piperidine-4-carboxylate in the form of a viscous orange oil Obtained.
    [3929] Mass spectrum: EI m / z = 444 M +. m / z = 388 [M−tBu] +.
    [3930] m / z = 343 [M-BOC] +
    [3931] m / z = 288 C 17 H 19 FNO 2 +. m / z = 184
    [3932] C 10 H 18 NO 2 +.
    [3933] m / z = 161 C 10 H 8 FN + m / z = 57 C 4 H 9 +
    [3934] 3-fluoro-4-iodoquinoline
    [3935] 650cm 3 of tetrahydrofuran cooled to di-isopropyl amine 17.3cm 3 to a temperature of -75 ℃ of butyllithium 1.6M solution and 76cm 3 of hexane maintaining a temperature of about -70 ℃, and while stirring under an inert atmosphere was added . After 20 minutes of stirring at a temperature of -75 ° C, a solution of 11.9 g of 3-fluoroquinoline in 200 cm 3 of tetrahydrofuran was added. The obtained solution was stirred at -75 ° C for an additional 4 hours and then tetrahydro A solution of 32.2 g of double-sublimated iodine in furan 150 cm 3 was added. After stirring for 2 hours at a temperature of -40 ℃, the reaction mixture was 90/10 (volume basis) in tetrahydrofuran / water mixture of 200cm 3 was then hydrolyzed with a saturated sodium chloride solution of 200cm 3. At a temperature of 20 ° C., the mixture was diluted with 300 cm 3 of ethyl acetate and washed twice with 250 cm 3 of saturated sodium chloride solution. The organic phase was dried over magnesium sulfate, then filtered and concentrated to dryness under reduced pressure (2 kPa) at a temperature of 50 ° C. The obtained residue was purified by chromatography eluting with dichloromethane on a column of silica gel (particle size 20-45 μ; diameter 10 cm; height 30 cm) under atmospheric pressure to collect 100-cm 3 fractions. Fractions 45 to 80 were combined and concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. 15.1 g of 3-fluoro-4-iodoquinoline were obtained in the form of a cream solid which melts at 110 ° C.
    [3936] Mass spectrum: EI m / z = 273 M +. Reference peak m / z = 146
    [3937] [M-I] +
    [3938] 3-fluoroquinoline
    [3939] 23.5 g of 3-aminoquinoline and 12.1 g of sodium nitrite in 20 cm 3 of distilled water were carefully added to 100 cm 3 of tetrafluoroboric acid cooled to 0 ° C. with vigorous stirring, and the reaction mixture was stirred for 30 minutes. The suspension was filtered, rotary-filtered and washed three times with 30 cm 3 of ice cold tetrafluoroboric acid, four times with 50 cm 3 of ice cold ethanol and 30 cm 3 of diethyl ether. The solid was dried in a 20 ° C. dryer (2 kPa) and then placed in 200 cm 3 of toluene and heated for 1 hour while stirring to a temperature of 90 ° C. After cooling to about 20 ° C., the phases of the reactants were separated by sedimentation, the insoluble oil was washed three times with 100 cm 3 of toluene and poured into 110 cm 3 of water, and then slowly added sodium bicarbonate to give a pH of about 8 basic. Make it. The aqueous phase is extracted five times with 100 cm 3 of diethyl ether, the organic phases are combined, washed twice with 50 cm 3 of water, dried over magnesium sulfate, put into plant charcoal (3S), filtered and then at a temperature of 45 ° C. It was concentrated to dryness under reduced pressure (2 kPa). The oil was placed in 50 cm 3 of 40-60 ° C. petroleum ether / ethyl acetate mixture (90/10 by volume), and the insoluble material was filtered off, then 40 cm of 60-60 ° C. petroleum ether / ethyl acetate mixture (90/10 by volume) Washed twice with 3 and then dried in a drier under reduced pressure (2 kPa) at a temperature of 20 ° C. The filtrate was concentrated to dryness at a temperature of 40 ° C. under reduced pressure (2 kPa). The residue obtained was purified by chromatography, eluting with a petroleum ether / ethyl acetate mixture (90/10 by volume) in a column of silica gel (particle size 20-45 μ; diameter 5 cm; height 45 cm) under atmospheric pressure. 3 fractions were collected. Fractions 20 to 31 were combined and concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. 13 g of 3-fluoroquinoline were obtained in colorless liquid form.
    [3940] Mass spectrum: EI m / z = 147 M +. Reference peak m / z = 127
    [3941] [M-HF] +.
    [3942] m / z = 120 [M-HCN] +
    [3943] Ethyl 4-allyl-1- (tert-butylhydroxycarbonyl) piperidine-4-carboxylate was prepared in Example 1.
    [3944] Example 47
    [3945] Viscosity ethyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (pyridin-2-yloxy) ethyl] piperidine-4-carboxylate Prepared in the form of a colorless oil.
    [3946] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.04 (t, J = 7 Hz: 3H); 1.39 (very broad t, J = 12 Hz: 2H); 1.51 (mt: 2 H); 1.68 (mt: 2 H); 1.90 to 2.15 (mt: 4H); 2.60 (t, J = 6 Hz: 2H); 2.70 (broad d, J = 12 Hz: 2H); 3.16 (broad t, J = 7.5 Hz: 2H); 3.95 (s: 3 H); 3.99 (q, J = 7 Hz: 2H); 4.31 (t, J = 6 Hz: 2H); 6.78 (d, J = 8 Hz: 1H); 6.96 (broad dd, J = 7.5 and 5 Hz: 1H); 7.37 (d, J = 2.5 Hz: 1 H); 7.45 (dd, J = 9 and 2.5 Hz: 1H); 7.69 (ddd, J = 8-7.5 and 2 Hz: 1H); 7.96 (d, J = 9 Hz: 1H); 8.14 (broad dd, J = 5 and 2 Hz: 1H); 8.67 (s: 1 H).
    [3947] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridin-2-yloxy) ethyl] piperidine-4-carboxylic acid
    [3948] Ethyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (pyridine-2-) in dioxane 3 cm 3 , methanol 5 cm 3 and 5 N aqueous sodium hydroxide solution 1 cm 3 A mixture of 0.12 g of yloxy) -ethyl] piperidine-4-carboxylate was stirred at a temperature of 70 ° C. for 21 hours. After cooling to about 20 ° C., the reaction mixture was concentrated to dryness at a temperature of 60 ° C. under reduced pressure (5 kPa). The residue was taken up in a 5 cm 3 dichloromethane / methanol / aqueous ammonia mixture (40/5 / 0.5 by volume), then dichloromethane in a column of silica gel (particle size 70-200 μ; diameter 1.5 cm; mass 20 g) under atmospheric pressure Purification by chromatography eluting with a methane / methanol / aqueous ammonia mixture (40/5 / 0.5 by volume). Fractions containing product were combined and concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. The foam was placed in 2 cm 3 of methanol, filtered and washed with 1 cm 3 of methanol and 2 cm 3 of diethyl ether, followed by oven-drying under reduced pressure (10 kPa) at about 50 ° C. 0.115 g of 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2-pyridin-2-yloxy) ethyl] piperidine-4-carboxylic acid Melt at &lt; RTI ID = 0.0 &gt;
    [3949] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.20 to 1.80 (mt: 6H); 1.98 (very broad d, J = 13.5 Hz: 2H); 2.09 (very broad t, J = 11 Hz: 2H); 2.60 (t, J = 6 Hz: 2H); 2.67 (mt: 2 H); 3.16 (mt: 2 H); 3.98 (s: 3 H); 4.32 (t, J = 6 Hz: 2H); 6.80 (d, J = 8 Hz: 1H); 6.96 (ddd, J = 7.5-5 and 1 Hz: 1H); 7.39 (broad s: 1H); 7.45 (dd, J = 9 and 2.5 Hz: 1H); 7.70 (ddd, J = 8-7.5 and 2 Hz: 1H); 7.97 (d, J = 9 Hz: 1 H); 8.16 (broad dd, J = 5 and 2 Hz: 1H); 8.67 (s: 1 H).
    [3950] Example 48
    [3951] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -3- (R, S) -fluoropropyl] -1- [2- (2,5-difluorophenylthio) Ethyl] -piperidine-4-carboxylic acid
    [3952] Dioxane 3cm 3, 3cm 3 of methanol and 5N sodium hydroxide aqueous solution of methyl 0.9cm 3 4- [3- (3- chloro-6-methoxy-quinolin-4-yl) -3- (R, S) - fluoro-propyl A mixture of 0.07 g of] -1- [2- (2,5-difluorophenylthio) ethyl] piperidine-4-carboxylate was maintained at a temperature of 70 ° C. for 4 hours. After cooling to about 20 ° C., the reaction mixture was concentrated to dryness at a temperature of 40 ° C. under reduced pressure (2 kPa). The residue was purified by chromatography eluting with a dichloromethane / methanol / aqueous ammonia mixture (40/5 / 0.5 by volume) on a column of silica gel (particle size 70-200 μ; mass 10 g) under atmospheric pressure. Fractions 10 to 15 were combined and concentrated to dryness under the same conditions as above. 0.04 g of 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -3- (R, S) -fluoropropyl] -1- [2- (2,5-difluoro Phenylthio) ethyl] piperidine-4-carboxylic acid was obtained in the form of a white solid.
    [3953] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.20 to 2.60 (mt: 12H); 2.66 (mt: 2 H); 3.03 (t, J = 7 Hz: 2H); 3.93 (s: 3 H); 6.38 (mt, J HF = 48 Hz: 1H); 7.05 (mt: 1 H); 7.20 to 7.40 (mt: 2H); 7.52 (dd, J = 9 and 2.5 Hz: 1H); 7.56 (d, J = 2.5 Hz: 1 H); 8.04 (d, J = 9 Hz: 1H); 8.75 (broad s: 1H); 12.30 to 12.70 (broad unseparated peak: 1H).
    [3954] Methyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -3- (R, S) -fluoropropyl] -1- [2- (2,5-difluorophenylthio Ethyl] -piperidine-4-carboxylate
    [3955] Diethylamino-sulfur trimethyl dichloromethane 10cm 3 fluoride 0.1cm 3 4- [3- (3- chloro-6-methoxy-quinolin-4-yl) -3- (R, S) - hydroxypropyl] To a solution of 0.25 g of -1- [2- (2,5-difluorophenylthio) ethyl] piperidine-4-carboxylate, it was added with stirring under an inert atmosphere at a temperature of 5 ° C. After stirring for 7 hours at a temperature of 20 ℃, saturated sodium hydrogen carbonate solution was added to the reaction mixture. The aqueous phase was extracted with dichloromethane. The organic phase was dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. The residue obtained was subjected to dichloromethane 60 cm 3 , ethyl acetate / dichloromethane mixture (1/9 by volume) 45 cm 3 , ethyl acetate / dichloromethane mixture in a column of silica gel (at particle size 70-200 μ; mass 15 g) under atmospheric pressure. (volume basis to 2/8) 30cm 3, and it was purified by ethyl acetate / dichloromethane mixture and chromatography (3/7 by volume basis), eluting successively with our 210cm 3. Fractions 24 to 26 were combined and concentrated to dryness under the same conditions as above. 0.08 g of methyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -3- (R, S) -fluoropropyl] -1- [2- (2,5-difluoro Rophenylthio) ethyl] piperidine-4-carboxylate was obtained in the form of a dark yellow oil.
    [3956] 1 H NMR spectrum (400 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.20 to 2.60 (mt: 12H); 2.55 to 2.75 (mt: 2H); 3.11 (t, J = 7 Hz: 2H); 3.54 (s: 3 H); 3.93 (s: 3 H); 6.36 (mt, J HF = 48 Hz: 1H); 7.05 (mt: 1 H); 7.15 to 7.35 (mt: 2H); 7.45 to 7.55 (mt: 2H); 8.03 (d, J = 9 Hz: 1H); 8.75 (s: 1 H).
    [3957] Methyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -3- (R, S) -hydroxypropyl] -1- [2- (2,5-difluorophenylthio Ethyl] -piperidine-4-carboxylate
    [3958] 1.75 g of ethyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate in acetonitrile 30 cm 3 and dimethylformamide 20 cm 3 A mixture of 0.95 g bromoethylthio) -1,4-difluorobenzene, 0.622 g potassium iodide and 30 m 3 of potassium carbonate was heated to a temperature of 85 ° C. for 18 hours with stirring. After cooling to about 20 ° C, the reaction mixture was filtered through celite and the filtrate was concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. The obtained residue is taken up in diethyl ether and water. The organic phase was dried over magnesium sulfate, then filtered and concentrated to dryness under the above conditions. The residue obtained was purified by chromatography, eluting with a dichloromethane / methanol mixture (97.5 / 2.5 on a volume basis) in a column of silica gel (particle size 70-200 μ; diameter 4 cm) under atmospheric pressure. Fractions containing product were combined and concentrated to dryness under the above conditions. 0.6 g of methyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -3- (R, S) -hydroxypropyl] -1- [2- (2,5-difluoro Rophenylthio) ethyl] piperidine-4-carboxylate was obtained.
    [3959] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.20 to 2.15 (mt: 10H); 2.45 to 2.55 (mt: 2H); 2.64 (mt: 2 H); 3.12 (t, J = 7 Hz: 2H); 3.47 (s: 3 H); 3.87 (s: 3 H); 5.41 (mt: 1 H); 6.10 (unisolated peak: 1H); 7.04 (mt: 1 H); 7.15 to 7.35 (mt: 2H); 7.45 (dd, J = 9 and 2.5 Hz: 1H); 7.97 (d, J = 9 Hz: 1 H); 8.13 (very broad d, J = 2.5 Hz: 1H); 8.66 (s: 1 H).
    [3960] 2- (2-bromoethylthio) -1,4-difluorobenzene can be obtained by applying the method described in Example 14.
    [3961] Methyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -3- (R, S) -hydroxypropyl] piperidine-4-carboxylate was prepared in Example 49.
    [3962] Example 49
    [3963] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -3- (R, S) -fluoropropyl] -1- [2- (2,5-difluorophenoxy) Ethyl] piperidine-4-carboxylic acid
    [3964] Ethyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -3- (R, S) -fluoropropyl] in dioxane 3 cm 3 , methanol 3 cm 3 and 5 N aqueous sodium hydroxide solution 1 cm 3 A mixture of 0.15 g of -1- [2- (2,5-difluorophenoxy) ethyl] piperidine-4-carboxylate was maintained at a temperature of 70 ° C. for 4 hours. After cooling to about 20 ° C., the reaction mixture was concentrated to dryness at a temperature of 40 ° C. under reduced pressure (2 kPa). The residue was subjected to dichloromethane / methanol / aqueous ammonia mixture (40/5 / 0.5 by volume) and dichloromethane / methanol / aqueous in Bond Elut (particle size 70-200 μ; mass 25 g) of silica gel 60 cm 3 under atmospheric pressure of 60 kPa. Chromatography eluting with an ammonia mixture (40/5/2 by volume) in turn. Fractions containing the expected product were combined and concentrated to dryness under the same conditions as above. 0.04 g of 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -3- (R, S) -fluoropropyl] -1- [2- (2,5-difluoro Phenoxy) ethyl] piperidine-4-carboxylic acid was obtained in the form of a white solid.
    [3965] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.20 to 2.40 (mt: 10H); 2.65 (t, J = 6 Hz: 2H); 2.72 (mt: 2 H); 3.93 (s: 3 H); 4.03 (t, J = 6 Hz: 2H); 6.37 (mt, J HF = 48 Hz: 1H); 6.75 (mt: 1 H); 7.14 (mt: 1 H); 7.25 (mt: 1 H); 7.52 (dd, J = 9 and 2.5 Hz: 1H); 7.56 (d, J = 2.5 Hz: 1 H); 8.03 (d, J = 9 Hz: 1 H); 8.75 (d, J = 1 Hz: 1H).
    [3966] Methyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -3- (R, S) -fluoropropyl] -1- [2- (2,5-difluorophenoxy Ethyl] piperidine-4-carboxylate
    [3967] Diethylamino-sulfur trifluoride in a 0.2cm 3-methyl dichloromethane 20cm 3 4- [3- (3- chloro-6-methoxy-quinolin-4-yl) -3- (R, S) - hydroxypropyl] To a solution of 0.5 g of -1- [2- (2,5-difluorophenoxy) ethyl] piperidine-4-carboxylate was added while stirring under an inert atmosphere at a temperature of 3 ° C. After stirring for 7 hours at a temperature of 20 ℃, saturated sodium hydrogen carbonate solution was added to the reaction mixture. The aqueous phase was extracted with dichloromethane. The organic phase was dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. The obtained residue was chromatographed under atmospheric pressure with a column of silica gel (particle size 70-200 μ; diameter 1.5 cm; mass 15 g) with an ethyl acetate / petroleum ether (40-60 ° C.) (8/2 by volume) mixture. It was purified by chromatography. Fractions 9-11 were combined and concentrated to dryness under the same conditions as above. 0.21 g of methyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -3- (R, S) -fluoropropyl] -1- [2- (2,5-difluoro Rophenoxy) ethyl] piperidine-4-carboxylate was obtained in the form of a dark yellow oil.
    [3968] Mass spectrum: DCI m / z = 551 MH +
    [3969] The presence of impurities m '= 532.
    [3970] Methyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -3- (R, S) -hydroxypropyl] -1- [2- (2,5-difluorophenoxy Ethyl] -piperidine-4-carboxylate
    [3971] 1.55 g of methyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -3-hydroxypropyl] piperidine-4-carboxylate in acetonitrile 30 cm 3 and dimethylformamide 20 cm 3 , A mixture of 1.03 g of 1- (2-bromoethoxy) -2,5-difluorobenzene, 0.65 g of potassium iodide and 2.7 g of potassium carbonate was heated to a temperature of 85 ° C. for 17 hours with stirring. After cooling to 20 ° C., the reaction mixture was filtered through celite and the filtrate was concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. Evaporate the residue into dichloromethane and water. The organic phase was dried over magnesium sulfate, then filtered and concentrated to dryness under the above conditions. The residue was purified by chromatography eluting with a dichloromethane / methanol mixture (97/3 by volume) on a column of silica gel (particle size 70-200 μ; diameter 4 cm) under atmospheric pressure. Fractions containing product were combined and concentrated to dryness at a temperature of 40 ° C., under reduced pressure (2 kPa) and under the same conditions as above. 0.5 g of methyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -3- (R, S) -hydroxypropyl] -1- [2- (2,5-difluoro Rophenoxy) ethyl] piperidine-4-carboxylate was obtained.
    [3972] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.20 to 2.20 (mt: 10H); 2.60 to 2.80 (mt: 2H); 2.64 (t, J = 6 Hz: 2H); 3.48 (s: 3 H); 3.88 (s: 3 H); 4.12 (t, J = 6 Hz: 2H); 5.40 (mt: 1 H); 6.10 (broad s: 1H); 6.74 (mt: 1 H); 7.13 (mt: 1 H); 7.24 (mt: 1 H); 7.44 (dd, J = 9 and 2.5 Hz: 1H); 7.96 (d, J = 9 Hz: 1H); 8.14 (d, J = 2.5 Hz: 1H); 8.66 (s: 1 H).
    [3973] Methyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -3- (R, S) -hydroxypropyl] piperidine-4-carboxylate
    [3974] Methyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -3- (R, S) -hydroxypropyl]-(tert-butyloxycarbonyl) piperi in methanol 100 cm 3 A mixture of 2.95 g of dean-carboxylate and 2.3 cm 3 of sulfuric acid is heated at 80 ° C. for 1 hour 30 minutes. After cooling, the reaction mixture was concentrated to dryness at a temperature of 40 ° C. under reduced pressure (2 kPa). The residue was taken up in 10 cm 3 of water, and the pH was made basic with a saturated sodium bicarbonate solution followed by a saturated sodium carbonate solution, and then concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. The obtained residue was purified by chromatography, eluting with a chloroform / methanol / aqueous ammonia mixture (12/3 / 0.5 on a volume basis) in a column of silica gel (particle size 20-45 μ; diameter 2 cm; volume 80 cm 3 ) under atmospheric pressure. It was. Fractions 8-20 were combined and concentrated to dryness under the same conditions as above. 1.37 g of methyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -3- (R, S) -hydroxypropyl] piperidine-4-carboxylate in the form of a cream colored foam Obtained.
    [3975] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.10 to 1.45 (mt: 3H); 1.55 to 1.75 (mt: 1 H); 1.80 to 2.05 (mt: 4H); 2.40 (mt: 2 H); 2.72 (mt: 2 H); 3.50 (s: 3 H); 3.90 (s: 3 H); 5.42 (broad t, J = 6.5 Hz: 1H); 6.09 (mt: 1 H); 7.45 (dd, J = 9 and 3 Hz: 1H); 7.97 (d, J = 9 Hz: 1 H); 8.15 (d, J = 3 Hz: 1H); 8.67 (s: 1 H).
    [3976] Methyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -3- (R, S) -hydroxypropyl]-(tert-butyloxycarbonyl) piperidine carboxylate
    [3977] Ethyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -propyl]-(tert-butyloxycarbonyl) piperidine in dimethyl sulfoxide 400cm 3 and tert-butanol 120cm 3 A solution of 5 g of -4-carboxylate was stirred under oxygen-saturated atmosphere at a temperature of 20 ° C. After 5 minutes, a solution of 2.8 g of potassium tert-butoxide in 30 cm 3 of tert-butanol was added to the reaction mixture. After oxygen was charged for 2 hours, 300 cm 3 of ice cold water and 3.5 cm 3 of acetic acid were carefully added. The aqueous phase was extracted twice with 200 cm 3 of dichloromethane. The organic phases were combined and washed four times with 1 dm 3 of water. The organic phase was concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. The residue was taken up in 200 cm 3 of diethyl ether, filtered off, washed with 20 cm 3 of diethyl ether, and dried in a drier under reduced pressure (0.1 kPa) at a temperature of 40 ° C. 3 g of methyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -3- (R, S) -hydroxypropyl]-(tert-butyloxycarbonyl) piperidine carboxyl The rate was obtained in the form of a white solid that melts at 222 ° C.
    [3978] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.10 to 1.50 (mt: 3H); 1.39 (s: 9 H); 1.70 (mt: 1 H); 1.80 to 2.10 (mt: 4H); 2.81 (mt: 2 H); 3.69 (mt: 2 H); 3.89 (s: 3 H); 5.41 (dd, J = 9 and 5 Hz: 1H); 5.80 to 6.30 (broad unseparated peak: 1H); 7.44 (dd, J = 9 and 3 Hz: 1H); 7.95 (d, J = 9 Hz: 1H); 8.16 (d, J = 3 Hz: 1H); 8.65 (s: 1 H); 12.00 to 12.90 (broad unseparated peak: 1H).
    [3979] 1- (2-bromoethoxy) -2,5-difluorobenzene was prepared in Example 16.
    [3980] Ethyl 4- [3- (3-chloro-6-methoxyquinolinyl) -propyl] -1- (tert-butoxycarbonyl) piperidine-4-carboxylate was prepared in Example 5.
    [3981] Example 50
    [3982] Ethyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) -propyl] -1- [2- (thiazol-2-yloxy) ethyl] piperidine-4-carboxylate Prepared.
    [3983] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.05 (t, J = 7 Hz: 3H); 1.40 (very broad t, J = 12 Hz: 2H); 1.53 (mt: 2 H); 1.69 (mt: 2 H); 1.90 to 2.15 (mt: 4H); 2.64 (t, J = 5.5 Hz: 2H); 2.70 (broad d, J = 11.5 Hz: 2H); 3.16 (broad t, J = 7.5 Hz: 2H); 3.96 (s: 3 H); 4.01 (q, J = 7 Hz: 2H); 4.42 (t, J = 5.5 Hz: 2H); 7.04 (d, J = 3.5 Hz: 1H); 7.17 (d, J = 3.5 Hz: 1 H); 7.37 (d, J = 2.5 Hz: 1H); 7.46 (dd, J = 9 and 2.5 Hz: 1H); 7.97 (d, J = 9 Hz: 1 H); 8.67 (s: 1 H).
    [3984] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (thiazol-2-yloxy) ethyl] piperidine-4-carboxylic acid
    [3985] Ethyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (thiazole-2 in dioxane 7 cm 3 , methanol 9 cm 3 and 5 N aqueous sodium hydroxide solution 2 cm 3 A mixture of 0.68 g of -yloxy) -ethyl] piperidine-4-carboxylate was maintained at a temperature of 60 ° C. for 20 hours. After cooling to about 20 ° C., the reaction was concentrated to dryness at a temperature of 40 ° C. under reduced pressure (2 kPa). The obtained residue was chromatographed, eluting with a dichloromethane / methanol mixture (70/30 by volume) in a column of silica gel (particle size 20-45 μ; diameter 2.2 cm; mass 20 g) under a pressure of 50 kPa argon. Fractions containing the expected product were combined and concentrated to dryness under the above conditions. The obtained residue was taken in ethyl acetate 5cm 3 , stirred at room temperature for 1 hour, then filtered, washed three times with 3cm 3 of ethyl acetate, and washed three times with 3cm 3 of pentane. 0.27 g of 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2-thiazol-2-yloxy) ethyl] piperidine-4-carboxylic acid 188 Obtained in the form of a white solid which melts at &lt; RTI ID = 0.0 &gt;
    [3986] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.39 (broad t, J = 12 Hz: 2H); 1.50 to 1.65 (mt: 2H); 1.71 (mt: 2 H); 1.98 (broad d, J = 12 Hz: 2H); 2.12 (unseparated peak: 2H); 2.60 to 2.85 (mt: 4H); 3.17 (broad t, J = 7.5 Hz: 2H); 3.96 (s: 3 H); 4.45 (very broad t, J = 5.5 Hz: 2H); 7.05 (d, J = 3.5 Hz: 1H); 7.18 (d, J = 3.5 Hz: 1 H); 7.37 (d, J = 2.5 Hz: 1 H); 7.46 (dd, J = 9 and 2.5 Hz: 1H); 7.97 (d, J = 9 Hz: 1 H); 8.68 (s: 1 H); 11.80 to 12.70 (broad unseparated peak: 1H).
    [3987] Example 51
    [3988] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4,5-dihydrothiazol-2-ylthio) ethyl] piperidine- 4-carboxylic acid
    [3989] Ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4,5 in dioxane 5 cm 3 , methanol 5 cm 3 and 5 N aqueous sodium hydroxide solution 1 cm 3 A mixture of 0.15 g of dihydrothiazol-2-ylthio) ethyl] piperidine-4-carboxylate was maintained at a temperature of 75 ° C. for 20 hours. After cooling to about 20 ° C., the reaction mixture was concentrated to dryness at a temperature of 40 ° C. under reduced pressure (2 kPa). The obtained residue was purified by chromatography, eluting with a dichloromethane / methanol / aqueous ammonia mixture (40/5 / 0.5 by volume) in a column of silica gel (Bond Elut; particle size 70-200 μ; mass 7 g) under atmospheric pressure. It was. Fractions containing the product were combined and concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. and then oven-dried under reduced pressure (10 kPa) under about 50 ° C. 0.1 g of 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4,5-dihydrothiazol-2-ylthio) ethyl] pi Ferridine-4-carboxylic acid is obtained in the form of a white solid.
    [3990] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.33 (very broad t, J = 11.5 Hz: 2H); 1.61 (mt: 4H); 1.90 to 2.10 (mt: 4H); 2.45 to 2.60 (mt: 2H); 2.63 (broad d, J = 11.5 Hz: 2H); 3.05 (mt: 2H); 3.19 (t, J = 6.5 Hz: 2H); 3.44 (t, J = 8 Hz: 2H); 3.97 (s: 3 H); 4.15 (t, J = 8 Hz: 2H); 7.35 (broad s: 1H); 7.40 (broad d, J = 9 Hz: 1H); 7.97 (broad d, J = 9 Hz: 1H); 8.69 (broad s: 1H).
    [3991] Ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4,5-dihydrothiazol-2-ylthio) ethyl] piperidine -4-carboxylate
    [3992] Ethyl 1- (2-chloroethyl) -4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate dihydrochloride in 10 cm 3 of dimethylformamide A mixture of 0.7 g, 2-mercaptothiazoline 0.18 g and triethylamine 0.63 cm 3 was stirred at 80 ° C. under an inert atmosphere for 23 hours. After cooling to about 20 ° C., the reaction mixture was poured into water, extracted with ethyl acetate and washed with saturated sodium chloride solution. The organic phase was dried over magnesium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. The evaporation residue was added to a solution of 0.18 g of 2-mercaptothiazoline and 0.06 g of 10% sodium hydride in 10 cm 3 of dimethylformamide, then the mixture was heated to a temperature of 80 ° C. for 15 hours. After cooling to about 20 ° C., the reaction mixture was poured into water, extracted with ethyl acetate and washed with saturated sodium chloride solution. The organic phase was dried over sodium sulfate, filtered and concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. The resulting residue was purified by silica gel column under atmospheric pressure (particle size 70-200 μ; diameter 2cm; 40g weight) dichloromethane / ethanol mixture, eluting with (95/5 by volume basis) is purified by chromatography in a 10-cm 3 Fractions were collected. Fractions 11 to 24 were combined and concentrated to dryness at a temperature of 40 ° C. under reduced pressure (2 kPa). 0.15 g of ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (4,5-dihydrothiazol-2-ylthio) ethyl] Piperidine-4-carboxylate was obtained in the form of a brown oil.
    [3993] 1 H NMR spectrum (300 MHz, CD 3 ) 2 SOd 6 , added a few drops of CF 3 COOD d4, δ (ppm)): 1.06 (t, J = 7 Hz: 3H); 1.41 (mt: 2 H); 1.50 to 1.70 (mt: 4H); 1.98 (broad d, J = 13.5 Hz: 2H); 2.14 (broad t, J = 11.5 Hz: 2H); 2.66 (t, J = 7 Hz: 2H); 2.80 (very broad d, J = 11.5 Hz: 2H); 3.04 (broad t, J = 6.5 Hz: 2H); 3.21 (t, J = 7 Hz: 2H); 3.42 (t, J = 8 Hz: 2H); 3.94 (s: 3 H); 3.97 (q, J = 7 Hz: 2H); 4.12 (t, J = 8 Hz: 2H); 7.32 (d, J = 2.5 Hz: 1H); 7.38 (dd, J = 9 and 2.5 Hz: 1H); 7.96 (d, J = 9 Hz: 1H); 8.66 (d, J = 1.5 Hz: 1H).
    [3994] Ethyl 1- (2-chloroethyl) -4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate dihydrochloride
    [3995] Thionyl chloride 5.73cm 3 dichloromethane 10cm 3 of ethyl 4- [3- (3-fluoro-6-methoxy-quinolin-4-yl) propyl] -1- (2-hydroxyethyl) piperidine- To a suspension of 0.6 g of 4-carboxylate, was added dropwise with stirring at 20 ° C., and the mixture was stirred at a temperature of 20 ° C. for 24 hours. The reaction mixture was concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. The residue was put into cyclohexane 30cm 3 three times and evaporated to dryness under the above conditions. 0.67g ethyl 1- (2-chloroethyl) -4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate dihydrochloride in beige Obtained in the form of a solid.
    [3996] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.05 (t, J = 7 Hz: 3H); 1.45 to 2.00 (mt: 6H); 2.19 (broad d, J = 14 Hz: 2H); 2.75 to 2.95 (mt: 2H); 3.09 (mt: 2 H); 3.40 to 3.60 (mt: 4H); 3.95 to 4.15 (mt: 2H); 3.96 (s: 3 H); 4.05 (q, J = 7 Hz: 2H); 7.37 (d, J = 2.5 Hz: 1 H); 7.42 (dd, J = 9 and 2.5 Hz: 1H); 7.99 (d, J = 9 Hz: 1H); 8.73 (broad s: 1H); 10.00 (unseparated peak: 1H).
    [3997] Ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- (2-hydroxyethyl) piperidine-4-carboxylate was described in Example 46. Prepared in a similar manner.
    [3998] Example 52
    [3999] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenoxy) ethyl] piperidine-4- Carboxylic acid
    [4000] 3-dioxane 50cm, 50cm 3 of methanol and 5N sodium hydroxide solution 4.4cm 3 of ethyl 4- [3- (6-methoxy-quinolin-4-yl 3-fluorophenyl) propyl] -1- [2- (3, A mixture of 0.8 g of 4,5-trifluorophenoxy) ethyl] piperidine-4-carboxylate was stirred at a temperature of 70 ° C. for 18 hours. To the reaction mixture was further added 4.4 cm 3 of 5N aqueous sodium hydroxide solution, which was stirred for 6 hours at a temperature of 70 ° C. After cooling to about 20 ° C., the reaction mixture was concentrated to dryness at a temperature of 50 ° C. under reduced pressure (1.1 kPa). The residue was purified by chromatography eluting with a chloroform / methanol / aqueous ammonia mixture (12/3 / 0.5 by volume) on a column of silica gel (particle size 20-45 μ; diameter 4 cm; height 20 cm) under atmospheric pressure. Fractions 8-19 were combined and concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. and then oven-dried under reduced pressure (10 kPa) under about 50 ° C. 0.59 g of 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenoxy) ethyl] piperidine The 4-carboxylic acid was obtained in the form of a white solid that melts at about 120 ° C.
    [4001] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.32 (very broad t, J = 12 Hz: 2H); 1.59 (mt: 4H); 1.95 (broad d, J = 12 Hz: 2H); 2.07 (broad t, J = 11 Hz: 2H); 2.59 (t, J = 5.5 Hz: 2H); 2.68 (very broad d, J = 11 Hz: 2H); 3.04 (mt: 2 H); 3.95 (s: 3 H); 4.03 (t, J = 5.5 Hz: 2H); 6.97 (mt: 2 H); 7.34 (d, J = 2.5 Hz: 1 H); 7.39 (dd, J = 9 and 2.5 Hz: 1H); 7.96 (d, J = 9 Hz: 1H); 8.69 (broad s: 1H).
    [4002] Ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenoxy) ethyl] piperidine-4 Carboxylate
    [4003] 0.62 g ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate in acetonitrile 80 cm 3 , 0.505 g 5- (2-bromine A mixture of moethoxy) -1,2,3-trifluorobenzene, 0.34 g of potassium iodide and 1.14 g of potassium carbonate was stirred at 70 ° C. under an inert atmosphere for 18 hours. After cooling to about 20 ° C., the suspension was filtered and the insoluble material was washed three times with 30 cm 3 of acetonitrile. The filtrate was concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. The evaporated residue was purified by chromatography eluting with ethyl acetate on a column of silica gel (particle size 20-45 μ; diameter 3 cm; height 21 cm) under atmospheric pressure to collect 40-cm 3 fractions. Fractions 9 to 24 were combined and concentrated to dryness at a temperature of 40 ° C. under reduced pressure (2 kPa). 0.8 g ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,4,5-trifluorophenoxy) ethyl] piperi Dean-4-carboxylate was obtained in the form of a pale yellow viscous oil.
    [4004] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 0.99 (t, J = 7 Hz: 3H); 1.37 (very broad t, J = 12 Hz: 2H); 1.45 to 1.70 (mt: 4H); 1.90 to 2.10 (mt: 4H); 2.59 (t, J = 5.5 Hz: 2H); 2.69 (broad d, J = 12 Hz: 2H); 3.04 (broad t, J = 7Hz: 2H); 3.94 (s: 3 H); 3.97 (q, J = 7 Hz: 2H); 4.03 (t, J = 5.5 Hz: 2H); 6.97 (mt: 2 H); 7.33 (d, J = 2.5 Hz: 1 H); 7.39 (dd, J = 9 and 2.5 Hz: 1H); 7.97 (d, J = 9 Hz: 1 H); 8.69 (broad s: 1H).
    [4005] Ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate was prepared in Example 11.
    [4006] 5- (2-Bromoethoxy) -1,2,3-trifluorobenzene was prepared by applying the method described in Example 13.
    [4007] Example 53
    [4008] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (thiazol-2-ylthio) ethyl] piperidine-4-carboxylic acid
    [4009] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (thiazole-2 in dioxane 3 cm 3 , methanol 3 cm 3 and 5 N aqueous sodium hydroxide solution 1 cm 3 A mixture of 0.15 g of -ylthio) ethyl] piperidine-4-carboxylate was stirred at a temperature of 70 ° C. for 18 hours. After cooling to about 20 ° C., the reaction mixture was concentrated to dryness at a temperature of 50 ° C. under reduced pressure (2 kPa). The residue was placed twice in toluene 20 cm 3 and then concentrated to dryness under the above conditions. The solid was purified by chromatography, eluting with a column of silica gel (Bond Elut; particle size 70-200 μ; mass 7 g) under atmospheric pressure, eluting with a chloroform / methanol / aqueous ammonia mixture (84/14/2 by volume). cm 3 fractions were collected. Fractions 8-19 were combined and concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. and then oven-dried under reduced pressure (10 kPa) under about 50 ° C. 0.114 g of 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (thiazol-2-ylthio) ethyl] piperidine-4-carboxylic acid Was obtained in the form of a white solid.
    [4010] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.31 (broad t, J = 12 Hz: 2H); 1.45 to 1.70 (mt: 4H); 1.90 to 2.10 (mt: 4H); 2.58 (t, J = 7 Hz: 2H); 2.65 (broad d, J = 12 Hz: 2H); 3.04 (mt: 2 H); 3.25 to 3.45 (mt, 2H); 3.95 (s: 3 H); 7.34 (d, J = 2.5 Hz: 1 H); 7.39 (dd, J = 9 and 2.5 Hz: 1H); 7.63 (d, J = 3.5 Hz: 1 H); 7.71 (d, J = 3.5 Hz: 1 H); 7.96 (d, J = 9 Hz: 1H); 8.68 (d, J = 1 Hz: 1 H).
    [4011] Ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (thiazol-2-ylthio) ethyl] piperidine-4-carboxylate
    [4012] Ethyl 1- (2-chloroethyl) -4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate dihydrochloride in acetonitrile 50 cm 3 0.65 g, a mixture of 0.183 g of 2-mercaptothiazole, 0.21 g of potassium iodide and 0.88 g of potassium carbonate was stirred for 18 hours under an inert atmosphere at a temperature of 70 ° C. After cooling to about 20 ° C., the suspension was filtered and the insoluble material was washed with acetonitrile. The filtrate was concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. The evaporation residue was placed in a mixture of ethyl acetate / 40-60 ° C. petroleum ether (8/2 on a volume basis), filtered and the filtrate under atmospheric pressure on a column of silica gel (particle size 70-200 μ; diameter 1.5 cm; Mass, 100 g), purified by chromatography, eluting with ethyl acetate / 40-60 ° C. petroleum ether (8/2 by volume) to collect 15-cm 3 fractions. Fractions 41 to 100 were combined and concentrated to dryness at a temperature of 40 ° C. under reduced pressure (2 kPa). 0.15 g of ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (thiazol-2-ylthio) ethyl] piperidine-4- Carboxylate was obtained in the form of a dark yellow oil.
    [4013] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.00 (t, J = 7 Hz: 3H); 1.36 (broad t, J = 11.5 Hz: 2H); 1.45 to 1.70 (mt: 4H); 1.85 to 2.10 (mt: 4H); 2.59 (t, J = 7 Hz: 2H); 2.68 (broad d, J = 12 Hz: 2H); 3.05 (very broad t, J = 7 Hz: 2H); 3.33 (mt: 2 H); 3.96 (s: 3 H); 3.98 (q, J = 7 Hz: 2H); 7.35 (d, J = 2.5 Hz: 1H); 7.40 (dd, J = 9 and 2.5 Hz: 1H); 7.64 (d, J = 3.5 Hz: 1 H); 7.72 (d, J = 3.5 Hz: 1 H); 7.97 (d, J = 9 Hz: 1 H); 8.70 (d, J = 1 Hz: 1H).
    [4014] Ethyl 1- (2-chloroethyl) -4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate dihydrochloride was prepared in Example 51. It was.
    [4015] Example 54
    [4016] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- (3-phenylaryl) piperidine-4-carboxylic acid
    [4017] Dioxane 2cm 3, 2cm 3 of methanol and 5N sodium hydroxide aqueous solution 1.32cm 3 of ethyl 4- [3- (3-fluoro-6-methoxy-quinolin-4-yl) propyl] -1- (3-phenyl-allyl) A mixture of 0.13 g of piperidine-4-carboxylate was stirred at a temperature of 70 ° C. for 18 hours. After cooling to about 20 ° C., the reaction mixture was concentrated to dryness at a temperature of 50 ° C. under reduced pressure (2 kPa). The residue was poured into 10 cm 3 of water, acidified with acetic acid, extracted with ethyl acetate, separated by sedimentation, filtered, and washed twice with 10 cm 3 of ethanol. White solid which melts 0.12 g of 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- (3-phenylallyl) piperidine-4-carboxylic acid at 240 ° C Obtained in the form of.
    [4018] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.35 (broad t, J = 11.5 Hz: 2H); 1.50 to 1.75 (mt: 4H); 1.85 to 2.10 (mt: 4H); 2.63 (broad d, J = 11.5 Hz: 2H); 2.95 to 3.15 (mt: 4H); 3.96 (s, 3 H); 6.26 (dt, J = 16 and 7 Hz: 1H); 6.50 (d, J = 16 Hz: 1H); 7.10 to 7.50 (mt: 7H); 8.06 (d, J = 9 Hz: 1H ); 8.69 (broad s: 1H).
    [4019] Ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- (3-phenylaryl) piperidine-4-carboxylate
    [4020] Ethanol 10cm 3 of ethyl 4- [3- (3-fluoro-6-methoxy-quinolin-4-yl) propyl] piperidine-4-carboxylate 0.31g and the trans-borane To a mixture of cinnamaldehyde 0.1cm 3 77 mg of pyridine complex was added. The reaction mixture was maintained at a temperature of 77 ° C. for 22 hours. After cooling to about 20 ° C, the reaction mixture was concentrated to dryness under reduced pressure (2 kPa) at a temperature of 40 ° C. The obtained residue was poured into 10 cm 3 of water, extracted twice with 10 cm 3 of dichloromethane, dried over magnesium sulfate, filtered, and concentrated to dryness under the above conditions. The residue obtained was subjected to an ethyl acetate / cyclohexane mixture (40/60 on a volume basis), followed by a dichloromethane / methanol mixture in a column of silica gel (particle size 70-200 μ; diameter 2.5 cm; mass 20 g) under a pressure of 60 kPa argon. Chromatography eluting at (95/5 by volume). Fractions containing the expected product were combined and concentrated to dryness under the above conditions. 0.13 g of ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- (3-phenylallyl) piperidine-4-carboxylate in the form of a viscous oil It was.
    [4021] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.01 (t, J = 7 Hz: 3H); 1.40 (broad t, J = 11.5 Hz: 2H); 1.45 to 1.75 (mt: 4H); 1.90 to 2.05 (mt: 4H); 2.65 (very broad d, J = 12 Hz: 2H); 3.02 (d, J = 7 Hz: 2H); 3.05 (mt: 2H); 3.96 (s: 3 H); 3.97 (q, J = 7 Hz: 2H); 6.25 (dt, J = 16 and 7 Hz: 1H); 6.51 (d, J = 16 Hz: 1H); 7.15 to 7.50 (mt: 7H); 7.96 (d, J = 9 Hz: 1H); 8.70 (d, J = 1 Hz: 1H).
    [4022] Ethyl 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylate was prepared in Example 11.
    [4023] Example 55
    [4024] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl) piperidine-4-hydroxysamic acid
    [4025] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl) piperidine-4-tert-butoxycar in 2 cm 3 of trifluoroacetic acid A solution of 0.1 g of radiamide is left at 60 ° C. for 60 days. The solution was evaporated under reduced pressure (2 kPa) at a temperature of 40 ° C. and then under atmospheric pressure in a mixture of dichloromethane / methanol / aqueous ammonia in Bond Elut silica (particle size 70-200 μ; volume 25 cm 3 ) (volume 40/5 / 0.3 Purification was carried out by chromatography, eluting with). Fractions containing product were combined and evaporated under the above conditions. 0.036 g of 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl) piperidine-4-hydroxysamic acid is obtained in the form of a colorless oil. It was.
    [4026] ' H NMR Spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.33 (mt: 2H); 1.51 (mt: 2 H); 1.60 to 1.80 (mt: 4H); 1.90 to 2.10 (mt: 4H); 2.18 (t, J = 7 Hz: 2H); 2.45 to 2.65 (mt: 4H); 3.12 (broad t, J = 7.5 Hz: 2H); 3.96 (s: 3 H); 7.15 to 7.25 (mt: 3H); 7.28 (t mt, J = 7.5 Hz: 2H); 7.36 (d, J = 2.5 Hz: 1 H); 7.45 (dd, J = 9 and 2.5 Hz: 1H); 7.96 (d, J = 9 Hz: 1H); 8.56 (unisolated peak: 1H); 8.67 (s: 1 H); 10.37 (unisolated peak: 1H).
    [4027] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl) piperidine-4-tert-butoxyamide
    [4028] 0.5 g of 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl) piperidine-4-carboxylic acid, 1-hydroxy-benzotriazole hydrate A mixture of 0.175 g, 0.498 g of 1- [3- (dimethylamino) -propyl] -3-ethylcarbodiimide hydrochloride, 0.58 cm 3 of triethylamine and 0.4 g of O-tert-butylhydroxyamine was subjected to 20 ° C. Stirred at a temperature of 48 hours. The reaction medium was diluted with 50 cm 3 of water, stirred and the phases separated by sedimentation. The aqueous phase was extracted twice with 25 cm 3 of dichloromethane and the organic extracts combined, dried over magnesium sulfate, filtered and evaporated under reduced pressure (2 kPa) at a temperature of 40 ° C. The obtained residue was chromatographed under atmospheric pressure, eluting with a dichloromethane / methanol / aqueous ammonia mixture (40/5 / 0.2 by volume) in a column of silica gel (particle size 20-45 μ; diameter 2.5 cm; mass 18 g). Purified. Fractions containing product were combined and evaporated under the above conditions. 0.27 g of 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl) piperidine-4-tert-butoxyamide were obtained.
    [4029] ' H NMR Spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.09 (s: 9H); 1.35 (mt: 2 H); 1.54 (mt: 2 H); 1.67 (mt: 4H); 1.95 (broad t, J = 11 Hz: 2H); 2.08 (broad d, J = 13.5 Hz: 2H); 2.19 (t, J = 7 Hz: 2H); 2.50 to 2.65 (mt: 4H); 3.14 (broad t, J = 7.5 Hz: 2H); 3.98 (s: 3 H); 7.10 to 7.25 (mt: 3H); 7.27 (broad t, J = 7.5 Hz: 2H); 7.36 (d, J = 2.5 Hz: 1 H); 7.45 (dd, J = 9 and 2.5 Hz: 1H); 7.96 (d, J = 9 Hz: 1H); 8.68 (s: 1 H); 10.06 (broad s: 1H).
    [4030] 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl) piperidine-4-carboxylic acid dihydrochloride was prepared in Example 4.
    [4031] Benzyl 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- (3-phenylpropyl) piperidine-4-carboxylate was prepared in Example 4.
    [4032] Example 56
    [4033] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,5-difluorophenyl) prop-2-enyl] piperidine- 4-carboxylic acid hydrochloride
    [4034] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [3- (2,5-difluorophenyl), according to the method analogous to that of Example 54 Prop-2-enyl] piperidine-4-carboxylic acid hydrochloride was prepared.
    [4035] 1 H NMR spectrum (CD 3 ) 2 SO-d 6 , δ (ppm) dropwise adding CD 3 COOD-d 4 as a small drop at a temperature of 400 MHz, 383 K: 1.73 (mt: 6H); 2.22 (broad d, J = 14 Hz: 2H); 3.01 (unisolated peak: 2H); 3.11 (broad t, J = 7Hz: 2H); 3.42 (very broad d, J = 12 Hz: 2H); 3.94 (d, J = 7 Hz: 2H); 3.98 (s: 3 H); 6.48 (dt, J = 16.5 and 7 Hz: 1H); 6.93 (d, J = 16.5 Hz: 1 H); 7.10 to 7.30 (mt: 2H); 7.35 (broad s: 1H); 7.40 (dd, J = 9 and 2.5 Hz: 1H); 7.44 (mt: 1 H); 7.98 (d, J = 9 Hz: 1 H); 8.64 (broad s: 1H).
    [4036] Example 57
    [4037] 4- [3- (3-fluoro-6-methoxyquinolin-yl) propyl] -1- [2- (2,5-difluorophenoxy) ethyl] piperidine-4-hydroxysamic acid
    [4038] 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- [2- (2,5-difluorophenoxy, according to a method analogous to that of Example 55 ) Ethyl] piperidine-4-hydroxysamic acid was prepared.
    [4039] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.31 (very broad t, J = 12.5 Hz: 2H); 1.45 to 1.70 (mt: 4H); 2.02 (broad d, J = 12.5 Hz: 2H); 2.10 (broad t, J = 11 Hz: 2H); 2.55 to 2.75 (mt: 4H); 3.00 (mt: 2 H); 3.97 (s: 3 H); 4.12 (t, J = 5.5 Hz: 2H); 6.75 (mt: 1 H); 7.14 (mt: 1 H) 7.24 (mt: 1 H); 7.33 (d, J = 3 Hz: 1 H); 7.40 (dd, J = 9 and 3 Hz: 1H); 7.96 (d, J = 9 Hz: 1H); 8.63 (unisolated peak: 1H); 8.70 (d, J = 0.5 Hz: 1H); 10.40 (unisolated peak: 1H).
    [4040] Example 58
    [4041] 1-cinamyl-4- [3- (3-fluoro-6-methoxyquinolin-yl) propyl] -piperidine-4-hydroxysamic acid
    [4042] According to a method analogous to that of Example 55, 1-cinnamyl-4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-hydroxysamic acid was prepared. .
    [4043] 1 H NMR spectrum (400 MHz, addition of a few drops of CD 3 COOD-d 4 at 373K (CD 3 ) 2 SO-d 6 , δ (ppm)): 1.50 to 1.75 (mt: 6H); 2.23 (broad d, J = 14 Hz: 2H); 2.81 (broad t, J = 11.5 Hz: 2H); 3.04 (mt: 2 H); 3.22 (broad d, J = 11.5 Hz: 2H); 3.69 (d, J = 7 Hz: 2H); 3.97 (s: 3 H); 6.24 (dt, J = 16 and 7 Hz: 1H); 6.78 (d, J = 16 Hz: 1H); 7.20 to 7.50 (mt: 7H); 7.96 (d, J = 9 Hz: 1H); 8.62 (broad s: 1H).
    [4044] Example 59
    [4045] Sodium 4- [3- (3-chloro-6-trifluoromethylquinolin-4-yl) propyl] -1- [2- (2,5-difluorophenoxy) ethyl] piperidine-4- Carboxylate
    [4046] Sodium 4- [3- (3-chloro-6-trifluoromethoxyquinolin-4-yl) propyl] -1- [2- (2,5-difluoro) according to a method analogous to that of Example 1 Phenoxy) ethyl] piperidine-4-carboxylate was prepared.
    [4047] 1 H NMR spectrum (300 MHz, (CD 3 ) 2 SO-d 6 , δ (ppm)):
    [4048] 1.09 (very broad t, J = 11.5 Hz: 2H); 1.40 to 1.70 (mt: 4H); 1.98 (broad d, J = 11.5 Hz: 2H); 2.14 (t, J = 10.5 Hz: 2H); 2.50 to 2.70 (mt: 4H); 3.22 (broad t, J = 7Hz: 2H); 4.10 (t, J = 5.5 Hz: 2H); 6.74 (mt: 1 H); 7.12 (mt: 1 H); 7.23 (mt: 1 H); 8.06 (broad d, J = 9 Hz: 1H); 8.26 (d, J = 9 Hz: 1 H); 8.26 (d, J = 9 Hz: 1 H); 8.54 (broad s: 1H); 9.00 (s: 1 H).
    [4049] The present invention comprises one or more heterocyclylalkyl piperidine derivatives according to the invention, if necessary, in salt form, in pure form or in combination with one or more compatible and pharmaceutically acceptable diluents and / or adjuvants. It relates to a pharmaceutical composition.
    [4050] The compositions of the present invention can be used orally, orally, topically, rectally or aerosols.
    [4051] Solid compositions for oral administration that can be used include tablets, pills, gels, capsules, powders or granules. In these compositions, the active compounds of the present invention are mixed with one or more inert diluents or auxiliaries, for example sucrose, lactose or starch. These compositions may include, in addition to the diluent, other materials, for example lubricants such as magnesium stearate or coatings for controlled release.
    [4052] Liquid compositions for oral administration that can be used include pharmaceutically acceptable solutions, suspensions, emulsions, syrups and elisers containing inert diluents such as water or liquid paraffin. These compositions may also include, for example, wetting agents, sweeteners or flavoring agents as substances other than diluents.
    [4053] Compositions for parenteral administration may be sterile liquids or emulsions. Solvents or vehicles that can be used include water, propylene glycol, polyethylene glycol, vegetable oils, in particular olive oil and injectable organic esters such as ethyl oleate. These compositions may also contain auxiliaries, in particular wetting agents, isotonic agents, emulsifiers, suspending agents and stabilizers.
    [4054] Sterilization can be carried out in several ways, for example by using, irradiating or heating a sterile filter. The compositions of the invention can also be prepared in the form of sterile solid compositions, which can be dissolved at the time of use in sterile water or other sterile injectable media.
    [4055] Compositions for topical administration can be, for example, creams, ointments, lotions or aerosols.
    [4056] Compositions for rectal administration are suppositories or rectal capsules, which contain, in addition to the active substance, excipients such as cocoa butter, semi-synthetic glycerides or polyethylene glycols.
    [4057] The composition of the present invention may also be an aerosol. When used in the form of a liquid aerosol, the composition may be a solid sterile solution or a solid composition that dissolves at the time of use in non-pyrogenic sterile water, saline or other pharmaceutically acceptable vehicles. When used in the form of anhydrous aerosols to be inhaled directly, the active substance is ground and combined with a water soluble solid diluent or vehicle, for example dextran, mannitol or lactose, having a particle size of 30 to 80 μm.
    [4058] In the treatment of humans, the novel heterocyclylalkyl piperidine derivatives according to the invention are particularly advantageous for treating infections of bacterial origin. Dosage depends on the desired effect and duration of treatment. The physician will be able to determine the most appropriate dose based on age, weight, extent of infection and other factors specific to the patient being treated as a treatment function. Generally, the dose is from 750 mg to 3 g of active ingredient 2 or 3 times daily orally for adults or 400 mg to 1.2 g for intravenous administration.
    权利要求:
    Claims (12)
    [1" claim-type="Currently amended] A heterocyclylalkyl piperidine derivative of formula (I), an enantiomer thereof, a diastereomer thereof or a mixture thereof and / or, if necessary, a syn or anti form thereof, a mixture thereof or a salt thereof.
    Formula I

    In the above formula,
    X 1 , X 2 , X 3 , X 4 and X 5 each represent> C—R ′ 1 to> C—R ′ 5 , or optionally only one of them represents a nitrogen atom,
    R 1 , R ' 1 , R' 2 , R ' 3 , R' 4 and R ' 5 are the same or different and represent a hydrogen or halogen atom, or are alkyl, cycloalkyl, phenyl, phenylthio, mono- or bicy Click aromatic heterocyclyl or heterocyclylthio, hydroxyl, alkyloxy, trifluoromethoxy, alkylthio, trifluoromethylthio, cycloalkyloxy, cycloalkylthio, cyano, carboxyl, alkyloxycarbonyl, cyclo Alkyloxycarbonyl, -NRaRb or -CONRaRb radicals wherein Ra and Rb are hydrogen, alkyl, cycloalkyl, phenyl, mono- or bicyclic aromatic heterocyclyl or Ra and Rb together with the nitrogen atom to which they are attached May optionally contain other heteroatoms selected from O, S and N, and if necessary a nitrogen atom or, if necessary, a sulfur atom, wherein the sulfur atom is oxidized in the form of sulfinyl or sulfonyl Form a 5- or 6-membered heterocycle containing alkyl, phenyl or mono- or bicyclic aromatic heterocyclyl substituents; or fluoro, hydroxyl, alkyloxy, alkylthio, cycloalkyloxy , Cycloalkylthio, phenyl, mono- or bicyclic aromatic heterocyclyl, carboxyl, alkyloxycarbonyl, cycloalkyloxycarbonyl, -NRaRb or -CONRaRb, where Ra and Rb are as defined above Represents substituted methylene, phenoxy, heterocyclyloxy, benzyloxy, heterocyclylmethyloxy, or optionally R 1 is also difluoromethoxy or -C m F 2m + 1 , -SC m F 2 m + 1 or OC m F 2 m + 1 , wherein m is an integer from 1 to 6, or optionally R ' 5 may also represent trifluoroacetyl,
    R 2 represents carboxyl, alkyloxycarbonyl, cycloalkoxycarbonyl, cyano, -CONRaRb, wherein Ra and Rb each represent hydrogen, alkyl, cycloalkyl, phenyl, mono- or bicyclic aromatic heterocyclyl , Ra or Rb represents hydroxyl, alkyloxy or cycloalkyloxy, or Ra and Rb together with the nitrogen atom to which they are bound may contain other heteroatoms optionally selected from O, S and N, 5-membered containing alkyl, phenyl or mono- or bicyclic aromatic heterocyclyl substituents at a nitrogen atom or, if necessary, a sulfur atom, wherein the sulfur atom is oxidized in the form of sulfinyl or sulfonyl; or 6 indicate the won to form a heterocycle; or, R 2 is hydroxymethyl, containing 1 or 2 carbon atoms substituted by alkyl carboxyl, alkyloxycarbonyl, Inc. Claw alkyloxycarbonyl, cyano or -CONRaRb represent (wherein, Ra and Rb are the same as defined above), or, R 2 is -CF 2 -Rc, -C (CH 3 ) 2 -Rc, -CO-Rc Radicals of -CHOH-Rc, -C (cycloalkyl) -Rc or -CH = CH-Rc, wherein Rc is carboxyl, alkyloxycarbonyl, cycloalkyloxycarbonyl or -CONRaRb where Ra and Rb are As defined above),
    R 3 is a phenyl, mono- or bicyclic aromatic heterocyclyl or alk-R o 3 radical, where alk is an alkyl radical and R o 3 is hydrogen, halogen, hydroxyl, alkyloxy, alkylthio, alkylsulphi Nyl, alkylsulfonyl, alkylamino, dialkylamino, cycloalkyl, cycloalkyloxy, cycloalkylthio, cycloalkylsulfinyl, cycloalkylsulfonyl, cycloalkylamino, N-cycloalkyl-N-alkylamino, -N -(Cycloalkyl) 2 , acyl, cycloalkylcarbonyl, phenyl, phenoxy, phenylthio, phenylsulfinyl, phenylsulfonyl, phenylamino, N-alkyl-N-phenylamino, N-cycloalkyl-N-phenyl Amino, -N- (phenyl) 2 , phenylalkyloxy, phenylacylthio, phenylalkylsulfinyl, phenylalkylsulfonyl, phenylalkylamino, N-alkyl-N-phenylaminoalkyl, N-cycloalkyl-N-phenyl Alkylamino, benzoyl, mono- or bicyclic aromatic heterocyclyl, he Rocyclyloxy, heterocyclylthio, heterocyclylsulfinyl, heterocyclylsulfonyl, heterocyclylamino, N-alkyl-N-heterocyclylamino, N-cycloalkyl-N-heterocyclylamino, hetero Cyclylcarbonyl, heterocyclylalkyloxy, heterocyclylalkylthio, heterocyclylalkylsulfinyl, heterocyclylalkylsulfonyl, heterocyclylalkylamino, N-alkyl-N-heterocyclylaminoalkyl, N -Cycloalkyl-N-heterocyclylaminoalkyl, wherein the heterocyclyl moiety mentioned above is mono- or bicyclic aromatic, carboxyl, alkyloxycarbonyl, -NRaRb or -CO-NRaRb, wherein Ra and Rb is as defined in the definition of R 2 ), or optionally R o 3 is -CR'b = CR'c-R'a, where R'a is phenyl, phenylalkyl, heterocyclyl or hetero Cyclylalkyl, where heterocyclyl moiety Minutes are mono- or bicyclic aromatic), phenoxyalkyl, phenylthioalkyl, phenylsulfinylalkyl, phenylsulfonylalkyl, phenylaminoalkyl, N-alkyl-N-phenylaminoalkyl, heterocyclyloxyalkyl, Heterocyclylthioalkyl, heterocyclylsulfinylalkyl, heterocyclylsulfonylalkyl, heterocyclylaminoalkyl, N-alkyl-N-heterocyclylaminoalkyl, heterocyclylthio, heterocyclylsulfinyl, heterocycle Arylsulfonyl (the heterocyclyl moiety mentioned above is mono- or bicyclic aromatic), phenylthio, phenylsulfinyl, phenylsulfonyl, R'b and R'c represent hydrogen, alkyl or cycloalkyl Or optionally R o 3 represents a radical -C≡C-Rd wherein Rd is alkyl, phenyl, phenylalkyl, phenoxyalkyl, phenylthioalkyl, N-alkyl-N-phenylaminoalkyl, mono -Or bicyclic aromatic he Cyclyl, heterocyclylalkyl, heterocyclyloxyalkyl, heterocyclylthioalkyl, heterocyclylaminoalkyl, N-alkyl-N-heterocyclylaminoalkyl (heterocyclyl moieties mentioned above are mono -Or bicyclic aromatic), or optionally R o 3 represents -CF 2 -phenyl or mono- or bicyclic aromatic -CF 2 -heterocyclyl radical,
    Y is a radical> CH-Re, wherein Re is hydrogen, fluoro, hydroxyl, alkyloxy, cycloalkyloxy, carboxyl, alkyloxycarbonyl, cycloalkyloxycarbonyl, -NRaRb or -CO-NRaRb [where Ra and Rb are as defined in the definition of R 2 , or one is a hydrogen atom and the other is an alkyloxycarbonyl, acyl, cycloalkylcarbonyl, benzoyl or heterocyclylcarbonyl radical, wherein the heterocyclyl moiety is Mono- or bicyclic aromatic), or optionally Y is difluoromethylene, carbonyl, hydroxyliminomethylene, alkyloxyiminomethylene or cycloalkyl containing from 3 to 6 carbon atoms. Oxyiminomethylene radical or 1,1-cycloalkylene radical,
    n is an integer of 0 to 4,
    The phenyl, benzyl, benzoyl or heterocyclyl radicals or moieties mentioned above may be optionally substituted with halogen, hydroxyl, alkyl, alkyloxy, alkyloxyalkyl, haloalkyl, trifluoromethyl, trifluoromethoxy, trifluoromethylthio Selected from carboxyl, alkyloxycarbonyl, cyano, alkylamino, -NRaRb, wherein Ra and Rb are as defined above, phenyl, hydroxyalkyl, alkylthioalkyl, alkylsulfinylalkyl and alkylsulfonylalkyl 1 to 4 substituents, where alkyl or acyl radicals and moieties contain 1 to 10 carbon atoms in the straight or branched chain (except where specifically noted), and cycloalkyl radicals contain 3 to 6 carbon atoms Is understood to be substituted by the
    [2" claim-type="Currently amended] The compound of claim 1 , wherein X 1 , X 2 , X 3 , X 4 and X 5 each represent> C—R ′ 1 to> C—R ′ 5 , or optionally only one of them represents a nitrogen atom,
    Methylene radicals wherein R 1 , R ' 1 , R' 2 , R ' 3 , R' 4 and R ' 5 are the same or different and represent a hydrogen or halogen atom or represent an alkyl or alkyloxy radical or substituted by alkyloxy Indicates
    R 2 represents carboxyl, alkyloxycarbonyl or —CONRaRb, wherein Ra represents a hydrogen atom and Rb represents a hydrogen atom or a hydroxyl radical, or
    R 2 represents hydroxymethyl, alkyl or alkyloxycarbonyl containing 1 or 2 carbon atoms substituted by carboxyl,
    R 3 is a radical alk-R o 3 where alk represents an alkyl radical and R o 3 represents hydrogen, cycloalkyl, cycloalkylthio, phenyl, phenoxy, phenylthio, phenylamino, heterocyclyloxy or heterocycle Arylthio, or optionally R o 3 represents -CR'b = CR'c-R'a, wherein R'a represents phenyl and R'b and R'c represent hydrogen;
    Y represents the radical> CH-Re, where Re is hydrogen, fluoro or hydroxyl,
    n is an integer of 2 to 3,
    The phenyl or heterocyclyl radicals or moieties mentioned above may be optionally substituted with 1 to 4 halogens in the ring, and the alkyl or acyl radicals and moieties may be 1 to 10 linear or branched (except where specifically noted). A cycloalkyl radical containing a carbon atom, the cycloalkyl radical containing 3 to 6 carbon atoms, an enantiomer thereof, a diastereomer thereof or a mixture thereof and / or syn Or in anti form, mixtures thereof or salts thereof.
    [3" claim-type="Currently amended] The compound of claim 1, wherein 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (thien-2-yl) thioethyl] piperidine-4- Heterocyclylalkyl piperidine derivatives, characterized in that they are carboxylic acids or salts thereof.
    [4" claim-type="Currently amended] The compound of claim 1, wherein 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2- (3,5-difluorophenoxy) ethyl] piperidine Heterocyclylalkyl piperidine derivatives, characterized in that they are -4-carboxylic acids or salts thereof.
    [5" claim-type="Currently amended] The compound of claim 1, wherein 4- [3- (3-chloro-6-methoxyquinolin-4-yl) propyl] -1- [2-thiazole-2-thioethyl) piperidine-4-carboxylic acid or Heterocyclylalkyl piperidine derivatives, characterized in that salts thereof.
    [6" claim-type="Currently amended] The compound according to claim 1, wherein 1- (2-cyclopentylthioethyl) -4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] piperidine-4-carboxylic acid or salt thereof Heterocyclylalkyl piperidine derivatives characterized in that.
    [7" claim-type="Currently amended] The compound according to claim 1, which is 4- [3- (3-fluoro-6-methoxyquinolin-4-yl) propyl] -1- (3-phenylallyl) piperidine-4-carboxylic acid or a salt thereof. Heterocyclylalkyl piperidine derivative | guide_body.
    [8" claim-type="Currently amended] The chain R 3 as defined in claim 1 is then coupled with a heterocyclylalkyl piperidine derivative of formula II, optionally removing acid protecting or amine protecting radicals, and optionally separating enantiomeric or diastereomeric forms. And / or, if necessary, syn or anti-separation, and optionally the product obtained is converted to a salt, the process for preparing the heterocyclylalkyl piperidine derivative as claimed in claim 1.
    Formula II

    In the above formula,
    X 1 , X 2 , X 3 , X 4 , X 5 , R 1 , R 2 , Y and n are as defined above,
    R 2 is protected when it has a carboxyl or amino radical.
    [9" claim-type="Currently amended] The method of claim 8, wherein the linkage of the chain R 3 to piperidine is performed by reacting a derivative of the formula:
    R 3 -X
    In the above formula,
    R 3 is as defined above,
    X represents a halogen atom, a methylsulfonyl radical, a trifluoromethylsulfonyl radical or a p-toluenesulfonyl radical.
    [10" claim-type="Currently amended] The compound of claim 8 or 9, wherein R 3 represents a radical -alk-R o 3 wherein alk represents an alkyl radical and R o 3 represents -C≡C-Rd wherein Rd is phenyl, phenylalkyl, Heterocyclyl or mono- or bicyclic aromatic heterocyclylalkyl), alkynyl halide: HC≡C-alk-X, where alk is as defined above and X is a halogen atom. ) And then the chain is replaced by a phenyl, phenylalkyl, heterocyclyl or heterocyclylalkyl radical to carry out the reaction.
    [11" claim-type="Currently amended] The compound of claim 8 or 9, wherein R 3 represents a radical -alk-R o 3 wherein alk represents an alkyl radical and R o 3 represents phenoxy, phenylthio, phenylamino, heterocyclyloxy, heterocycle. Arylthio or heterocyclylamino radicals, wherein the heterocyclyl moiety is aromatic], first condensed the chain HO-alk-X, where X is a halogen atom, and then the hydroxy obtained Convert the alkyl chain to a haloalkyl, methanesulfonylalkyl or p-toluenesulfonylalkyl chain, and finally in the basic medium an aromatic derivative of Ar-ZH, wherein Ar is a phenyl or aromatic heterocyclyl radical, and Z is sulfur , Oxygen or nitrogen atom).
    [12" claim-type="Currently amended] A pharmaceutical composition comprising one or more derivatives as claimed in claim 1 in pure form or in combination with one or more miscible and pharmaceutically acceptable diluents and / or adjuvants.
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    同族专利:
    公开号 | 公开日
    KR100849608B1|2008-07-31|
    SK5822003A3|2004-06-08|
    PL363004A1|2004-11-15|
    JP2004514661A|2004-05-20|
    YU46803A|2006-05-25|
    WO2002040474A2|2002-05-23|
    BG107793A|2004-08-31|
    ZA200303794B|2004-06-29|
    EP1695964A1|2006-08-30|
    HU0303758A3|2009-08-28|
    AU1836502A|2002-05-27|
    BR0115312A|2003-09-23|
    DE60122567D1|2006-10-05|
    PT1337529E|2006-12-29|
    CZ20031316A3|2003-10-15|
    ES2271119T3|2007-04-16|
    EA200300568A1|2003-12-25|
    IL155841D0|2003-12-23|
    FR2816618B1|2002-12-27|
    NO20032187D0|2003-05-14|
    CN1483031A|2004-03-17|
    DK1337529T3|2006-12-18|
    EP1337529A2|2003-08-27|
    CA2429311A1|2002-05-23|
    AU2002218365B2|2007-07-05|
    NO20072142L|2007-04-25|
    AR034006A1|2004-01-21|
    AT337311T|2006-09-15|
    WO2002040474A3|2002-10-31|
    FR2816618A1|2002-05-17|
    EE200300207A|2003-08-15|
    EP1337529B1|2006-08-23|
    DE60122567T2|2007-08-23|
    HRP20030379A2|2005-04-30|
    HU0303758A2|2004-03-01|
    NO20032187L|2003-06-26|
    TNSN01160A1|2005-11-10|
    引用文献:
    公开号 | 申请日 | 公开日 | 申请人 | 专利标题
    法律状态:
    2000-11-15|Priority to FR0014738A
    2000-11-15|Priority to FR00/14738
    2001-11-14|Application filed by 아방티 파르마 소시에테 아노님
    2001-11-14|Priority to PCT/FR2001/003559
    2003-07-16|Publication of KR20030060934A
    2008-07-31|Application granted
    2008-07-31|Publication of KR100849608B1
    优先权:
    申请号 | 申请日 | 专利标题
    FR0014738A|FR2816618B1|2000-11-15|2000-11-15|Heterocyclylalcoyl piperidine derivatives, their preparation and the compositions containing them|
    FR00/14738|2000-11-15|
    PCT/FR2001/003559|WO2002040474A2|2000-11-15|2001-11-14|Heterocyclylalkyl piperidine derivatives and their use as antimicrobial agents|
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