Fused thiophene derivatives and drugs containing the same as the active ingredient

专利摘要:
The present invention relates to an interleukin-6 and / or an interleukin-12-production inhibitor containing a condensed thiophene derivative represented by the formula (I) and a derivative thereof as an active ingredient (the symbols in the formula are as described in the specification). The condensed thiophene derivatives represented by formula (I) are useful for the treatment of various inflammatory diseases, sepsis, multiple myeloma, plasma cell leukemia, osteoporosis, cachexia, psoriasis, nephritis, renal cell carcinoma, Kaposi sarcoma, chronic arthritic rheumatism, hypergammaglobulinemia, , Atrial myxoma, diabetes, autoimmune diseases, hepatitis, multiple sclerosis, colitis, graft-versus-host disease, and infectious diseases.
公开号:KR20020009383A
申请号:KR1020007010843
申请日:1999-03-31
公开日:2002-02-01
发明作者:고니시미키오；가츠베노부오；곤노미토시；기시모토다다미츠
申请人:우에노 도시오；오노 야꾸힝 고교 가부시키가이샤；
IPC主号:

专利说明:

FIELD OF THE INVENTION The present invention relates to a pharmaceutical composition containing a thiophene derivative and a derivative thereof,
[6] Cytokines are multifunctional factors that play an important role in biological defense mechanisms and are deeply involved in various life phenomena. However, there are many examples of diseases that are thought to be caused by their overproduction or their overreaction.
[7] IL-6 is a cytokine produced by various cells such as T cells, B cells, macrophages, Shinmeganum gum (renal mesangium) cells and fibroblasts. It induces differentiation of B cells into antibody producing cells, activation of T cells , Induction of platelet increase, induction of acute phase protein production from hepatocytes, and so on. However, abnormal IL-6 production is observed in various inflammation, autoimmune and tumorigenic diseases, suggesting that it plays a role in hospitals of these diseases. In addition, various pathological conditions are reproduced in an experiment using a model animal in which IL-6 is forcibly expressed, and the relation between IL-6 production abnormality and disease is stronger ( Biochem. J. , 265 , 621 (1990), Immunol . Today, 11, 443 (1990 ), J. Autoimmun., 5 Suppl A, 123 (1992), see Clin. Immunol. Immunopathol., 62 , S60 (1992)).
[8] IL-12 is a cytokine produced from cells such as macrophages and dendritic cells, and is a cytokine that activates natural killer (hereinafter referred to as NK) cells, interferon-γ from NK cells and T cells (hereinafter referred to as IFN- And the balance control of Th1 and Th2. Helper T cells are divided into Th1 promoting cellular immunity and Th2 promoting liquid immunity, but IL-12 acts as a Th1 inducer from helper T cell progenitor cells. IL-12 acts as a central cytokine that induces an inflammatory immune response leading to long-term injury through the action of inducing IFN-y production of further differentiated Th1 cells and enhancing killer activity (See Blood , 84 , 4008 (1994)).
[9] Therefore, an improvement effect on various conditions represented by inflammatory diseases is expected by inhibiting the production of IL-6 and / or IL-12. The present invention is to provide novel cytotoxic drugs by inhibiting the production of these cytokines.
[10] Clinical applications of the compounds used in the present invention may be directed to diseases in which the production of IL-6 and / or IL-12, or an over-reaction to them, . Examples of IL-6 production inhibitors include various inflammatory diseases, sepsis, multiple myeloma, plasma cell leukemia, osteoporosis, cachexia, psoriasis, nephritis, renal cell carcinoma, Kaposi sarcoma, chronic arthritic rheumatism, hypergammaglobulinemia, ( J. Immunol. , 145 , 4185 (1990), J. Exp. Med. , 172 , 1505 (1990), J. Clin. Invest ., 87, 739 (1991) , J. Clin. Invest., 89, 1681 (1992), EMBO J., 13, 1189 (1994),. Hematol. Oncol. Clin. North Am, 11, 159 (1997) Reference). In addition, there may be mentioned as the production of IL-12 inhibitors, such as various inflammatory diseases, diabetes, hepatitis, multiple sclerosis, colitis, graft pair host disease, chronic rheumatoid arthritis, infectious diseases, the prevention and / or treatment of autoimmune diseases (J. Exp . Med., 181, 817 ( 1995), J. Exp. Med., 181, 381 (1995), J. Exp. Med., 182, 1281 (1995), Ann, NY Acad. Sci., 795, 371 (1996), Int. Immunol. , 8 , 569 (1996), Proc. Natl. Acad. Sci. USA , 92 , 4823 (1996)).
[11] Further, the compound represented by the formula (XI) is an important intermediate compound for the production of pharmaceuticals, and a production method with high efficiency has been demanded.
[12] for example,
[13] (1) U.S. Pat. Nos. 3,629,438 and 3,686,216 disclose benzothiophene-1,1-dioxide derivatives represented by the following formula (X) having fungicidal and bactericidal activity.
[14]
[15] Wherein X ^X represents halogen, nitro, alkyl, alkoxy, haloalkyl, carboxy or sulfonylhalogen,
[16] Y ^X represents hydrogen, lower alkyl, lower alkoxy, halogen or hydroxyl group,
[17] Z ^X represents alkyl, alkoxy, halogen, carboxy, haloalkyl or nitro,
[18] aX represents an integer of 0 or 2,
[19] bX represents an integer of 2,
[20] cX represents 0 or an integer of 1 to 5, or
[21] dX represents 0 or an integer of 1 to 4.
[22] (2) In the specification of FR1,585,930, a compound represented by the following formula (Y) is described as an intermediate compound of a diuretic, but there is no description of biological activity.
[23]
[24] In the above formula, R ^1Y represents a hydrogen atom, a halogen atom or a C _1-3 alkyl group, and R ^2Y and R ^3Y represent a hydrogen atom or a C _1-3 alkyl group.
[25] (3) SU591474 The specification discloses that the compound represented by the following formula (Z) has anticonvulsant activity.
[26]
[27] In the above formula, R ^Z , R ^1Z , R ^2Z and R ^3Z represent a hydrogen atom or a methyl group.
[28] (4) EP50326 discloses that a compound represented by the following formula (U) has a urine-stimulating activity (the description of the group is taken from the necessary part).
[29]
[30] In the above formula R and R ^{1U 2U} are each a hydrogen atom or a C _1~6 alkyl, C _3~6 cycloalkyl group or one or two halogen atom, a hydroxyl group, a represents a phenyl group may be substituted with C _1~6 alkyl or alkoxy, R ^3U represents a hydrogen atom or Z ^U , Z ^U represents a C _1-6 alkyl group or CR ^4U R ^5U R ^6U , R ^4U and R ^5U represent a hydrogen atom or a C _1-6 alkyl group, and R ^6U represents COOH , CH ₂ -OH, a C _1-6 alkoxycarbonyl group or a hydroxyminocarbonyl group, X ^U represents a hydrogen atom, a halogen atom or a C _1-6 alkyl group, nU represents 1 or 2, and mU represents 0 to 2 .
[31] (5) In the specification of WO9527710, it is described that the compound represented by the following formula (V) has antioxidant activity of low specific gravity lipoprotein (LDL).
[32]
[33] R ^'in formula ^V represents a t- butyl, R ^1V denotes a hydrogen atom, a lower alkyl group or an acyl group, and the dashed line represents an optional bond, R ^2V and ^3V R is an alkyl group which may be substituted or may be substituted with a hydrogen atom, R ^4V represents nothing when there is any bond, and has the same meaning as R ^{3V when} no bond is present, and nV represents 0-2.
[34] (6) JP-A No. 10-298180 describes that a compound represented by the following formula (W) has a dopamine receptor antagonistic action.
[35]
[36] In the above formula, A ^Z is a group represented by the formula or (In these formulas, Z ^W represents an oxygen atom or a sulfur atom; R ^1W , R ^2W , R ^3W and R ^4W are the same or different and represent a hydrogen atom and the like); E ^W and F ^W are the same or different ^and are CH, which may be substituted with a nitrogen atom or X ^W or Y ^W ; X ^W is linear or branched C _1-3 alkyloxy substituted by straight-chain or branched C _1-6 alkyloxy, C _3-8 cycloalkyloxy or C _3-8 cycloalkyl; Y is a group of formula (In the formula, G ^W is -CONH-, -C (O) O-, -NHCO- , or -OC (O) -; R ^5W is (a) linear or branched chain C _1~6 alkyl, (b ) C _3~8 cycloalkyl, (c) C _7~12 spiro-alkyl, (d) C _7~12 bicycloalkyl, (e) aryl, (f) aralkyl, (g) heteroaryl-alkyl, (h) A non-aromatic heterocyclic group which may be substituted by a phenyl group, or (i) C _3-8 cycloalkyl C _1-3 alkyl,
[37] i) straight or C _1~6 alkyl, ii) C _1~8 alkyloxy, iii) a straight or branched C _1~3 haloalkyl, iv of branched), halogen, v) C _3~8 cycloalkyl , vi) carboxy, vii) alkyloxycarbonyl, viii) acyl, ix) formyl or x) nitro; nW represents an integer of 1 to 3, pW represents an integer of 1 to 3, and is substituted by (CH ₂ ) _nW and (CH ₂ ) _pW linear or branched C _1-6 alkyl or C _1-3 haloalkyl .
[38] (7) Japanese Patent Application Laid-Open No. 10-513470 The specification discloses that a compound having the following formula (T) or a pharmaceutically acceptable salt or solvate thereof has an effect of inhibiting the effect of IL-6.
[39]
[40] In the above formula, R ^1T and R ^3T are independently hydrogen, -CH ₃ , -C (O) - (C _1-6 alkyl) or -C (O) -Ar ^T (where Ar ^T is optionally substituted Phenyl;
[41] R ^2T is selected from the group consisting of pyrrolidino, hexamethyleneimino and piperidino.
[42] (8) In Japanese Patent Application Laid-Open No. 11-49765, it is described that a compound represented by the following formula (S) or a salt thereof has an excellent neurodegeneration-inhibiting action.
[43]
[44] In the above formula, R ^1S and R ^2S are each a hydrogen atom or a hydrocarbon group which may have a substituent, or R ^1S and R ^2S form a 3- to 8-membered isocyclic or heterocyclic ring which may have a substituent together with the adjacent carbon atom , R ^3S represents a hydrogen atom, a lower alkyl which may have a substituent or an aromatic group which may have a substituent, R ^4S represents (1) an aromatic group which may have a substituent, (2) an aromatic group which may have a substituent, (3) Acyl, X ^S and Y ^S are each an oxygen atom or a sulfur atom which may be oxidized, and the aliphatic hydrocarbon group which may have a substituent It is a single bond or a double bond, ring A ^{S S} -R ^4S formula -X which may have a substituent other than the groups represented by (wherein each symbol is the same also as defined above) represents a good benzene ring. only, And when X ^S and Y ^S are oxygen atoms, R ^4S is not an acyl group.
[45] (9) Further, the following compounds are known.
[46] Compound 1: 3- (thiophen-2-yl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene (Maybrize, catalog number KM 08156)
[47] Compound 2: 6-Nitro-3- (thiophen-2-yl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene (Maybridge, catalog number KM 08165)
[48] Compound 3: 3- (thiophen-2-yl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene (Maybridge Corporation, catalog number KM 08138)
[49] Compound (4): 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene (Maybridge, catalog number KM 08140)
[50] Compound (5): 4,5-dimethyl-1,1-dioxide benzo [b] thiophene (CAS registration number 102036-04-4),
[51] Compound (6): 4,6-dimethyl-1,1-dioxide benzo [b] thiophene (CAS Registry No. 102036-05-5),
[52] Compound (7): 4,7-dimethyl-1,1-dioxide benzo [b] thiophene (CAS Registry No. 102036-06-6),
[53] Compound (8): 5,6-dimethyl-1,1-dioxide benzo [b] thiophene (CAS Registry No. 102036-07-7)
[54] Compound (9): 5,7-dimethyl-1,1-dioxide benzo [b] thiophene (CAS registration number 102036-08-8)
[55] Compound (10): 6,7-dimethyl-1,1-dioxide benzo [b] thiophene (CAS registration number 102036-09-9),
[56] Compound (11): 4-carboxymethyl-1,1-dioxide benzo [b] thiophene (CAS Registry No. 102539-83-3),
[57] Compound (12): 6- (2,2-bis (ethoxycarbonyl) ethenyl) amino-1,1-dioxide benzo [b] thiophene (CAS registration number 118675-43-7)
[58] Compound (13): 4-methylaminocarbonyloxy-1,1-dioxide benzo [b] thiophene (CAS registry number 13687-26-8),
[59] Compound (14): 5- (2- (N- (5-Methoxy-1,2,3,4-tetrahydronaphthalen-1-ylmethyl) Benzo [b] thiophene (CAS Registry No. 188110-86-3),
[60] Compound (15): 5- (2-hydroxyethyl) -1,1-dioxide benzo [b] thiophene (CAS registration number 188111-49-1)
[61] Compound (16): 5-Bromo-7-methyl-1,1-dioxide benzo [b] thiophene (CAS registry number 19076-24-5)
[62] Compound (17): 7-bromo-5-methyl-1,1-dioxide benzo [b] thiophene (CAS registry number 19076-25-6)
[63] Compound (18): 5-Bromo-6-methyl-1,1-dioxide benzo [b] thiophene (CAS registry number 19076-26-7)
[64] Compound (19): 5-Bromo-4-methyl-1,1-dioxide benzo [b] thiophene (CAS registry number 19076-27-8)
[65] Compound (20): 6-bromo-5-methyl-1,1-dioxide benzo [b] thiophene (CAS registry number 19076-28-9)
[66] Compound (21): 4-Bromo-5-methyl-1,1-dioxide benzo [b] thiophene (CAS registry number 19076-29-0)
[67] Compound (22): 6-amino-1,1-dioxide benzo [b] thiophene (CAS registry number 20503-40-6)
[68] Compound (23): 6-acetylamino-1,1-dioxide benzo [b] thiophene (CAS registry number 20503-41-7)
[69] Compound (24): 6- (4-diethylaminophenyl) -1,1-dioxide benzo [b] thiophene (CAS Registry No. 33431-95-7)
[70] Compound (25): 1,1-Dioxidothieno [2,3-b] pyridine (CAS Registry No. 37049-39-1),
[71] Compound (26): 1,1-Dioxidothieno [3,2-b] pyridine (CAS Registry No. 37049-40-4),
[72] Compound (27): 1,1-Dioxanthieno [2,3-c] pyridine (CAS Registry No. 37049-41-5),
[73] Compound (28): 5-amino-1,1-dioxide benzo [b] thiophene (CAS Registry Number 51956-01-5)
[74] Compound (29): 5- (3-Methyl-5-oxo-4,5-dihydropyrazol-1-yl) -1,1-dioxide benzo [b] thiophene (CAS Registry Number 51956-06-0 ),
[75] Compound (30): 4- (2- (1,1-dioxide benzo [b] thiophen-3-yl) ethyl) -1,1-dioxide benzo [b] thiophene (CAS Registry No. 57011-92-4 ),
[76] Compound (31): 7-methyl-1,1-dioxide thieno [2,3-c] pyridine (CAS registration number 76905-90-3)
[77] Compound (32): 1,1-dioxide benzo [b] thiophene (CAS Registry No. 825-44-5),
[78] Compound (33): 4- (4-methoxyphenyl) -1,1-dioxide thieno [3,2-c] pyridine (CAS Registry No. 97104-25-1).
[79] (10) As a method for producing the compound represented by the formula (XI), for example, a method represented by the following reaction formula (2) is known.
[80] These are described in references (Japanese Chemical Society), 1966, 87 (2), 186-189, J. Org. Chem. , 1953, Vol. 18, 1511 and J. Org. Chem. 1973, Vol. 38, 146].
[81]
[82] In the above Reaction Scheme 2, Me represents a methyl group, Ac represents an acetyl group, and NBS represents N-bromosuccinimide.
[83] The process represented by the reaction formula 2 is a process in which the total number of processes is 5 or 6, and in the oxidation reaction from the compound represented by the formula XI-A-6 to the compound represented by the formula XI, expensive silver oxide is used.
[84] Further, as a method for producing the compound represented by the formula (XI), a method represented by the following reaction formula 3 is disclosed in the specification of Japanese Patent Application Laid-Open No. 6-49058.
[85]
[86] In the above Reaction Scheme 3, Et represents an ethyl group.
[87] In the method shown in the reaction formula 3, the total number of steps is 5, and the total yield is about 2 to 3%.
[88] See also Tetrahedron Letters, 1996, Vol. 37, No. 19, 3243 and Tetrahedron Letters 1990, Vol. 31, No. 28, 4011) discloses a reaction in which ketones are converted into nitriles and then dehydrogenated to convert into aromatic rings (Scheme 4).
[89]
[90] In the above Reaction Scheme 4, TMS represents a trimethylsilyl group and DDQ represents 2,3-dichloro-5,6-dicyano-1,4-benzoquinone.
[91] This reaction is carried out by converting the cyclic ketone represented by the formula (XI-C-1) into cyanohydrin and dehydrating it to the nitrile represented by the formula (XI-C-2) To obtain an aromatic nitrile.
[1] The present invention relates to an inhibitor for the production of interleukin-6 (hereinafter abbreviated as IL-6) and / or interleukin-12 (hereinafter abbreviated as IL-12) containing a fused thiophene derivative and a condensed thiophene derivative as an active ingredient .
[2] More particularly, the present invention relates to an inhibitor of IL-6 and / or IL-12 production containing a conjugated thiophene derivative represented by the following general formula (I) and a non-toxic salt thereof as an active ingredient and a novel condensed thiophene derivative represented by the general formula , Non-toxic salts thereof and a process for their preparation.
[3]
[4] In the above formulas, all symbols have the same meanings as defined below.
[5] The present invention also relates to a process for preparing a compound represented by the formula (XI), which is an intermediate of the compound represented by the formula (I).
[92] The inventors of the present invention have conducted intensive studies to find a compound having IL-6 and / or IL-12 production inhibitory activity, and as a result, found that the condensed thiophene derivative represented by formula (I) achieves the object.
[93] The condensed heterocyclic compounds represented by the formula (I) of the present invention are heretofore unknown compounds as IL-6 and / or IL-12 production inhibitors. The condensed thiophene derivative represented by the formula (IA) is a novel compound which has not been known so far.
[94] Further, the inventors of the present invention have conducted intensive studies to discover a novel production method which can be efficiently produced at low cost, and as a result, found a method shown in the following reaction formula (5).
[95]
[96] In the conventional method, 5 to 6 processes are required. In the present invention, however, the number of processes can be shortened by three processes and the process can be efficiently performed. Also, it has been confirmed that the production cost can be reduced in the mass synthesis, and the present invention has been completed.
[97] According to the present invention,
[98] <1> Interleukin-6 and / or an interleukin-12 production inhibitor containing a condensed thiophene derivative represented by the following formula (I), an N-oxide derivative thereof or a non-toxic salt thereof as an active ingredient,
[99] Formula I
[100]
[101] In the above formulas, Represents a single bond or a double bond,
[102] Y is
[103] or
[104] (ii) a hydrogen atom
[105] (only, Represents a double bond, Y represents a hydrogen atom,
[106] Is a single bond, Y is ),
[107] m and n each independently represent 0 or an integer of 1 to 2, p represents 0 or an integer of 1 to 4, q represents 0 or an integer of 1 to 5,
[108] Z represents a single bond, a C _1-8 alkylene group, a C _2-8 alkenylene group or a C _2-8 alkynylene group,
[109] The
[110] (i) a benzene ring or
[111] (ii) a 6-membered monocyclic heterocyclic aryl containing 1 to 2 nitrogen atoms,
[112] The
[113] (i) a C ₃ to C ₁₅ monocyclic, bicyclic, tricyclic carbocyclic ring or
[114] (ii) a monocyclic, bicyclic or tricyclic heterocycle having 4 to 18 members including 1 to 4 nitrogen atoms, 1 to 2 oxygen atoms and / or 1 sulfur atom,
[115] p R &lt; ¹ &gt; are each independently
[116] (i) a C _1-8 alkyl group,
[117] (ii) a C _2-8 alkenyl group,
[118] (iii) a C _2-8 alkynyl group,
[119] (iv) a nitro group,
[120] (v) a cyano group,
[121] (vi) a halogen atom,
[122] (vii) Cyc ¹ group,
[123] (viii) a C _1-8 alkyl group, a C _2-8 alkenyl group or a C _2-8 alkynyl group substituted by a halogen atom or a Cyc ¹ group, or
[124] (ix) -A ¹ -A ² -A ³ ,
[125] A ¹ is
[126] (i) single bond,
[127] (ii) a C _1-8 alkylene group,
[128] (iii) a C _2-8 alkenylene group or
[129] (iv) a C _2-8 alkynylene group,
[130] A ² is
[131] (i) -O- group,
[132] (ii) -NR ³ - group,
[133] (iii) -C (O) - group,
[134] (iv) -CH (OH) - group,
[135] (v) -C (O) NR 4 - group,
[136] (vi) -NR &lt; ⁵ &gt; C (O)
[137] (vii) -C (O) O- group,
[138] (viii) -OC (O) - group,
[139] (ix) -SO ₂ NR ⁶ - group,
[140] (x) -NR ⁷ SO ₂ - group,
[141] (xi) -C (O) NR &lt; ⁹ &gt; O- group,
[142] (xii) -OC (O) NR &lt; ¹⁰ &gt; - group,
[143] (xiii) -NR ¹¹ C (O) NR ¹² - group,
[144] (xiv) -NR &lt; ¹³ &gt; C (O) O- group or
[145] (xv) -OC (O) O- group,
[146] [Wherein R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁹ , R ¹⁰ , R ¹¹ , R ¹² and R ¹³ each independently represent a hydrogen atom, a C _1-8 alkyl group, ¹ group, a -OR ¹⁴ group (in which R ¹⁴ represents a hydrogen atom or a C _1-8 alkyl group) or a C _1-8 alkyl group substituted with a cyano group, and each group represented by A ² represents a The combined hand is coupled to A ³ ],
[147] A ³ is
[148] (i) a hydrogen atom,
[149] (ii) a C _1-8 alkyl group,
[150] (iii) a C _2-8 alkenyl group,
[151] (iv) a C _2-8 alkynyl group,
[152] (v) Cyc group ¹ or
[153] (vi) a C _1-8 alkyl group, a C _2-8 alkenyl group or a C _2-8 alkynyl group substituted with 1 to 3 groups selected from the following (a) to (i)
[154] (a) a halogen atom,
[155] (b) a cyano group,
[156] (c) -P (O) (R ¹⁵ ) ₂ group,
[157] ^{(d) -Si (R 16)} 3 group,
[158] (e) Cyc ¹ group,
[159] (f) -C (O) R &lt; ¹⁷ &gt; groups,
[160] (g) -OR ¹⁸ groups,
[161] (h) -NR ¹⁹ R ²⁰ group,
[162] (i) -SR ²¹ group;
[163] There is a plurality of R ¹⁵ each independently represents a hydroxyl group or C _1~8 alkoxy,
[164] The plural R &lt; ¹⁶ &gt; s each independently represent a C _1-8 alkyl group,
[165] R ¹⁷ is
[166] (i) a hydrogen atom,
[167] (ii) a C _1-8 alkyl group,
[168] (iii) a hydroxyl group,
[169] (iv) a C _1-8 alkoxy group,
[170] (v) Cyc group ¹ or
[171] (vi) -NR ²² R ²³ group: wherein, R ²² denotes a C _1~8 alkyl group substituted by a hydrogen atom, C _1~8 alkyl group, a phenyl group, a phenyl group, R ²³ is a hydrogen atom, C _1~8 alkyl group , Cyc substituted with ¹ group Cyc ¹ or a group or an NR ²⁴ R ²⁵ group (R ²⁴ and R ²⁵ represents a C _1~8 alkyl group substituted by a hydrogen atom, C _1~8 alkyl group, a phenyl group, a phenyl group, each independently) _{Represents a} C _1-8 alkyl group,
[172] R ¹⁸ is
[173] (i) a hydrogen atom,
[174] (ii) a C _1-8 alkyl group,
[175] (iii) a C _2-8 alkenyl group,
[176] (iv) Cyc ¹ or a group
[177] (v) a Cyc ¹ group, a Si (R ²⁶ ) ₃ group (in which R ²⁶ each independently represents a C _1-8 alkyl group) or a -OR ²⁷ group (in which R ²⁷ is a hydrogen atom, C denotes a C _1-8 alkyl group substituted by _{1 to 8} represents an alkyl group or a C _2~5 acyl),
[178] R ¹⁹ is
[179] (i) a hydrogen atom,
[180] (ii) a C _1-8 alkyl group,
[181] (iii) a phenyl group or
[182] (iv) a C _1-8 alkyl group substituted with a phenyl group,
[183] R ²⁰ is
[184] (i) a hydrogen atom,
[185] (ii) a C _1-8 alkyl group,
[186] (iii) -C (O) R ²⁸ group [wherein R ²⁸ represents a C _1-8 alkyl group, a C _1-8 alkoxy group, a Cyc ¹ group or a NR ²⁹ R ³⁰ group (in which R ²⁹ and R ³⁰ are Each independently represents a hydrogen atom or a C _1-8 alkyl group)],
[187] (iv) Cyc ¹ or a group
[188] (v) Cyc represents a C _1~8 alkyl group substituted with ^one group or cyano group,
[189] R ²¹ is
[190] (i) a hydrogen atom,
[191] (ii) a C _1-8 alkyl group or
[192] (iii) represents a group Cyc ^1,
[193] Cyc ¹
[194] (i) a C ₃ to C ₁₅ monocyclic, bicyclic, tricyclic carbocyclic ring or
[195] (ii) a monocyclic, bicyclic or tricyclic heterocycle having 4 to 18 members including 1 to 4 nitrogen atoms, 1 to 2 oxygen atoms and / or 1 sulfur atom,
[196] These carbocyclic or heterocyclic rings may contain one or more
[197] (i) C _1~8 alkyl group, (ii) C _2~8 alkenyl group, (iii) C _2~8 alkynyl group, (iv) oxo, (v) cyano, (vi) nitro groups, (vii) A trihalomethyl group, (iii) a halogen atom, (x) a diphenylmethyl group, (xi) a triphenylmethyl group, (xii) a Cyc ² group, (xiii) -OR ³¹ group, xiv) -SR ³² group, (xv) -NR ³³ R ^{34 _{group, (xvi) -SO 2 NR 35}} R 36 group, (xvii) -C (O) R 37 group, or (xviii) Cyc ² group, a hydroxyl group, A halogen atom or a C _1-8 alkyl group substituted with a -C (O) -Cyc ² group, a C _2-8 alkenyl group or a C _2-8 alkynyl group,
[198] R ³¹ and R ³² each independently represent a hydrogen atom, a C _1-8 alkyl group or a Cyc ² group,
[199] R ³³ represents a hydrogen atom or a C _1-8 alkyl group,
[200] R ³⁴ represents a hydrogen atom, a C _1-8 alkyl group or a -C (O) -Cyc ² group,
[201] R ³⁵ represents a hydrogen atom or a C _1-8 alkyl group,
[202] R ³⁶ represents a hydrogen atom, a C _1-8 alkyl group or a Cyc ² group,
[203] R ³⁷ is a hydrogen atom, C _1~8 alkyl groups, -OR ³⁸ groups, -NR ³⁹ R ⁴⁰ group, Cyc ² group or a group Cyc ² or -C (O) -Cyc ² represents a C _1~8 alkyl group substituted by ,
[204] R ³⁸ , R ³⁹ and R ⁴⁰ each independently represent a hydrogen atom or a C _1-8 alkyl group which may be substituted with Cyc ² ,
[205] Cyc ²
[206] (i) a C ₃ to C ₁₅ monocyclic, bicyclic, tricyclic carbocyclic ring or
[207] (ii) a monocyclic, bicyclic or tricyclic heterocycle having 4 to 18 members including 1 to 4 nitrogen atoms, 1 to 2 oxygen atoms and / or 1 sulfur atom,
[208] These carbocyclic or heterocyclic rings may contain one or more
[209] (i) C _1~8 alkyl group, (ii) C _2~8 alkenyl group, (iii) C _2~8 alkynyl group, (iv) oxo, (v) cyano, (vi) nitro groups, (vii) trihaloalkyl group, (viii) Romero Talk time trihalomethyl, (ix) halogen atoms, (x) -OR ⁴¹ group, (xi) -SR ⁴² group, (xii) -NR ⁴³ R ⁴⁴ group, (xiii) - SO ₂ NR ⁴⁵ R ⁴⁶ group, (xiv) -C (O) R ⁴⁷ group, (xv) a C _1-8 alkyl group, a C _2-8 alkenyl group or a C _2-8 alkynyl group substituted with a hydroxyl group or a halogen atom xvi) phenyl group,
[210] R ⁴¹ , R ⁴² , R ⁴³ , R ⁴⁴ , R ⁴⁵ and R ⁴⁶ each independently represent a hydrogen atom or a C _1-8 alkyl group,
[211] R ⁴⁷ represents a hydrogen atom, a C _1-8 alkyl group or a C _1-8 alkoxy group,
[212] q R &lt; ² &gt; are each independently,
[213] (i) a C _1-8 alkyl group,
[214] (ii) a C _2-8 alkenyl group,
[215] (iii) a C _2-8 alkynyl group,
[216] (iv) -OR ⁴⁸ groups,
[217] (v) -NR ⁴⁹ R ⁵⁰ group,
[218] (vi) -C (O) R &lt; ^{51 &gt;} groups,
[219] (vii) a nitro group,
[220] (viii) a cyano group,
[221] (ix) a halogen atom or
[222] (x) -OR ⁴⁸ group, -NR ⁴⁹ R ⁵⁰ group, -C (O) R ⁵¹ group, C _1-8 alkyl group substituted by halogen atom or Cyc ³ group, C _2-8 alkenyl group or C _2-8 Alkynyl group,
[223] R ⁴⁸ is
[224] (i) a hydrogen atom,
[225] (ii) a C _1-8 alkyl group,
[226] (iii) a C _2-8 alkenyl group,
[227] (iv) a C _2-8 alkynyl group,
[228] (v) Cyc group ³ or
[229] (vi) a C _1-8 alkyl group substituted by a halogen atom, -OR ⁵² group, -NR ⁵³ R ⁵⁴ group, -C (O) R ⁵⁵ group or Cyc ³ group, C _2-8 alkenyl group or C _2-8 An alkynyl group,
[230] R ⁴⁹ and R ⁵⁰ each independently represent a hydrogen atom, a C _1-8 alkyl group or a -COR ⁵⁹ group,
[231] R ⁵¹ represents a hydrogen atom, a C _1-8 alkyl group, a hydroxyl group, a C _1-8 alkoxy group or an -NR ⁶⁰ R ⁶¹ group,
[232] R ⁵² represents a hydrogen atom, a C _1-8 alkyl group, a Cyc ³ group or a C _1-8 alkyl group substituted with a Cyc ³ group,
[233] R ⁵³ and R ⁵⁴ each independently represent a hydrogen atom, C _1~8 alkyl, C _2~8 alkenyl, C _2~8 alkynyl group or -C (O) R ⁵⁶ group (a group, R ⁵⁶ is C _{1~ A} C _1-8 alkoxy group, a Cyc ³ group or a Cyc ³ group substituted with a C _1-8 alkyl group, a C _1-8 alkoxy group, a Cyc ³ group or a Cyc ³ group), R ⁵⁵ represents a hydroxyl group, a C _1-8 alkoxy group or a -NR ⁵⁷ R ⁵⁸ group , R ⁵⁷ and R ⁵⁸ each independently represent a hydrogen atom, a C _1-8 alkyl group or a C _1-8 alkyl group substituted with a Cyc ³ group)
[234] R ⁵⁹ represents a C _1-8 alkyl group or a C _1-8 alkoxy group,
[235] R ⁶⁰ and R ⁶¹ each independently represent a hydrogen atom or a C _1-8 alkyl group,
[236] Cyc ³
[237] (i) a C ₃ to C ₁₅ monocyclic, bicyclic, tricyclic carbocyclic ring or
[238] (ii) a monocyclic, bicyclic or tricyclic heterocycle having 4 to 18 members including 1 to 4 nitrogen atoms, 1 to 2 oxygen atoms and / or 1 sulfur atom,
[239] These carbocyclic or heterocyclic rings may contain one or more
[240] (i) C _1~8 alkyl group, (ii) C _1~8 alkoxy group, (iii) nitro group, (iv) halogen atom, (v) cyano, (vi) hydroxy group, (vii) benzyloxy group, ( (viii) -NR ⁶² R ⁶³ group, (ix) -COOR ⁶⁴ group, (x) trihalomethyl group, (xi) trihalomethoxy group, (xii) phenyl group, (Xv) a C _1-8 alkyl group substituted with a phenyl group, a phenoxy group, a phenylthio group, a hydroxyl group, a -NR ⁶² R ⁶³ group or a -COOR ⁶⁴ group, or a C _1-8 alkoxy group,
[241] R ⁶² and R ⁶³ each independently represent a hydrogen atom or a C _1-8 alkyl group,
[242] R ⁶⁴ represents a hydrogen atom or a C _1-8 alkyl group.
[243] However, A ² is ^{(vi) -NR 5 C (O} ) - _{^{group, (x) -NR 7 SO 2}} - ^{group, (xiv) -NR 13 C (} O) O- group, or (xv) -OC (O ) O-, A ³ does not represent a hydrogen atom.
[244] <2> A novel condensed thiophene derivative represented by the following formula (IA), an N-oxide derivative thereof or a non-toxic salt thereof,
[245]
[246] In the above formula Represents a single bond or a double bond,
[247] Y is
[248] or
[249] (ii) a hydrogen atom
[250] (only, Represents a double bond, Y represents a hydrogen atom,
[251] Is a single bond, Y is ),
[252] m and n each independently represent 0 or an integer of 1 to 2,
[253] p represents 0 or an integer of 1 to 4,
[254] q represents 0 or an integer of 1 to 5,
[255] Z represents a single bond, a C _1-8 alkylene group, a C _2-8 alkenylene group or a C _2-8 alkynylene group,
[256] The
[257] (i) a benzene ring or
[258] (ii) a 6-membered monocyclic heterocyclic aryl containing 1 to 2 nitrogen atoms,
[259] The
[260] (i) a C ₃ to C ₁₅ monocyclic, bicyclic, tricyclic carbocyclic ring or
[261] (ii) a monocyclic, bicyclic or tricyclic heterocycle having 4 to 18 members including 1 to 4 nitrogen atoms, 1 to 2 oxygen atoms and / or 1 sulfur atom,
[262] p &lt; RTI ID = 0.0 &gt; Ri &lt; / RTI &^gt;
[263] (i) a C _1-8 alkyl group,
[264] (ii) a C _2-8 alkenyl group,
[265] (iii) a C _2-8 alkynyl group,
[266] (iv) a nitro group,
[267] (v) a cyano group,
[268] (vi) a halogen atom,
[269] (vii) Cyc ¹ group,
[270] (viii) a C _1-8 alkyl group, a C _2-8 alkenyl group or a C _2-8 alkynyl group substituted by a halogen atom or a Cyc ¹ group, or
[271] (ix) -A ¹ -A ² -A ³ ,
[272] A ¹ is
[273] (i) single bond,
[274] (ii) a C _1-8 alkylene group,
[275] (iii) a C _2-8 alkenylene group or
[276] (iv) a C _2-8 alkynylene group,
[277] A ² is
[278] (i) -O- group,
[279] (ii) -NR ³ - group,
[280] (iii) -C (O) - group,
[281] (iv) -CH (OH) - group,
[282] (v) -C (O) NR 4 - group,
[283] (vi) -NR &lt; ⁵ &gt; C (O)
[284] (vii) -C (O) O- group,
[285] (viii) -OC (O) - group,
[286] (ix) -SO ₂ NR ⁶ - group,
[287] (x) -NR ⁷ SO ₂ - group,
[288] (xi) -C (O) NR &lt; ⁹ &gt; O- group,
[289] (xii) -OC (O) NR &lt; ¹⁰ &gt; - group,
[290] (xiii) -NR ¹¹ C (O) NR ¹² - group,
[291] (xiv) -NR &lt; ¹³ &gt; C (O) O- group or
[292] (xv) -OC (O) O- group,
[293] (Wherein R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁹ , R ¹⁰ , R ¹¹ , R ¹² and R ¹³ each independently represent a hydrogen atom, a C _1-8 alkyl group, ¹ group, a -OR ¹⁴ group (in which R ¹⁴ represents a hydrogen atom or a C _1-8 alkyl group) or a C _1-8 alkyl group substituted with a cyano group, and each group represented by A ² represents a The combined hand is coupled to A ³ ),
[294] A ³ is
[295] (i) a hydrogen atom,
[296] (ii) a C _1-8 alkyl group,
[297] (iii) a C _2-8 alkenyl group,
[298] (iv) a C _2-8 alkynyl group,
[299] (v) Cyc group ¹ or
[300] (vi) a C _1-8 alkyl group, a C _2-8 alkenyl group or a C _2-8 alkynyl group substituted with 1 to 3 groups selected from the following (a) to (i)
[301] (a) a halogen atom,
[302] (b) a cyano group,
[303] (c) -P (O) (R ¹⁵ ) ₂ group,
[304] ^{(d) -Si (R 16)} 3 group,
[305] (e) Cyc ¹ group,
[306] (f) -C (O) R &lt; ¹⁷ &gt; groups,
[307] (g) -OR ¹⁸ groups,
[308] (h) -NR ¹⁹ R ²⁰ group,
[309] (i) -SR ²¹ group;
[310] There is a plurality of R ¹⁵ each independently represents a hydroxyl group or C _1~8 alkoxy,
[311] The plural R &lt; ¹⁶ &gt; s each independently represent a C _1-8 alkyl group,
[312] R ¹⁷ is
[313] (1) a hydrogen atom,
[314] (ii) a C _1-8 alkyl group,
[315] (iii) a hydroxyl group,
[316] (iv) a C _1-8 alkoxy group,
[317] (v) Cyc group ¹ or
[318] (vi) -NR ²² R ²³ group: wherein, R ²² denotes a C _1~8 alkyl group substituted by a hydrogen atom, C _1~8 alkyl group, a phenyl group, a phenyl group, R ²³ is a hydrogen atom, C _1~8 alkyl group , Cyc substituted with ¹ group Cyc ¹ or a group or an NR ²⁴ R ²⁵ group (R ²⁴ and R ²⁵ represents a C _1~8 alkyl group substituted by a hydrogen atom, C _1~8 alkyl group, a phenyl group, a phenyl group, each independently) _{Represents a} C _1-8 alkyl group,
[319] R ¹⁸ is
[320] (i) a hydrogen atom,
[321] (ii) a C _1-8 alkyl group,
[322] (in) C _2-8 alkenyl group,
[323] (iv) Cyc ¹ or a group
[324] (v) a Cyc ¹ group, a Si (R ²⁶ ) ₃ group (in which R ²⁶ each independently represents a C _1-8 alkyl group) or a -OR ²⁷ group (in which R ²⁷ is a hydrogen atom, C denotes a C _1-8 alkyl group substituted by _{1 to 8} represents an alkyl group or a C _2~5 acyl),
[325] R ¹⁹ is
[326] (i) a hydrogen atom,
[327] (ii) a C _1-8 alkyl group,
[328] (iii) a phenyl group or
[329] (iv) a C _1-8 alkyl group substituted with a phenyl group,
[330] R ²⁰ is
[331] (i) a hydrogen atom,
[332] (ii) a C _1-8 alkyl group,
[333] (iii) -C (O) R ²⁸ group [wherein R ²⁸ represents a C _1-8 alkyl group, a C _1-8 alkoxy group, a Cyc ¹ group or a NR ²⁹ R ³⁰ group (in which R ²⁹ and R ³⁰ are Each independently represents a hydrogen atom or a C _1-8 alkyl group)],
[334] (iv) Cyc ¹ or a group
[335] (v) Cyc represents a C _1~8 alkyl group substituted with ^one group or cyano group,
[336] R ²¹ is
[337] (i) a hydrogen atom,
[338] (ii) a C _1-8 alkyl group or
[339] (iii) represents a group Cyc ^1,
[340] Cyc ¹
[341] (i) a monocyclic C of _{3 to 15,} bicyclic, tricyclic carbon ring or triple
[342] (ii) a single, double or triple cyclic heterocycle of 4 to 18 members including 1 to 4 nitrogen atoms, 1 to 2 oxygen atoms and / or 1 sulfur atom,
[343] These carbocyclic or heterocyclic rings may contain one or more
[344] (i) C _1~8 alkyl group, (ii) C _2~8 alkenyl group, (iii) C _2~8 alkynyl group, (iv) oxo, (v) cyano, (vi) nitro groups, (vii) A trihalomethyl group, (iii) a halogen atom, (x) a diphenylmethyl group, (xi) a triphenylmethyl group, (xii) a Cyc ² group, (xiii) -OR ³¹ group, xiv) -SR ³² group, (xv) -NR ³³ R ^{34 _{group, (xvi) -SO 2 NR 35}} R 36 group, (xvii) -C (O) R 37 group, or (xviii) Cyc ² group, a hydroxyl group, A halogen atom or a C _1-8 alkyl group substituted with a -C (O) -Cyc ² group, a C _2-8 alkenyl group or a C _2-8 alkynyl group,
[345] R ³¹ and R ³² each independently represent a hydrogen atom, a C _1-8 alkyl group or a Cyc ² group,
[346] R ³³ represents a hydrogen atom or a C _1-8 alkyl group,
[347] R ³⁴ represents a hydrogen atom, a C _1-8 alkyl group or a -C (O) -Cyc ² group,
[348] R ³⁵ represents a hydrogen atom or a C _1-8 alkyl group,
[349] R ³⁶ represents a hydrogen atom, a C _1-8 alkyl group or a Cyc ² group,
[350] R ³⁷ is a hydrogen atom, C _1~8 alkyl groups, -OR ³⁸ groups, -NR ³⁹ R ⁴⁰ group, Cyc ² group or a group Cyc ² or -C (O) -Cyc ² represents a C _1~8 alkyl group substituted by ,
[351] R ³⁸ , R ³⁹ and R ⁴⁰ each independently represent a hydrogen atom or a C _1-8 alkyl group which may be substituted with Cyc ² ,
[352] Cyc ²
[353] (i) a monocyclic C of _{3 to 15,} bicyclic, tricyclic carbon ring or triple
[354] (ii) a single, double or triple cyclic heterocycle of 4 to 18 members including 1 to 4 nitrogen atoms, 1 to 2 oxygen atoms and / or 1 sulfur atom,
[355] These carbocyclic or heterocyclic rings may contain one or more
[356] (i) C _1~8 alkyl group, (ii) C _2~8 alkenyl group, (iii) C _2~8 alkynyl group, (iv) oxo, (v) cyano, (vi) nitro groups, (vii) A halogen atom, (x) -OR ⁴¹ group, (xi) -SR ⁴² group, (xii) -NR ⁴³ R ⁴⁴ group, (xiii) -SO ₂ NR ⁴⁵ R ⁴⁶ group, (xiv) -C (O) R 47 group, (xv) a hydroxyl group or a halogen atom substituted with C _1~8 alkyl, C _2~8 alkenyl or alkynyl group or C _2~8 (xvi ) Phenyl group,
[357] R ⁴¹ , R ⁴² , R ⁴³ , R ⁴⁴ , R ⁴⁵ and R ⁴⁶ each independently represent a hydrogen atom or a C _1-8 alkyl group,
[358] R ⁴⁷ represents a hydrogen atom, a C _1-8 alkyl group or a C _1-8 alkoxy group,
[359] q R &lt; ² &gt; are each independently,
[360] (i) a C _1-8 alkyl group,
[361] (ii) a C _2-8 alkenyl group,
[362] (iii) a C _2-8 alkynyl group,
[363] (iv) -OR ⁴⁸ groups,
[364] (v) -NR ⁴⁹ R ⁵⁰ group,
[365] (vi) -C (O) R &lt; ^{51 &gt;} groups,
[366] (vii) a nitro group,
[367] (viii) a cyano group,
[368] (ix) a halogen atom or
[369] (x) -OR ⁴⁸ group, -NR ⁴⁹ R ⁵⁰ group, -C (O) R ⁵¹ group, C _1-8 alkyl group substituted by halogen atom or Cyc ³ group, C _2-8 alkenyl group or C _2-8 An alkynyl group,
[370] R ⁴⁸ is
[371] (i) a hydrogen atom,
[372] (ii) a C _1-8 alkyl group,
[373] (iii) a C _2-8 alkenyl group,
[374] (iv) a C _2-8 alkynyl group,
[375] (v) Cyc group ³ or
[376] (vi) a C _1-8 alkyl group substituted by a halogen atom, -OR ⁵² group, -NR ⁵³ R ⁵⁴ group, -C (O) R ⁵⁵ group or Cyc ³ group, C _2-8 alkenyl group or C _2-8 Alkynyl group,
[377] R ⁴⁹ and R ⁵⁰ each independently represent a hydrogen atom, a C _1-8 alkyl group or a -COR ⁵⁹ group,
[378] R ⁵¹ represents a hydrogen atom, a C _1-8 alkyl group, a hydroxyl group, a C _1-8 alkoxy group or an -NR ⁶⁰ R ⁶¹ group,
[379] R ⁵² represents a hydrogen atom, a C _1-8 alkyl group, a Cyc ³ group or a C _1-8 alkyl group substituted with a Cyc ³ group,
[380] R ⁵³ and R ⁵⁴ each independently represent a hydrogen atom, C _1~8 alkyl, C _2~8 alkenyl, C _2~8 alkynyl group or -C (O) R ⁵⁶ group (a group, R ⁵⁶ is C _{1~ A} C _1-8 alkyl group, a C _1-8 alkoxy group, a Cyc ³ group, or a C _1-8 alkyl group substituted with a Cyc ³ group)
[381] R ⁵⁵ is a hydroxyl group, a C _1-8 alkoxy group or -NR ⁵⁷ R ⁵⁸ group (wherein R ⁵⁷ and R ⁵⁸ are each independently a hydrogen atom, a C _1-8 alkyl group or a C _1-8 alkyl group substituted with a Cyc ³ group , &Lt; / RTI &gt;
[382] R ⁵⁹ represents a C _1-8 alkyl group or a C _1-8 alkoxy group,
[383] R ⁶⁰ and R ⁶¹ each independently represent a hydrogen atom or a C _1-8 alkyl group,
[384] Cyc ³
[385] (i) a monocyclic C of _{3 to 15,} bicyclic, tricyclic carbon ring or triple
[386] (ii) a single, double or triple cyclic heterocycle of 4 to 18 members including 1 to 4 nitrogen atoms, 1 to 2 oxygen atoms and / or 1 sulfur atom,
[387] These carbocyclic or heterocyclic rings may contain one or more
[388] (i) C _1~8 alkyl group, (ii) C _1~8 alkoxy group, (iii) nitro group, (iv) halogen atom, (v) cyano, (vi) hydroxy group, (vii) benzyloxy group, ( (viii) -NR ⁶² R ⁶³ group, (ix) -COOR ⁶⁴ group, (x) trihalomethyl group, (xi) trihalomethoxy group, (xii) phenyl group, (Xv) a C _1-8 alkyl group substituted with a phenyl group, a phenoxy group, a phenylthio group, a hydroxyl group, a -NR ⁶² R ⁶³ group or a -COOR ⁶⁴ group, or a C _1-8 alkoxy group,
[389] R ⁶² and R ⁶³ each independently represent a hydrogen atom or a C _1-8 alkyl group,
[390] R ⁶⁴ represents a hydrogen atom or a C _1-8 alkyl group.
[391] only,
[392] (1) A ² is (vi) -NR ⁵ C (O) - group, (x) -NR ⁷ SO ₂ - group, (xiv) -NR ¹³ C (O) O- group or O) O- group, A ³ does not denote a hydrogen atom,
[393] (2) Represents a double bond, and when Y represents a hydrogen atom, n represents 1 or 2,
[394] (3) Represents a single bond, and Y represents N represents 2, m represents 0 or 2, p represents 0 or an integer of 1 to 4, A ring and B ring represent a benzene ring, R ¹ represents a C _1-8 alkyl group, C _{1 to 8} alkoxy group, to represent a halogen atom, a carboxyl group, a nitro group or a halogen atom substituted with C _1~8 alkyl group, and that q does not represent 0,
[395] (4) Represents a single bond, and Y represents , N represents 2, m represents 0 or 2, p represents 0 or an integer of 1 to 4, A ring and B ring represent a benzene ring, R ¹ represents a C _1-8 alkyl group, C _{1 to 8} alkoxy group, a halogen atom, a carboxyl group, a nitro group or a halogen atom substituted with C _1~8 alkyl group, when the q represent an integer of 1~5, R ² is C _1~8 alkyl, C _1~8 alkoxy A halogen atom, a carboxy group, a nitro group, or a C _1-8 alkyl group substituted with a halogen atom,
[396] (5) When Y represents a hydrogen atom, n represents 2, p represents 1, and the ring A represents a benzene ring, R ¹ represents a halogen atom, a C _1-8 alkyl group, a phenylsulfonylamino group, Substituted with a C _1-8 alkoxycarbonyl group or a hydroxymonocarbonyl group, such as a methylsulfonylamino group, a 2-methylphenylsulfonylamino group, a 3-methylphenylsulfonylamino group, a 4-methylphenylsulfonylamino group, a hydroxyl group, a C _1-8 alkoxy group, a nitro group or a carboxyl group, _{Lt; RTI} ID = 0.0 &gt; _C8 &lt; / RTI &gt; alkoxy group,
[397] (6) Y represents a hydrogen atom, n represents 2, p represents 2, A ring represents a benzene ring, one R ¹ represents a phenylsulfonylamino group, a 2-methylphenylsulfonylamino group, a 3-methylphenylsulfonylamino group, A methylphenylsulfonylamino group or a 4-methylphenylsulfonylamino group, another R ¹ is not a C _1-8 alkyl group,
[398] (7) Y represents a hydrogen atom, n represents 2, p represents 2 to 3, A ring represents a benzene ring, one R ¹ represents a hydroxyl group, a C _1-8 alkoxy group or a carboxyl group, to indicate a hydroxyl group, C _1~8 alkoxycarbonyl group or a hydroxy C _1~8 alkoxy substituted with amino group, and the other R ¹ is and that it does not represent a halogen atom or a C _1~8 alkyl group,
[399] (8) Y represents a hydrogen atom, n represents 2, p represents 3 to 4, and when A ring represents a benzene ring, 2 to 3 R ¹ do not simultaneously represent a t-butyl group and,
[400] (9) The following compounds (1) to (32) are excluded:
[401] (1) 3- (thiophen-2-yl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
[402] (2) 6-Nitro-3- (thiophen-2-yl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
[403] (3) 3- (thiophen-2-yl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
[404] (4) 4,5-dimethyl-1,1-dioxide benzo [b] thiophene,
[405] (5) 4,6-dimethyl-1,1-dioxide benzo [b] thiophene,
[406] (6) 4,7-dimethyl-1,1-dioxide benzo [b] thiophene,
[407] (7) 5,6-dimethyl-1,1-dioxide benzo [b] thiophene,
[408] (8) 5,7-dimethyl-1,1-dioxide benzo [b] thiophene,
[409] (9) 6,7-dimethyl-1,1-dioxide benzo [b] thiophene,
[410] (10) 4-carboxymethyl-1,1-dioxide benzo [b] thiophene,
[411] (11) 6- (2,2-bis (ethoxycarbonyl) ethenyl) amino-1,1-dioxide benzo [b] thiophene,
[412] (12) 4-Methylaminocarbonyloxy-1, 1-dioxo [b] thiophene,
[413] (13) 5- (2- (N- (5-Methoxy-1,2,3,4-tetrahydronaphthalen-1-ylmethyl) b] thiophene,
[414] (14) 5- (2-hydroxyethyl) -1,1-dioxo [b] thiophene,
[415] (15) 5-Bromo-7-methyl-l, l-dioxide benzo [b] thiophene,
[416] (16) 7-Bromo-5-methyl-l, l-dioxide benzo [b] thiophene,
[417] (17) 5-Bromo-6-methyl-l, l-dioxide benzo [b] thiophene,
[418] (18) 5-bromo-4-methyl-l, l-dioxide benzo [b] thiophene,
[419] (19) 6-bromo-5-methyl-l, l-dioxide benzo [b] thiophene,
[420] (20) 4-Bromo-5-methyl-l, l-dioxide benzo [b] thiophene,
[421] (21) 6-amino-1,1-dioxide benzo [b] thiophene,
[422] (22) 6-acetylamino-l, l-dioxide benzo [b] thiophene,
[423] (23) 6- (4-Diethylaminophenyl) -1,1-dioxo [b] thiophene,
[424] (24) 1,1-dioxo-thieno [2,3-b] pyridine,
[425] (25) 1,1-dioxo-thieno [3,2-b] pyridine,
[426] (26) 1,1-dioxo-thieno [2,3-c] pyridine,
[427] (27) 5-amino-1,1-dioxide benzo [b] thiophene,
[428] (28) 5- (3-methyl-5-oxo-4,5-dihydropyrazol-1-yl) -1,1-dioxide benzo [b] thiophene,
[429] (29) 4- (2- (1,1-dioxide benzo [b] thiophen-3-yl) ethyl) -1,1-dioxide benzo [b] thiophene,
[430] (30) 7-methyl-1,1-dioxo [b] thieno [2,3-c] pyridine,
[431] (31) 1,1-dioxide benzo [b] thiophene or
[432] (32) 4- (4-methoxyphenyl) -1,1-dioxo-thieno [3,2-c] pyridine].
[433] &Lt; 3 > A condensed thiophene derivative represented by the formula (IA), an N-oxide derivative thereof or a non-toxic salt thereof, and
[434] &Lt; 4 > A process for producing a compound represented by the formula (XII), wherein the compound represented by the formula (XII) is subjected to a cyanating reaction to obtain a compound represented by the formula (XIII), followed by dehydrogenation to obtain a compound represented by the formula To a process for producing a compound represented by the formula (XI).
[435]
[436]
[437]
[438]
[439] In the present invention, unless otherwise indicated, the isomers include all of them. Examples of the alkyl group, alkenyl group, alkynyl group, alkoxy group, alkylthio group, alkylene group, alkenylene group and alkynylene group include straight chain and branched chain. (R, S, α, β-isomers, enantiomers, diastereomers) due to the presence of isomers (E, Z, cis, trans) (Optically active substance having a light-emitting property (D, L, d, 1 form), a polar compound (high polarity substance, low polarity substance) by chromatographic separation, an equilibrium compound, .
[440] In the present invention, the N-oxide derivative of the compound represented by the general formula (I) and the general formula (IA) means a compound in which the nitrogen atom of the compound containing nitrogen atom is oxidized among the compounds represented by the general formulas (I) and (IA).
[441] In the present invention, the C _1-8 alkyl group is methyl, ethyl, propyl, butyl, pentyl, hexyl, heptyl, octyl and isomers thereof.
[442] C _2-8 alkenyl groups may be substituted with one or more groups selected from the group consisting of vinyl, propenyl, butenyl, pentenyl, hexenyl, heptenyl, octenyl, butadienyl, pentadienyl, hexadienyl, heptadienyl, octadienyl, Heptatrienyl, octatrienyl, and isomers thereof.
[443] C _2-8 alkynyl group is ethynyl, propynyl, butynyl, pentynyl, hexynyl, heptynyl, octynyl and isomers thereof.
[444] C _1-8 alkylene groups include methylene, ethylene, trimethylene, tetramethylene, pentamethylene, hexamethylene, heptamethylene, octamethylene groups and isomers thereof.
[445] C _2-8 alkenylene groups include ethenylene, propenylene, butenylene, pentenylene, hexenylene, heptenylene, octenylene, and isomers thereof.
[446] C _2-8 alkynylene groups include ethynylene, propynylene, butynylene, pentynylene, hexynylene, heptynylene, octynylene, and isomers thereof.
[447] The halogen atom means chlorine, bromine, fluorine, iodine atom.
[448] C _1-8 alkoxy groups include methoxy, ethoxy, propoxy, butoxy, pentyloxy, hexyloxy, heptyloxy, octyloxy groups and isomers thereof.
[449] The trihalomethyl group is a triple substituted methyl group by chlorine, bromine, fluorine, or iodine atoms.
[450] The trihalomethoxy group is a methoxy group which is triple-substituted by chlorine, bromine, fluorine and iodine atoms.
[451] C _2-5 acyl groups include acetyl, propionyl, butyryl, valeryl, and isomers thereof.
[452] The 6-membered monocyclic hetero ring aryl group containing 1 to 2 nitrogen atoms includes pyridine, pyridine-N-oxide, pyrazine, pyrazine-N-monoxide, pyrazine-N-dioxide, pyrimidine, Monoxide, pyrimidine-N-dioxide, pyridazine, pyridazine-N-monoxide, pyridazine-N-dioxide ring and the like.
[453] Examples of the C _3-15 single ring, double ring and tricyclic carbon ring include cyclopropane, cyclobutane, cyclopentane, cyclohexane, cycloheptane, cyclopentene, cyclohexane, cyclopentadiene, cyclohexadiene, benzene, Examples of the organic peroxides include organic peroxides such as thiophene, thiophene, thiophene, thienylene, indene, indene, naphthalene, azulene, fluorene, phenanthrene, anthracene, acenaphthylene, biphenylene, perhydropentaleene, perhydroindene, dihydronaphthalene, Benzene, toluene, toluene, toluene, toluene, xylene, toluene, toluene, xylene,
[454] A single ring, double ring or tricyclic heterocycle of 4 to 18 members including 1 to 4 nitrogen atoms, 1 to 2 oxygen atoms and / or 1 sulfur atom means 1 to 4 nitrogen atoms, 1 to 2 oxygen Monocyclic, bicyclic or tricyclic heterocyclic aryl or a part or all of the 4 to 18 membered ring containing one atom and / or one sulfur atom.
[455] The single, double or triple cyclic heterocyclic aryl of 4 to 18 members comprising 1 to 4 nitrogen atoms, 1 to 2 oxygen atoms and / or 1 sulfur atom includes pyrrole, pyrrole-N-oxide, Pyrazine, N-oxide, pyrazine-N-monoxide, pyrazine-N-dioxide, pyrimidine, pyrimidine-N-monoxide, pyrimidine-N-oxide, Pyridazine-N-monoxide, pyridazine-N-dioxide, azepine, diazepine, furan, pyran, oxepine, oxazepine, thiophene, thiamine (thiopyran), thiepine, Oxadiazines, oxadiazines, oxadiazines, oxadiazines, thiadiazoles, tiaazines, tadadiazines, thiazepines, thiadiazines, thiadiazoles, oxadiazines, oxadiazines, Isoindole, benzofuran, isobenzofuran, benzothiophene, isobenzothiophene, indazole, quinoline, N-oxide, isoquinoline, isoquinoline-N-oxide, phthalazine, naphthyridine, naphthyridine-N-monoxide, naphthyridine-N-dioxide, quinoxaline, quinoxaline- Oxides, quinoxaline-N-dioxides, quinazoline-N-monooxides, quinazoline-N-dioxides, cinnoline, benzoxazole, benzothiazole, benzoimidazole, carbazole, .
[456] Examples of partially or fully saturated 4 to 18 membered monocyclic, bicyclic or tricyclic heterocyclic rings containing 1 or 2 nitrogen atoms, 1 to 2 oxygen atoms and / or 1 sulfur atom include pyrroline , Pyrrolidine, pyrrolidine-N-oxide, imidazoline, imidazolidine, triazoline, triazolidine, tetrazolene, tetrazolidine, dihydropyridine, dihydropyridine- Pyrazine, dihydropyrazine-N-monoxide, dihydropyrazine-N-dioxide, dihydropyrimidine, dihydropyrimidine-N-monoxide, dihydropyrimidine-N-dioxide, dihydropyridazine, dihydro Pyridazine-N-monoxide, dihydropyridazine-N-dioxide, piperidine, piperidine-N-oxide, piperazine, piperazine-N-monoxide, piperazine- Pyridine, tetrahydropyrimidine-N-monooxa Tetrahydropyrimidine-N-dioxide, tetrahydropyrimidine-N-dioxide, tetrahydropyridazine, tetrahydropyridazine-N-monoxide, tetrahydropyridazine-N-dioxide, dihydrofuran, tetrahydrofuran, dihydropyran, , Dihydrothiophene, tetrahydrothiophene, dihydrothiene (dihydrothiopyran), tetrahydrothiene (tetrahydrothiopyran), dihydrooxazole, tetrahydrooxazole, dihydroisooxazole, tetrahydrothiophene Dihydrothiazole, dihydroisothiazole, tetrahydroisothiazole, morpholine, morpholine-N-oxide, thiomorpholine, thiomorpholine-N-oxide, indoline, Isoindoline, dihydrobenzofuran, perhydrobenzofuran, dihydroisobenzofuran, perhydroisobenzofuran, dihydrobenzothiophene, perhydrobenzothiophene, dihydroisobenzene Thiophene, perhydroisobenzothiophene, dihydroindazole, perhydroindazole, dihydroquinoline, dihydroquinoline-N-oxide, tetrahydroquinoline, tetrahydroquinoline-N-oxide, perhydroquinoline, perhydro Dihydroisoquinoline-N-oxide, tetrahydroisoquinoline, tetrahydroisoquinoline-N-oxide, perhydroisoquinoline-N-oxide, dihydroisoquinoline-N-oxide, dihydroisoquinoline- But are not limited to, phthalazine, tetrahydrophthalazine, perhydropthalazine, dihydronaphthylidine, dihydronaphthyridine-N-monoxide, dihydronaphthyridine-N-dioxide, tetrahydronaphthylidine, tetra Hydroxynaphthylidene-N-oxide, hydronaphthyridine-N-monoxide, tetrahydronaphthylidine-N-dioxide, perhydronaphthylidine, perhydronaphthyridine- Dihydroquinoxaline-N-monoxide, dihydroquinoxaline-N-dioxide, tetrahydroquinoxaline, tetrahydroquinoxaline-N-monoxide, tetrahydroquinoxaline-N-dioxide, perhydro But are not limited to, quinoxaline, quinoxaline, perhydroquinoxaline-N-monoxide, perhydroquinoxaline-N-dioxide, dihydroquinazoline, dihydroquinazoline-N-monoxide, dihydroquinazoline-N-dioxide, tetrahydroquinazoline , Tetrahydroquinazoline-N-monoxide, tetrahydroquinazoline-N-dioxide, perhydroquinazoline, perhydroquinazoline-N-monoxide, perhydroquinazoline-N-dioxide, dihydrocinolinone, tetra There may be mentioned, for example, benzotriazole, benzothiazole, benzothiazole, benzothiazole, benzothiazole, benzothiazole, benzothiazole, benzothiazole, benzothiazole, perhydrobenzoimidazole, Such as benzotriazepine, benzodiazepine, benzothiazepine, benzoazepine, benzodiazepine, indolooxoazepine, indolo tetrahydrooxazepine, indolooxadiazepine, indolo tetrahydrooxadiazepine, , Indolothiazepine, indolo tetrahydrothiazepine, indolothiadiazepine, indolo tetrahydrothiadiazepine, indole azepine, indolo tetrahydroazepine, indolodiazepine, indolo tetrahydrodiamine Benzothiadiazole, benzotriazole, campa, imidazole thiazole, dihydrocarbazole, tetrahydrocarbazole, perhydrocarbazole, dihydroacridine, tetrahydroacridine, perhydro Acridine, 1,3-dioxaneindane, 1,4-dioxane monocyclic ring, and the like.
[457] In the present invention, m is preferably 0 or 2, and particularly preferably 2.
[458] n is preferably 0 or 2, and particularly preferably 2.
[459] p is preferably 1 or 2, and particularly preferably 1.
[460] q is preferably 0 or 1.
[461] Z is preferably a single bond or C _1-8 alkylene, particularly preferably a single bond.
[462] Is preferably a pyridine ring or a benzene ring, particularly preferably a benzene ring.
[463] Is preferably a single or double ring cyclic carbon ring of C _{5 to 10} or a single or double ring of 5 to 10 members including 1 to 3 nitrogen atoms, 1 oxygen atom and / or 1 sulfur atom More preferably a benzene ring, a cyclohexane ring, a thiophene ring, a furan ring, a pyridine ring, a pyrimidine ring and an imidazole ring, particularly preferably a benzene ring or a thiophene ring.
[464] R ¹ is preferably a C _1-8 alkyl group, a nitro group, a cyano group, a C _1-8 alkyl group substituted by a halogen atom, a Cyc ¹ group, a halogen atom or a Cyc ¹ group, or -A ¹ -A ² -A ³ And particularly preferably a C _1-8 alkyl group substituted by a Cyc ¹ group or -A ¹ -A ² -A ³ .
[465] A ¹ is preferably a single bond, a C _1-8 alkylene group or a C 2-8 alkenylene group, particularly preferably a single bond or a C _1-8 alkylene group.
[466] A ² is preferably a group -O-, -NR ³ -, -C (O) -, -C (O) NR ⁴ -, -NR ⁵ C (O) ) O- group, -NR ¹³ C (O) O- group, and particularly preferably -O- group, a -NR ³ - group, -C (O) - group, -C (O) NR ⁴ - group, Lt; ⁵ &gt; C (O) - group.
[467] A ³ is preferably a C _1-8 alkyl group, a Cyc ¹ group or a Cyc ¹ group, a -C (O) R ¹⁷ group, a -NR ¹⁹ R ²⁰ group, a C _1-8 alkyl group substituted with a -OR ¹⁸ group, _{2 to 8} is an alkenyl group and, particularly preferably, Cyc ¹ or a C _1~8 alkyl group substituted with -NR ¹⁹ R ^20.
[468] Cyc ¹ is preferably a C _5-10 single or double ring carbon ring, or a 5- to 10-membered monocyclic or double-ring cyclic carbocyclic ring containing 1 to 3 nitrogen atoms, 1 oxygen atom and / or 1 sulfur atom More preferably a C _5-10 monocyclic carbon ring, or a 5- to 10-membered monocyclic hetero ring containing 1 to 2 nitrogen atoms and / or 1 oxygen atom, more preferably a Benzene ring, piperidine ring, piperazine ring, pyrrolidine ring, pyridine ring and morpholine ring.
[469] R ¹⁹ and R ²⁰ are preferably a hydrogen atom or a C _1-8 alkyl group, and particularly preferably a methyl group, an ethyl group, a propyl group or an isopropyl group.
[470] salt
[471] In the present invention, all non-toxic salts are included. For example, general salts, acid addition salts, hydrate salts and the like.
[472] The compound of the present invention represented by the formula (I) is converted into the corresponding salt by a known method. The salt is preferably water-free without toxicity. Suitable salts include alkali metal (potassium, sodium, etc.) salts, alkaline earth metal (calcium, magnesium etc.) salts, ammonium salts, pharmaceutically acceptable organic amine salts (tetramethylammonium, triethylamine, methylamine, dimethylamine, Monoethanolamine, diethanolamine, tris (hydroxymethyl) amine, lysine, arginine, N-methyl-D-glucamine, etc.) can be mentioned.
[473] The compound of the present invention represented by the formula (I) is converted into the corresponding acid addition salt by a known method. It is preferable that the acid addition salt is water-insoluble without toxicity. Suitable acid addition salts include inorganic acid salts such as hydrochloride, hydrobromide, sulfate, phosphate, nitrate, or acetate, trifluoroacetate, lactate, tartrate, oxalate, fumarate, maleate, citrate, benzoate, Sulfonic acid salts, ethane sulfonic acid salts, benzenesulfonic acid salts, toluene sulfonic acid salts, isethionic acid salts, organic acid salts such as glucuronic acid salts and gluconic acid salts.
[474] The compound of the present invention represented by the formula (I) or a salt thereof may also be converted into a hydrate by a known method.
[475] Preferred compounds in the compound of the present invention represented by the formula (I) include compounds represented by the following formulas IA, IB, IC, ID, IE, IF, IG, IH, IK, , A compound represented by the formula IN, the formula IO, and the formula IP.
[476]
[477] In the above formulas, all symbols have the same meanings as defined above.
[478]
[479] In the above formulas, all symbols have the same meanings as defined above.
[480]
[481] In the above formulas, all symbols have the same meanings as defined above.
[482]
[483] In the above formulas, all symbols have the same meanings as defined above.
[484]
[485] In the above formulas, all symbols have the same meanings as defined above.
[486]
[487] In the above formulas, all symbols have the same meanings as defined above.
[488]
[489] In the above formulas, all symbols have the same meanings as defined above.
[490]
[491] In the above formulas, all symbols have the same meanings as defined above.
[492]
[493] In the above formulas, all symbols have the same meanings as defined above.
[494]
[495] In the above formulas, all symbols have the same meanings as defined above.
[496]
[497] In the above formulas, all symbols have the same meanings as defined above.
[498]
[499] In the above formulas, all symbols have the same meanings as defined above.
[500]
[501] In the above formulas, all symbols have the same meanings as defined above.
[502]
[503] In the above formulas, all symbols have the same meanings as defined above.
[504]
[505] In the above formulas, all symbols have the same meanings as defined above.
[506] Among the compounds represented by the formula (I-A), particularly preferred compounds are those represented by the following formula (I-A ').
[507]
[508] Wherein R ^{1 '} is a C _1-8 alkyl group substituted by a Cyc ¹ group or
[509] (Wherein, A ^{1 'is} a single bond or a C _1~8 alkylene group, A ^2' is a group -O-, -NR ³ - group, -C (O) - group, -C (O) NR ⁴ - or -NR ⁵ C (O) -, and other symbols have the same meanings as defined above, and the other symbols have the same meanings as defined above.
[510] Of the compounds represented by the formula (I-N), particularly preferred compounds are those represented by the following formula (I-N ').
[511]
[512] In the above formulas, all symbols have the same meanings as defined above.
[513] Although the following (1) to (4) are known publicly known compounds, they have not been known as IL-6 production inhibitors and / or IL-12 production inhibitors. The compounds (1) to (4) and their non-toxic salts are also preferable as the compound used in the present invention.
[514] for example,
[515] Compound 1: 3- (thiophen-2-yl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene (Maybridge, catalog number KM 08156)
[516]
[517] Compound (2): 6-Nitro-3- (thiophen-2-yl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene (Maybridge, catalog number KM 08165)
[518]
[519] Compound 3: 3- (thiophen-2-yl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene (Maybridge, catalog number KM 08138)
[520]
[521] Compound (4): 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene (Maybridge, catalog number KM 08140)
[522]
[523] More preferred are the following known compounds, the compounds listed in Table 1 to Table 78, the compounds described in the examples, and non-toxic salts of these compounds.
[524] In the following table, 3-Py represents a pyridin-3-yl group, Me represents a methyl group, Et represents an ethyl group, n-Pr represents an n-propyl group, i-Pr represents an isopropyl group, t -Bu represents a t-butyl group, and other symbols have the same meanings as described above.
[525]
[526] [Production method of the compound of the present invention]
[527] The compound of the present invention represented by the formula (I) can be produced by the following method or the method described in the examples.
[528] Among the compounds of the present invention represented by the formula (I), the compound of the present invention represented by the following formula (I-1) can be produced by a known method or by the following methods [1] to [14].
[529]
[530] In the above formulas, all symbols have the same meanings as defined above.
[531] [1] Among the compounds of the present invention represented by the formula (I-1), the compound of the present invention in which n represents 1 or 2 can be produced by the following methods (a) to (b).
[532] (a) a compound of the present invention represented by the formula (I-1) wherein n represents 1, that is, a compound of the present invention represented by the following formula (I-1-1a) Followed by an oxidation reaction.
[533]
[534] In the above formulas, all symbols have the same meanings as defined above.
[535]
[536] In the above formulas, all symbols have the same meanings as defined above.
[537] This oxidation reaction is known and can be carried out, for example, by reacting 1 to 1.2 equivalents of an oxidizing agent (hydrogen peroxide, sodium periodate, sodium nitrite, sodium perborate) in an appropriate organic solvent (methylene chloride, chloroform, benzene, hexane, At a temperature of -40 to 0 占 폚 in the presence of a base (e.g., 3-chloro-benzoic acid, peracetic acid, etc.), potassium peroxymonosulfate, potassium permanganate, chromic acid and the like.
[538] (b) a compound of the present invention represented by the formula (I-1) wherein n represents 2, that is, a compound of the present invention represented by the following formula (I-1-1b) And the like.
[539]
[540] In the above formulas, all symbols have the same meanings as defined above.
[541] This oxidation reaction is well known and can be carried out, for example, by reacting an excess amount of an oxidizing agent (hydrogen peroxide, sodium periodate, nitrite acylate, sodium perborate, peracetic acid (hydrogen peroxide, etc.) in an appropriate organic solvent (methylene chloride, chloroform, benzene, Such as 3-chloro benzoic acid, peracetic acid, etc., potassium peroxymonosulfate, potassium permanganate, chromic acid and the like) at a temperature of 20 to 60 캜.
[542] [2] In the compound of the present invention represented by the formula (I-1), a compound in which at least one group of R ¹ represents an oxy group substituted with a group containing it, that is, May be produced by the following methods (a) to (b).
[543]
[544] In the above formula, R ^1-1-2 has the same meaning as R ¹ . Provided that at least one of R &lt; ^1-1 &gt; and R &lt; 2 &gt; - 2 is substituted with an oxo group or a group containing it, and other symbols have the same meanings as described above.
[545] (a) the compound of the present invention represented by the general formula (I-1-2) is a compound wherein at least one group of R ¹ represents a hydroxyl group or a group containing it, that is, a compound represented by the general formula (I- Bromine, iodine, mesyl group or tosyl group) by an etherification reaction.
[546]
[547] In the above formula, R ^1-1-2a has the same meaning as R ¹ . Provided that at least one group of R ^1-1-2a represents a hydroxyl group or a group containing it, and the other symbols have the same meanings as defined above.
[548] This etherification reaction is known and can be carried out, for example, by reacting a hydroxide of an alkali metal (such as sodium hydroxide, potassium hydroxide, lithium hydroxide or the like) in an inert organic solvent (dimethylformamide, dimethylsulfoxide, chloroform, methylene chloride, diethyl ether, tetrahydrofuran, (Barium hydroxide, calcium hydroxide, etc.) or a carbonate (sodium carbonate, potassium carbonate, etc.) or an aqueous solution thereof or a mixture thereof at 0 to 100 占 폚.
[549] (b) The compound of the present invention represented by the general formula (I-1-2) is a compound wherein at least one group of R ¹ represents a hydroxyl group or a group containing the same, that is, And then subjecting the compound to an etherification reaction.
[550]
[551] In the above formula, R ^1-1-2b has the same meaning as R ¹ . Provided that at least one group of R ^1-1-2b represents a hydroxyl group or a group containing it, and the other symbols have the same meanings as defined above.
[552] This etherification reaction is well known and can be carried out, for example, in an organic solvent (dichloromethane, diethyl ether, tetrahydrofuran, acetonitrile, benzene, toluene etc.) with an azo compound (diethyl azodicarboxylate, diisostearoyl azodicarboxylate (N, N-dimethylformamide), and phosphine compounds (triphenylphosphine, tributylphosphine, tributylphosphine, tributylphosphine, Trimethylphosphine or the like) at 0 to &lt; RTI ID = 0.0 &gt; 60 C. &lt; / RTI &gt;
[553] [3] The compound of the present invention represented by the formula (I-1) wherein the amino group substituted with at least one group of R ¹ or a group containing the same, that is, the compound of the present invention represented by the following formula (a) to (d).
[554]
[555] In the above formula, R ^1-1-3 has the same meaning as R ¹ . Provided that at least one of R &lt; ^1-1-3 &gt; is an amino group substituted with a group or a group containing it, and other symbols have the same meanings as defined above.
[556] (a) The compound of the present invention represented by the general formula (I-1-3) is a compound wherein at least one group of R ¹ represents a halogen atom (chlorine, bromine or iodine) Can be prepared by reacting the compound to be displayed with the corresponding compound having an amino group.
[557]
[558] In the above formula, R ^1-1-3a has the same meaning as R ¹ . Provided that at least one group of R ^1-1-3a represents a halogen atom (chlorine, bromine, iodine) or a group containing it, and other symbols have the same meanings as defined above.
[559] This reaction is known and can be carried out in the presence of a base such as triethylamine or pyridine in an inert organic solvent (dimethylformamide, dimethylsulfoxide, chloroform, methylene chloride, diethyl ether, tetrahydrofuran, acetonitrile etc.) Lt; RTI ID = 0.0 &gt; 0-100 C. &lt; / RTI &gt;
[560] (b) The compound of the present invention represented by the general formula (I-1-3) can be produced by reacting a compound represented by the general formula (I-1-3b) wherein at least one group of R ¹ represents an amino group or a group containing it, Chlorine, bromine, iodine) in the presence of a base.
[561]
[562] In the above formula, R ^1-1-3b has the same meaning as R ¹ , but at least one of R ^1-1-3b represents an amino group or a group containing it, and other symbols have the same meanings as described above.
[563] This reaction can be carried out in the same manner as the preparation of the compound represented by the above general formula (I-1-3).
[564] (c) The compound of the present invention represented by the general formula (I-1-3) is obtained by reacting a compound represented by the general formula (I-1-3c) wherein at least one group of R ¹ represents an amino group or a group containing it, And then subjecting the compound to a reductive amination reaction.
[565]
[566] In the above formula, R ^1-1-3c has the same meaning as R ¹ , but at least one of R ^1-1-3c represents an amino group or a group containing it, and the other symbols have the same meanings as defined above.
[567] This reductive amination reaction is known and can be carried out, for example, by reacting a reducing agent (such as sodium cyanoborohydride, sodium triacetoxyborohydride, sodium borohydride, palladium (III) chloride or the like) in an organic solvent (methanol, ethanol, dimethylformamide, dimethylsulfoxide, -Carbon, etc.) and optionally in the presence of an acid (acetic acid, aqueous hydrochloric acid, etc.) at -20 to 60 占 폚.
[568] (d) The compound of the present invention represented by the general formula (I-1-3) is a compound represented by the general formula (I-1-3) in which at least one group of R ¹ represents a carbonyl group or a group containing it, And then subjecting the compound to a reductive amination reaction.
[569]
[570] In the above formula, R ^1-1-3d has the same meaning as R ¹ , but at least one of R ^1-1-3d represents a carbonyl group or a group containing it, and the other symbols have the same meanings as defined above.
[571] This reductive amination reaction can be carried out in the same manner as the preparation of the compound represented by the above general formula (I-1-3c).
[572] [4] The compound of the present invention represented by the formula (I-1) wherein at least one group of R ¹ represents an amide group or a group containing the same, that is, may be prepared by the methods of a) to b).
[573]
[574] In the above formula, R ^1-1-4 has the same meaning as R ¹ . Provided that at least one of R &lt; ^1-1-4 &gt; represents an amide group or a group containing it, and other symbols have the same meanings as defined above.
[575] (a) The compound of the present invention represented by the general formula (I-1-4) is a compound wherein at least one group of R ¹ represents a -COOH group or a group containing it, that is, a compound represented by the following general formula Can be prepared by amidation reaction.
[576]
[577] In the above formula, R ^1-1-4a has the same meaning as R ¹ . Provided that at least one group of R ^1-1-4a represents a -COOH group or a group containing it, and the other symbols have the same meanings as defined above.
[578] This amidation reaction is known, and examples thereof include the following methods.
[579] 1) Method using acid halide
[580] 2) Method using mixed acid anhydride
[581] 3) a method using a condensing agent,
[582] Describing these methods in detail,
[583] The method using 1) an acid halide can be carried out, for example, by reacting a carboxylic acid with an acid halide (oxalyl chloride, thionyl chloride or the like) in an inert organic solvent (chloroform, methylene chloride, diethyl ether, tetrahydrofuran, And the resulting acid halide is reacted with an amine in an inert organic solvent (chloroform, methylene chloride, chloroform, dichloromethane, etc.) in the presence of a tertiary amine (pyridine, triethylamine, dimethylaniline, dimethylaminopyridine, etc.) Diethyl ether, tetrahydrofuran and the like) at 0 to 40 ° C.
[584] 2) The method using the mixed acid anhydride can be carried out, for example, by reacting the carboxylic acid with a tertiary amine (eg, pyridine, triethylamine, dimethyl (trimethylsilyl) amide) in an inert organic solvent (chloroform, methylene chloride, diethyl ether, tetrahydrofuran, (Pivaloyl chloride, tosyl chloride, mesyl chloride, etc.) or an acid derivative (such as ethyl chloroformate or isobutyl chloroformate) at 0 to 40 ° C in the presence of a base (for example, aniline, dimethylaminopyridine, etc.) Is carried out by reacting an acid anhydride with an amine in an inert organic solvent (chloroform, methylene chloride, diethyl ether, tetrahydrofuran, etc.) at 0 to 40 ° C.
[585] 3) The method using a condensing agent can be carried out, for example, by reacting a carboxylic acid and an amine in the presence or absence of a tertiary amine (pyridine, triethyl (trimethylsilyl) amide) in an organic solvent (chloroform, methylene chloride, dimethylformamide, diethyl ether, tetrahydrofuran, Ethylcyclohexylcarbodiimide (DCC), 1-ethyl-3- [3- (dimethylamino) propyl] carbamate or the like in the presence or in the absence of a condensing agent (amine, dimethyl aniline, dimethylaminopyridine, 1-hydroxybenzotriazole (HOBt) is prepared by using EDC, 1,1'-carbonyldiimidazole (CDI), 2-chloro-1-methylpyridinium iodide, propane phosphoric acid cyclic anhydride, At 0 to &lt; RTI ID = 0.0 &gt; 40 C. &lt; / RTI &gt;
[586] The reactions of 1), 2) and 3) are preferably performed under an anhydrous condition in an atmosphere of inert gas (argon, nitrogen, etc.).
[587] (b) The compound of the present invention represented by the formula (I-1-4) is a compound wherein at least one group of R ¹ represents an amino group or a group containing it, that is, a compound having a carboxyl group Can be prepared by amidation reaction of the compound.
[588]
[589] In the above formula, R ^1-1-4b has the same meaning as R ¹ . Provided that at least one group of R ^1-1-4b represents an amino group or a group containing it, and the other symbols have the same meanings as defined above.
[590] The amidation reaction can be carried out in the same manner as the preparation of the compound represented by the above formula (I-1-4a).
[591] [5] The compound of the present invention represented by the formula (I-1) wherein at least one group represented by R ¹ represents an ester group or a group containing the ester group, that is, may be prepared by the methods of a) to b).
[592]
[593] In the above formula, R ^1-1-5 has the same meaning as R ¹ . Provided that at least one of R &lt; ^1-1 &gt; to R &lt; 5 &gt; represents an ester group or a group containing the ester group, and other symbols have the same meanings as described above.
[594] (a) The compound of the present invention represented by the general formula (I-1-5) is a compound wherein at least one group of R ¹ represents a -COOH group or a group containing a group containing it, that is, a compound represented by the following general formula Can be prepared by esterification reaction of the corresponding compound.
[595]
[596] In the above formula, R ^1-1-5a has the same meaning as R ¹ . Provided that at least one group of R ^1-1-5a represents a -COOH group or a group containing it, and the other symbols have the same meanings as defined above.
[597] This esterification reaction is known, and for example, the following method and the like can be mentioned.
[598] 1) Method using acid halide
[599] 2) Method using mixed acid anhydride
[600] 3) A method using a condensing agent.
[601] Describing these methods in detail,
[602] The method using 1) an acid halide can be carried out, for example, by reacting a carboxylic acid with an acid halide (such as oxalyl chloride, thionyl chloride, etc.) in an inert organic solvent (chloroform, methylene chloride, diethyl ether, tetrahydrofuran, In the presence of a tertiary amine (pyridine, triethylamine, dimethylaniline, dimethylaminopyridine, etc.) in an inert organic solvent (chloroform, methylene chloride, diethyl Ether, tetrahydrofuran and the like) at 0 to 40 ° C.
[603] 2) The method using the mixed acid anhydride can be carried out, for example, by reacting the carboxylic acid with a tertiary amine (eg, pyridine, triethylamine, dimethyl (trimethylsilyl) amide) in an inert organic solvent (chloroform, methylene chloride, diethyl ether, tetrahydrofuran, (Such as pivaloyl chloride, tosyl chloride or mesyl chloride) or an acid derivative (such as ethyl chloroformate or isobutyl chloroformate) in the presence of a base (e.g., aniline, dimethylaminopyridine, etc.) The reaction is carried out by reacting the mixed acid anhydride with an alcohol in an inert organic solvent (chloroform, methylene chloride, diethyl ether, tetrahydrofuran, etc.) at 0 to 40 ° C.
[604] 3) The method using a condensing agent can be carried out, for example, by reacting a carboxylic acid and an alcohol in the presence or absence of a tertiary amine (pyridine, triethyl (trimethylsilyl) amide) in an organic solvent (chloroform, methylene chloride, dimethylformamide, diethyl ether, tetrahydrofuran, Ethylcyclohexylcarbodiimide (DCC), 1-ethyl-3- [3- (dimethylamino) propyl] carbamate or the like in the presence or in the absence of a condensing agent (amine, dimethyl aniline, dimethylaminopyridine, 1-hydroxybenzotriazole (HOBt) is prepared by using EDC, 1,1'-carbonyldiimidazole (CDI), 2-chloro-1-methylpyridinium iodide, propane phosphoric acid cyclic anhydride, At 0 to &lt; RTI ID = 0.0 &gt; 40 C. &lt; / RTI &gt;
[605] It is preferable that all of the reactions of 1), 2) and 3) are carried out under an anhydrous condition under an inert gas (argon, nitrogen, etc.) atmosphere.
[606] (b) The compound of the present invention represented by the formula (I-1-5) is a compound wherein at least one group of R ¹ is a hydroxyl group or a compound having a group containing it, that is, And then subjecting the compound to an esterification reaction.
[607]
[608] In the above formula, R ^1-1-5b has the same meaning as R ¹ . Provided that at least one group of R ^1-1-5b represents a hydroxyl group or a group containing it, and the other symbols have the same meanings as defined above.
[609] The esterification reaction can be carried out in the same manner as in the production of the compound represented by the above general formula (I-1-5a).
[610] [6] The compound of the present invention represented by the formula (I-1) wherein at least one group of R ¹ represents a sulfonamide group or a group containing the same, that is, (a) to (b).
[611]
[612] In the above formula, R ^1-1-6 has the same meaning as R ¹ . Provided that at least one of R &lt; ^1-1-6 &gt; represents a sulfonamide group or a group containing it, and other symbols have the same meanings as defined above.
[613] (a) The compound of the present invention represented by the general formula (I-1-6) is a compound represented by the general formula (II) wherein at least one group of R ¹ represents a group represented by -SO ₃ H or a group containing the same, that is, Can be prepared by subjecting a compound to a sulfonamidation reaction.
[614]
[615] In the above formula, R ^1-1-6a has the same meaning as R ¹ . Provided that at least one group of R ^1-1-6a represents an -SO ₃ H group or a group containing it, and other symbols have the same meanings as defined above.
[616] Sulfonamidation reaction is known, for example, by reacting a sulfonic acid with an acid halide (oxalyl chloride, thionyl chloride, etc.) in an inert organic solvent (chloroform, methylene chloride, diethyl ether, tetrahydrofuran, The halogenated compound obtained by the reaction at a temperature of 20 ° C to reflux temperature is reacted with an amine in an inert organic solvent (chloroform, methylene chloride, diethyl ether, tetrahydrofuran, etc.) in the presence of a tertiary amine (pyridine, triethylamine, dimethylaniline, dimethylaminopyridine, etc.) ) At 0 to &lt; RTI ID = 0.0 &gt; 40 C. &lt; / RTI &gt;
[617] (b) The compound of the present invention represented by the general formula (I-1-6) is a compound wherein at least one group of R ¹ represents an amino group or a group containing it, that is, a compound having a sulfo group And then subjecting the compound to a sulfonamidation reaction.
[618]
[619] In the above formula, R ^1-1-6b has the same meaning as R ¹ . Provided that at least one group of R ^1-1-6b represents an amino group or a group containing it, and other symbols have the same meanings as defined above.
[620] The sulfonamidation reaction can be carried out in the same manner as the preparation of the compound represented by the above general formula (I-1-6a).
[621] [7] In the compound of the present invention represented by the formula (I-1), at least one group of R ¹ is substituted with an aminocarbonyloxy group or a compound having a group containing it, that is, The compound may be produced by reacting a compound represented by the formula (I-1-7a) shown below and a corresponding compound having an isocyanate group, in which at least one of the groups represented by R ¹ represents a hydroxyl group or a group containing the hydroxyl group.
[622]
[623] In the above formula, R ^1-1-7 has the same meaning as R ¹ . Provided that at least one group of R ^1-1-7 is substituted with an aminocarbonyloxy group or a group containing it, and the other symbols have the same meanings as defined above.
[624]
[625] In the above formula, R ^1-1-7a has the same meaning as R ¹ . Provided that at least one group of R ^1-1-7a represents a hydroxyl group or a group containing it, and other symbols have the same meanings as defined above.
[626] This reaction is known, and for example, the reaction can be carried out in the presence of a base (1,8-diazabicyclo [5.4.0] undec-7-ene (DBU), tri Ethylamine, sodium hydride and the like) at 0 to 100 ° C.
[627] [8] A compound of the present invention represented by the formula (I-1) wherein at least one group of R ¹ is substituted or an amino-carbonylamino group substituted with a group containing the same, that is, May be prepared by reacting at least one group of R &lt; ¹ &gt; with an amino group or a compound having a group containing it, i.e., a compound represented by the following general formula (I-1-8a) and a corresponding compound having an isocyanate group.
[628]
[629] In the above formula, R ^1-1-8 has the same meaning as R ¹ . With the proviso that at least one group of R ^1-1-8 is substituted with an aminocarbonylamino group or a group containing it, and the other symbols have the same meanings as defined above.
[630]
[631] In the above formula, R ^1-1-8a has the same meaning as R ¹ . Provided that at least one group of R ^1-1-8a represents an amino group or a group containing it, and the other symbols have the same meanings as defined above.
[632] This reaction can be carried out in the same manner as the preparation of the compound represented by the above general formula (I-1-7).
[633] [9] A compound represented by the formula (I-1) in which at least one group of R ¹ is substituted with an oxycarbonylamino group or a group containing the same, that is, a compound of the present invention represented by the following formula May be prepared by reacting a compound in which at least one group of R &lt; ¹ &gt; is an amino group or a group containing it, i.e., a compound represented by the following general formula (I-1-9a) and the corresponding haloformic acid ester.
[634]
[635] In the above formula, R ^1-1-9 has the same meaning as R ¹ . Provided that at least one of R &lt; ^1-1-9 &gt; is an oxycarbonylamino group substituted with a group or a group containing it, and other symbols have the same meanings as defined above.
[636]
[637] In the above formula, R ^1-1-9a has the same meaning as R ¹ . Provided that at least one group of R ^1-1-9a represents an amino group or a group containing it, and the other symbols have the same meanings as defined above.
[638] This reaction is known and is carried out, for example, by reacting in an organic solvent (tetrahydrofuran, methylene chloride, diethyl ether, etc.) in the presence of a base (triethylamine, pyridine, etc.) at -78 to 40 ° C.
[639] [10] The oxycarbonyloxy group substituted with at least one group of R ¹ in the compound of the present invention represented by the general formula (I-1) or a compound having the group containing the same, that is, The compound can also be produced by reacting a compound in which at least one group of R ¹ represents a hydroxyl group or a group containing it, that is, a compound represented by the following formula (I-1-10a) and the corresponding haloformic acid ester.
[640]
[641] In the above formula, R ^1-1-10 has the same meaning as R ¹ . Provided that at least one of R &lt; ^1-10 &gt; is an oxycarbonyloxy group substituted with a group or a group containing it, and other symbols have the same meanings as defined above.
[642]
[643] In the above formula, R ^1-1-10a has the same meaning as R ¹ . Provided that at least one group of R ^1-1-10a represents a hydroxyl group or a group containing it, and the other symbols have the same meanings as defined above.
[644] This reaction can be carried out in the same manner as the preparation of the compound represented by the above general formula (I-1-9).
[645] [11] The compound of the present invention represented by the formula (I-1) wherein at least one group of R ¹ represents a substituted (hydroxy) methyl group or a group containing the same, The compound can also be produced by the following methods (a) to (b).
[646]
[647] In the above formula, R ^1-1-11 has the same meaning as R ¹ . With the proviso that at least one of R &lt; ^1-11 &gt; is a substituted (hydroxy) methyl group or a group containing it, and other symbols have the same meanings as defined above.
[648] (a) a compound of the present invention represented by the formula (I-1-11) wherein n represents 0, that is, a compound of the present invention represented by the formula (I-1-11a), wherein at least one group of R ¹ represents a formyl group , That is, a compound represented by the general formula (I-1-11aa) and the corresponding Grignard reagent or a corresponding derivative having lithium.
[649]
[650] In the above formulas, all symbols have the same meanings as defined above.
[651]
[652] In the above formula, R ^1-1-11a has the same meaning as R ¹ . Provided that at least one group of R ^1-1-11a represents a formyl group and the other symbols have the same meanings as defined above.
[653] This reaction is known and is carried out, for example, in an organic solvent (tetrahydrofuran, diethyl ether, etc.) at -78 to 0 캜.
[654] (b) a compound of the present invention represented by the formula (I-1-11) wherein n represents 1 or 2, that is, the compound of the present invention represented by the formula (I-1-11b) Is subjected to the oxidation reaction of the above-mentioned [1].
[655]
[656] N-1-11b in the above formula represents an integer of 1 to 2, and other symbols have the same meanings as defined above.
[657] [12] The compound of the present invention represented by the formula (I-1) wherein the carbonyl group substituted with at least one group of R ¹ or a group containing the same, that is, Can be prepared by subjecting the compound represented by I-1-11 to an oxidation reaction.
[658]
[659] In the above formula, R ^1-1-12 represents the same meaning as R ¹ . Provided that at least one of R &lt; ^1-1 &gt; to R &lt; ¹² &gt; is a substituted carbonyl group or a group containing it, and other symbols have the same meanings as defined above.
[660] This oxidation reaction is known and is carried out, for example, by reacting with an oxidizing agent (manganese dioxide, oxalyl chloride, pyridinium dichromate, etc.) in an organic solvent (methylene chloride, chloroform, etc.) at -78 to 40 ° C.
[661] [13] The compound in the present invention represents a compound represented by the general formula (I-1) at least one group of R ¹ containing an amino group or it, that is, at least one of the present compounds represented by the general formula I R ¹ is-1-13 Or a compound containing a group containing it, that is, the compound represented by the general formula (I-1-13a) can be produced by a nitro group reduction reaction.
[662]
[663] In the above formula, R ^1-1-13 has the same meaning as R ¹ . With the proviso that at least one group of R ^1-1 to R ¹³ represents an amino group or a group containing the same and the other symbols have the same meanings as defined above.
[664]
[665] In the above formula, R ^1-1-13a has the same meaning as R ¹ . Provided that at least one group of R ^1-1-13a represents a nitro group or a group containing it, and the other symbols have the same meanings as defined above.
[666] The reduction reaction of the nitro group is known, and is carried out, for example, by a hydrolysis and a reduction reaction using an organic metal.
[667] This hydrolytic decomposition reaction is well known and includes, for example, an inert solvent [ether type (e.g., tetrahydrofuran, dioxane, dimethoxyethane, diethyl ether, etc.), alcohol (e.g., methanol, ethanol, , Acetone, methyl ethyl ketone, etc.), nitrile (such as acetonitrile), amide (such as dimethylformamide), water, ethyl acetate, (Such as hydrochloric acid, sulfuric acid, phosphoric acid, etc.) in the presence of a hydrogenation catalyst (for example, palladium-carbon, palladium black, palladium, palladium hydroxide, platinum dioxide, nickel, Raney- In the presence or absence of an organic acid (e.g., acetic acid, p-toluenesulfonic acid, oxalic acid, trifluoroacetic acid, formic acid, etc.) under atmospheric pressure or under a hydrogen atmosphere or Under reumsan ammonium present it is carried out at a temperature of 0~200 ℃. When an acid is used, a salt thereof may be used.
[668] The reduction reaction using an organometallic compound is well known and can be carried out by using an organic metal (zinc, iron, tin, tin chloride, or ferric chloride) in a solvent (ethanol, methanol or the like) that is miscible with water in the presence or absence of an aqueous hydrochloric acid solution Lt; RTI ID = 0.0 &gt; 50 C &lt; / RTI &gt;
[669] [14] In the compound of the present invention represented by the formula (I-1), at least one group of R ¹ is a -COOH group or a group containing it, a hydroxyl group or a group containing it or an amino group or a group containing it, The compound of the present invention represented by the formula I-1-14 is a compound in which the -COOH group, the hydroxyl group, the amino group or the group containing them in the compound represented by the formula (I-1) Can also be produced by alkaline hydrolysis, deprotection reaction under acidic conditions, deprotection reaction of silyl group or deprotection reaction by hydrogenolysis.
[670]
[671] In the above formula, R ^1-1-14 has the same meaning as R ¹ . Provided that at least one group of R ^1-14 represents a -COOH group, a hydroxyl group or an amino group or a group containing them, and other symbols have the same meanings as defined above.
[672]
[673] In the above formula, R ^1-1-14a has the same meaning as R ¹ . Provided that at least one of R ^1-1 to R ^14a is protected with a -COOH group such as a methyl group, an ethyl group, a t-butyl group and a benzyl group, a protected hydroxyl group such as a methoxymethyl group, (Such as a benzyloxycarbonyl group, a t-butoxycarbonyloxy group, a trifluoroacetyl group, etc.) which is protected by a protecting group such as a benzyloxycarbonyl group, Or a group containing them, and the other symbols have the same meanings as defined above.
[674] The deprotection reaction by alkaline hydrolysis is known, and examples thereof include hydroxides of alkali metals (sodium hydroxide, potassium hydroxide, lithium hydroxide and the like), hydroxides of alkaline earth metals (Barium hydroxide, calcium hydroxide, etc.) or a carbonate (sodium carbonate, potassium carbonate, etc.), an aqueous solution thereof, or a mixture thereof.
[675] The deprotection reaction under acidic conditions is well known and can be carried out, for example, by reacting an organic acid (acetic acid, trifluoroacetic acid, methanesulfonic acid, iodomethyltrimethylsilyl, etc.) or an organic acid (Hydrochloric acid, sulfuric acid, etc.) or a mixture thereof (e.g., hydrogen bromide acetic acid) at a temperature of 0 to 100 캜.
[676] The deprotection reaction of the silyl group is well known and is carried out, for example, in an organic solvent (tetrahydrofuran, acetonitrile, etc.) which can be mixed with water at a temperature of 0 to 40 캜 using tetrabutylammonium fluoride.
[677] The deprotection reaction by hydrolysis is carried out in the same manner as the hydrolysis reaction described in [13].
[678] Among the compounds represented by the formula (I), the compounds represented by the following formula (I-2) can be produced by the following methods [15] to [17].
[679]
[680] The compound of the present invention represented by the formula (I-2) wherein m represents 0, that is, the compound of the present invention represented by the following formula (I-2-15) . &Lt; / RTI &gt;
[681]
[682] In the above formulas, all symbols have the same meanings as defined above.
[683] (a) a compound of the present invention represented by the formula (I-2-15) wherein n represents 1 or 2, that is, the compound of the present invention represented by the formula (I-2-15a) Can be prepared by reacting a compound represented by the formula (I-1-1b) with a compound represented by the following formula (III).
[684]
[685] In the above formula, n-2-15a represents an integer of 1 to 2, and the other symbols have the same meanings as defined above.
[686]
[687] In the above formulas, all symbols have the same meanings as defined above.
[688] This reaction is well known in the art (see J. Am. Chem. Soc. , 72 , 1985 (1950), J. Org. Chem. , 54 , 4232 A hydride of an alkali metal, a hydroxide of an alkali metal (such as sodium hydroxide, potassium hydroxide, or lithium hydroxide), an alkaline earth metal (such as sodium hydroxide, potassium hydroxide or the like), an alkaline earth metal (Barium hydroxide, calcium hydroxide, etc.) or a tertiary amine (pyridine, triethylamine, dimethylaniline, dimethylaminopyridine, etc.) or an aqueous solution thereof or a mixture thereof at a temperature of 0 to 40 占 폚.
[689] (b) Compounds of the present invention represented by the formula (I-2-15) wherein n represents 0, that is, the compounds of the present invention represented by the formula (I-2-15b) And n is 1, that is, a compound represented by the following formula (I-2-15ab) can be produced by a reduction reaction.
[690]
[691] In the above formulas, all symbols have the same meanings as defined above.
[692]
[693] In the above formulas, all symbols have the same meanings as defined above.
[694] This reduction reaction is known and is carried out, for example, by reacting with an organic solvent (diethyl ether, tetrahydrofuran, etc.) and a reducing agent (lithium aluminum hydride, diisobutyl aluminum hydride, etc.) at a temperature of 0 to 80 캜.
[695] [16] The compound of the present invention represented by the formula (I-2) wherein m is 1, that is, the compound of the formula (I-2-16) Followed by an oxidation reaction.
[696]
[697] In the above formulas, all symbols have the same meanings as defined above.
[698] This oxidation reaction can be carried out in the same manner as in the production of the compound represented by the general formula (I-1-1a) described in [1].
[699] The compound of the present invention represented by the formula (I-2) wherein m represents 2, that is, the compound of the present invention represented by the following formula (I-2-17) . &Lt; / RTI &gt;
[700]
[701] In the above formulas, all symbols have the same meanings as defined above.
[702] (a) a compound of the present invention represented by the formula (I-2-17) wherein n represents 1 or 2, that is, the compound of the present invention represented by the formula (I-2-17a) Can be prepared by reacting a compound represented by the formula (I-1-1b) with a compound represented by the following formula (IV).
[703]
[704] In the above formula, n-2-17a represents an integer of 1 to 2, and other symbols have the same meanings as defined above.
[705]
[706] In the above formulas, all symbols have the same meanings as defined above.
[707] This reaction is carried out by a method such as the reaction of the compound represented by the general formula (I-2-15a) and the compound represented by the general formula (III) described in [15].
[708] (b) Compounds of the present invention represented by the formula (I-2-17) wherein n represents 0, that is, the compounds represented by the following formula (I-2-17b) can be prepared by reducing a compound represented by the formula can do.
[709]
[710] In the above formulas, all symbols have the same meanings as defined above.
[711] Formula V
[712]
[713] In the above formulas, all symbols have the same meanings as defined above.
[714] This reduction reaction is known and is carried out, for example, by a hydrogenation reaction or a reduction reaction using triethylsilane.
[715] This hydrogenation reaction is known and can be carried out, for example, in an inert solvent [ether type (e.g., tetrahydrofuran, dioxane, dimethoxyethane, diethyl ether, etc.), alcohol type (e.g., methanol, ethanol, (Such as benzene, toluene, etc.), ketones (e.g., acetone, methyl ethyl ketone, etc.), nitriles (e.g. acetonitrile etc.), amides such as dimethylformamide, water, ethyl acetate, (Such as hydrochloric acid, sulfuric acid, hypochlorous acid, etc.) in the presence of a hydrogenation catalyst (for example, palladium-carbon, palladium black, palladium, palladium hydroxide, platinum dioxide, nickel, In the presence or absence of an organic acid (e.g., acetic acid, p-toluenesulfonic acid, oxalic acid, trifluoroacetic acid, formic acid, etc.) under atmospheric pressure or under a hydrogen atmosphere Lt; RTI ID = 0.0 &gt; 0 C &lt; / RTI &gt; in the presence of ammonium formate. When an acid is used, a salt thereof may be used.
[716] This reduction reaction using triethylsilane is known and is carried out, for example, in trifluoroacetic acid at a temperature of 0 to 100 DEG C in the presence of triethylsilane.
[717] (c) The compound of the present invention represented by the formula (I-2-17) wherein n represents 2, that is, the compound of the present invention represented by the following formula (I-2-17c) , And n represents 2, that is, a compound represented by the following general formula (I-2-15ac).
[718]
[719] In the above formulas, all symbols have the same meanings as defined above.
[720]
[721] In the above formulas, all symbols have the same meanings as defined above.
[722] This oxidation reaction can be carried out in the same manner as in the method for producing the compound represented by the general formula (I-1-1b) described in [1].
[723] The compound of the present invention represented by the formula (I-2) can be produced by the following methods [18] to [30] in addition to the methods of [15] to [17].
[724] [18] Among the compounds of the present invention represented by the formula (I-2), compounds in which at least one group of R ¹ or R ² represents an oxy group substituted with a group containing it, The inventive compounds can also be prepared by the following methods (a) to (b).
[725]
[726] In the above formulas, R ^1-2-18 and R ^2-2-18 have the same meanings as R ¹ and R ² . With the proviso that at least one group of R ^1-2-18 and R ^2-2-18 represents a substituted oxy group or a group containing it, and the other symbols have the same meanings as defined above.
[727] (a) The compound of the present invention represented by the general formula (I-2-18) is a compound wherein at least one of R ¹ or R ² represents a hydroxyl group or a group containing it, that is, a compound represented by the following general formula (Such as chlorine, bromine, iodine, mesyl or tosyl group) by etherification reaction.
[728]
[729] In the above formula, R ^1-2-18a and R ^2-2-18a have the same meanings as R ¹ and R ² . Provided that at least one group of R ^1-2-18a and R ^2-2-18a represents a hydroxyl group or a group containing it, and the other symbols have the same meanings as defined above.
[730] This etherification reaction can be carried out in the same manner as the method for producing the compound represented by the general formula (I-1-2a) described in [2].
[731] (b) The compound of the present invention represented by the general formula (I-2-18) is a compound wherein at least one group of R ¹ represents a hydroxyl group or a group containing it, that is, a compound having a hydroxyl group The compound can also be prepared by etherification.
[732]
[733] In the above formula, R ^1-2-18b and R ^2-2-18b have the same meanings as R ¹ and R ² . Provided that at least one of R ^1-2-18b and R ^2-2-18b represents a hydroxyl group or a group containing it, and the other symbols have the same meanings as defined above.
[734] This etherification reaction can be carried out in the same manner as the method for producing the compound represented by the general formula (I-1-2b) described in [2].
[735] Among the compounds of the present invention represented by the formula (I-2), compounds in which at least one group of R ¹ or R ² represents an amino group substituted with an amino group or a group containing the amino group, The compound can also be prepared by the following methods (a) to (d).
[736]
[737] In the above formulas, R ^1-2-19 and R ^2-2-19 have the same meanings as R ¹ and R ² . With the proviso that at least one of R ^1-2-19 and R ^2-2-19 represents an amino group substituted with a group or a group containing it, and the other symbols have the same meanings as defined above.
[738] (a) the compound of the present invention represented by the general formula (I-2-19) is a compound represented by the general formula (I- ²⁾ : wherein R ¹ or R ² represents a halogen atom (chlorine, bromine, iodine) -19a with a corresponding compound having an amino group.
[739]
[740] In the above formulas, R ^1-2-19a and R ^2-2-19a have the same meanings as R ¹ and R ² . Provided that at least one group of R ^1-2-19a and R ^2-2-19a represents a halogen atom (chlorine, bromine, iodine) or a group containing it, and the other symbols have the same meanings as defined above.
[741] This reaction can be carried out in the same manner as in the production of the compound represented by the general formula (I-1-3) described in [3].
[742] (b) The compound of the present invention represented by the formula (I-2-19) is a compound wherein at least one group of R ¹ or R ² represents an amino group or a group containing it, that is, May be prepared by reacting the corresponding compound having a halogen atom (chlorine, bromine, iodine).
[743]
[744] In the above formulas, R ^1-2-19b and R ^2-2-19b have the same meanings as R ¹ and R ² , but at least one group of R ^1-2-19b and R ^2-2-19b is an amino group or a And the other symbols have the same meanings as defined above.
[745] This reaction can be carried out in the same manner as in the production of the compound represented by the general formula (I-1-3) described in [3].
[746] (c) The compound of the present invention represented by the general formula (I-2-19) is a compound represented by the general formula (I-2-19c) wherein at least one group of R ¹ or R ² represents an amino group or a group containing the amino group, May be prepared by reacting the corresponding compound having a carbonyl group.
[747]
[748] In the above formulas, R ^1-2-19c and R ^2-2-19c have the same meanings as R ¹ and R ² , but at least one group of R ^1-2-19c and R ^2-2-19c is an amino group or a And the other symbols have the same meanings as defined above.
[749] This reaction can be carried out in the same manner as in the production of the compound represented by the general formula (I-1-3c) described in [3].
[750] (d) The compound of the present invention represented by the general formula (I-2-19) is a compound wherein at least one group of R ¹ or R ¹ represents a carbonyl group or a group containing it, And then subjecting the corresponding compound having an amino group to a reductive amination reaction.
[751]
[752] In the above formulas, R ^1-2-19d and R ^2-2-19d have the same meanings as R ¹ and R ² , but at least one group of R ^1-2-19d and R ^2-2-19d is a carbonyl group or a And the other symbols have the same meanings as defined above.
[753] This reductive amination reaction can be carried out in the same manner as in the production of the compound represented by the general formula (I-1-3c) described in [3].
[754] [20] A compound of the present invention represented by the formula (I-2) wherein at least one group of R ¹ or R ² represents an amide group or a group containing the same, that is, a compound of the present invention represented by the following formula Can also be produced by the following methods (a) to (b).
[755]
[756] In the above formulas, R ^1-2-20 and R ^2-2-20 have the same meanings as R ¹ and R ² . With the proviso that at least one group of R ^1-2-20 and R ^2-2-20 represents an amide group or a group containing it, and the other symbols have the same meanings as defined above.
[757] (a) The compound of the present invention represented by the general formula (I-2-20) is a compound wherein at least one group of R ¹ or R ² represents a -COOH group or a group containing it, that is, a compound represented by the following general formula And the corresponding compound having an amino group can be prepared by amidation reaction.
[758]
[759] In the above formula, R ^1-2-20a and R ^2-2-20a have the same meanings as R ¹ and R ² . Provided that at least one group of R ^1-2-20a and R ^2-2-20a represents a -COOH group or a group containing it, and the other symbols have the same meanings as defined above.
[760] The amidation reaction can be carried out in the same manner as in the production of the compound represented by the general formula (I-1-4) described in [4].
[761] (b) The compound of the present invention represented by the general formula (I-2-20) is a compound wherein at least one group of R ¹ or R ² represents an amino group or a group containing it, that is, a compound represented by the following general formula Can also be prepared by amidation reaction of the corresponding compound having
[762]
[763] In the above formula, R ^1-2-20b and R ^2-2-20b have the same meanings as R ¹ and R ² . Provided that at least one group of R ^1-2-20b and R ^2-2-10b represents an amino group or a group containing it, and the other symbols have the same meanings as defined above.
[764] The amidation reaction can be carried out in the same manner as in the production of the compound represented by the general formula (I-1-4) described in [4].
[765] [21] The compound of the present invention represented by the formula (I-2) wherein at least one of R ¹ or R ² represents an ester group or a group containing the ester group, that is, Can also be produced by the following methods (a) to (b).
[766]
[767] In the above formulas, R ^1-2-21 and R ^2-2-21 have the same meanings as R ¹ and R ² . With the proviso that at least one group of R ^1-2-21 and R ^2-2-21 represents an ester group or a group containing the same and the other symbols have the same meanings as defined above.
[768] (a) The compound of the present invention represented by the formula (I-2-21) is a compound wherein at least one group of R ¹ or R ² represents a -COOH group or a group containing it, that is, a compound represented by the following formula And a corresponding compound having a hydroxyl group can be produced by an esterification reaction.
[769]
[770] In the above formulas, R ^1-2-21a and R ^2-2-21a have the same meanings as R ¹ and R ² . Provided that at least one of R ^1-2-21a and R ^2-2-21a represents a -COOH group or a group containing it, and other symbols have the same meanings as defined above.
[771] This esterification reaction can be carried out in the same manner as in the production of the compound represented by the general formula (I-1-5) described in [5].
[772] (b) The compound of the present invention represented by the general formula (I-2-21) is a compound wherein at least one of R ¹ or R ² represents a hydroxyl group or a group containing it, that is, Can also be prepared by an esterification reaction.
[773]
[774] In the above formulas, R ^1-2-21b and R ^2-2-21b have the same meanings as R ¹ and R ² . Provided that at least one of R ^1-2-21b and R ^2-2-21b represents a hydroxyl group or a group containing it, and the other symbols have the same meanings as defined above.
[775] This esterification reaction can be carried out in the same manner as in the production of the compound represented by the general formula (I-1-5) described in [5].
[776] [22] In the compound of the present invention represented by the formula (I-2), at least one group of R ¹ or R ² represents a sulfonamide group or a group containing the same, that is, The compound can also be prepared by the following methods (a) to (b).
[777]
[778] In the above formula R and R ^{1-2-22 2-2-22} have the same meanings as R ¹ and R ^2. However, R and R ^{1-2-22 2-2-22} represents a group of at least one sulfonamide group, or containing it in, and the other symbols have the same meanings as defined above.
[779] (a) the compound of the present invention represented by the general formula (I-2-22) is a compound wherein at least one group of R ¹ or R ² is a group that represents a group represented by -SO ₃ H or a group containing it, that is, Can also be prepared by subjecting the corresponding compound having a sulfonyl group to a sulfonamidation reaction.
[780]
[781] In the above formulas, R ^1-2-22a and R ^2-2-22a have the same meanings as R ¹ and R ² , provided that at least one group of R ^1-2-22a and R ^2-2-22a is -SO ₃ H group or a group containing it, and other symbols have the same meanings as defined above.
[782] The sulfonamidation reaction can be carried out in the same manner as in the production of the compound represented by the general formula (I-1-6a) described in [6].
[783] (b) The compound of the present invention represented by the general formula (I-2-22) is a compound wherein at least one group of R ¹ or R ² represents an amino group or a group containing it, Can also be prepared by subjecting the corresponding compound having an anion to a sulfonamidation reaction.
[784]
[785] In the above formulas, R ^1-2-22b and R ^2-2-22b have the same meanings as R ¹ and R ² . Provided that at least one group of R ^1-2-22b and R ^2-2-22b represents an amino group or a group containing it, and the other symbols have the same meanings as defined above.
[786] The sulfonamidation reaction can be carried out in the same manner as in the production of the compound represented by the general formula (I-1-6a) described in [6].
[787] Among the compounds of the present invention represented by the formula (I-2), compounds in which at least one group of R ¹ or R ² represents an aminocarbonyloxy group or a group containing a group containing it, The compound of the present invention to be displayed is also prepared by reacting at least one group of R ¹ or R ² with a hydroxyl group or a compound containing it, that is, a compound represented by the following formula (I-2-23a) and a corresponding compound having an isocyanate group .
[788]
[789] In the above formulas, R ^1-2-23 and R ^2-2-23 have the same meanings as R ¹ and R ² . With the proviso that at least one group of R ^1-2-23 and R ^2-2-23 represents an aminocarbonyloxy group substituted with an amino group or a group containing it, and other symbols have the same meanings as defined above.
[790]
[791] In the above formulas, R ^1-2-23a and R ^2-2-23a have the same meanings as R ¹ and R ² . Provided that at least one group of R ^1-2-23a and R ^2-2-23a represents a hydroxyl group or a group containing it, and the other symbols have the same meanings as defined above.
[792] This reaction can be carried out in the same manner as the preparation of the compound represented by the general formula (I-1-7) described in [7].
[793] Among the compounds of the present invention represented by the formula (I-2), compounds in which at least one group of R ¹ or R ² is substituted, or a compound which represents a group containing the same, The compound of the present invention may be prepared by reacting at least one group of R ¹ or R ² with an amino group or a compound containing it, that is, a compound represented by the following formula (I-2-24a) and a corresponding compound having an isocyanate group have.
[794]
[795] In the above formulas, R ^1-2-24 and R ^2-2-24 have the same meanings as R ¹ and R ² . With the proviso that at least one group of R ^1-2-24 and R ^2-2-24 is substituted with an aminocarbonylamino group or a group containing it, and the other symbols have the same meanings as defined above.
[796]
[797] In the above formula, R ^1-2-24a and R ^2-2-24a have the same meanings as R ¹ and R ² . Provided that at least one group of R ^1-2-24a and R ^2-2-24a represents an amino group or a group containing it, and the other symbols have the same meanings as defined above.
[798] This reaction can be carried out in the same manner as the preparation of the compound represented by the general formula (I-1-7) described in [7].
[799] In the compound of the present invention represented by the formula (I-2), the oxycarbonylamino group substituted with at least one group of R ¹ or R ² , or a compound which represents a group containing the same, , The compound of the present invention can also be prepared by reacting a compound in which at least one group of R ¹ or R ² represents an amino group or a group containing it, that is, a compound represented by the following formula (I-2-25a) .
[800]
[801] In the above formulas, R ^1-2-25 and R ^2-2-25 have the same meanings as R ¹ and R ² . Provided that at least one of R ^1-2-25 and R ^2-2-25 is substituted with an oxycarbonylamino group or a group containing the same, and the other symbols have the same meanings as defined above.
[802]
[803] In the above formula, R ^1-2-25a and R ^2-2-25a have the same meanings as R ¹ and R ² . Provided that at least one group of R ^1-2-25a and R ^2-2-25a represents an amino group or a group containing it, and the other symbols have the same meanings as defined above.
[804] This reaction can be carried out in the same manner as in the production of the compound represented by the general formula (I-1-9) described in [9].
[805] Among the compounds of the present invention represented by the formula (I-1), compounds in which at least one group of R ¹ or R ² is substituted with an oxycarbonyloxy group or a group containing the same, that is, The compound of the present invention to be displayed can also be prepared by reacting a compound in which at least one of R ¹ or R ² represents a hydroxyl group or a group containing it, that is, a compound represented by the following formula (I-2-26a) have.
[806]
[807] In the above formulas, R ^1-2-26 and R ^2-2-26 have the same meanings as R ¹ and R ² . With the proviso that at least one group of R ^1-2-26 and R ^2-2-26 represents an oxycarbonyloxy group substituted with a group containing it or the like and the other symbols have the same meanings as defined above.
[808]
[809] In the above formulas, R ^1-2-26a and R ^2-2-26a have the same meanings as R ¹ and R ² , provided that at least one of R ^1-2-26a and R ^2-2-26a is a hydroxyl group or And the other symbols have the same meanings as described above.
[810] This reaction can be carried out in the same manner as in the production of the compound represented by the general formula (I-1-9) described in [9].
[811] Among the compounds of the present invention represented by the formula (I-2), compounds in which at least one group of R ¹ or R ² represents a substituted (hydroxy) methyl group or a group containing the same, The compound of the present invention to be displayed can be produced by reacting a compound in which at least one of R ¹ or R ² represents a formyl group, that is, a compound represented by the following formula (I-2-27a) and the corresponding Grignard reagent or a corresponding derivative having lithium can do.
[812]
[813] In the above formulas, R ^1-2-27 and R ^2-2-27 have the same meanings as R ¹ and R ² . Provided that at least one of R ^1-2-27 and R ^2-2-27 represents a substituted (hydroxy) methyl group or a group containing it, and other symbols have the same meanings as defined above.
[814]
[815] In the above formulas, R ^1-2-27a and R ^2-2-27a have the same meanings as R ¹ and R ² . Provided that at least one of R ^1-2-27a and R ^2-2-27a represents a formyl group and the other symbols have the same meanings as defined above.
[816] This reaction can be carried out in the same manner as in the production of the compound represented by the general formula (I-1-11a) described in [11].
[817] Among the compounds of the present invention represented by the formula (I-2), compounds in which at least one group of R ¹ or R ² represents a substituted carbonyl group or a group containing the same, that is, The compound can also be produced by subjecting the compound represented by the above general formula (I-2-27) to an oxidation reaction.
[818]
[819] In the above formulas, R ^1-2-28 and R ^2-2-28 have the same meanings as R ¹ and R ² . Provided that at least one of R ^1-2-28 and R ^2-2-28 represents a substituted carbonyl group or a group containing it, and the other symbols have the same meanings as defined above.
[820] This oxidation reaction can be carried out in the same manner as in the production of the compound represented by the general formula (I-1-12) described in [12].
[821] Among the compounds of the present invention represented by the formula (I-2), compounds wherein at least one group of R ¹ or R ² represents an amino group or a group containing it, that is, a compound of the present invention represented by the formula (I- A compound represented by the following general formula (I-2-29a) wherein at least one of R ¹ and R ² represents a nitro group or a group containing a nitro group can be produced by a nitro group reduction reaction.
[822]
[823] In the above formulas, R ^1-2-29 and R ^2-2-29 have the same meanings as R ¹ and R ² . Provided that at least one group of R ^1-2-29 and R ^2-2-29 represents an amino group or a group containing it, and the other symbols have the same meanings as defined above.
[824]
[825] In the above formulas, R ^1-2-29a and R ^2-2-29a have the same meanings as R ¹ and R ² . With the proviso that at least one of R ^1-2-29a and R ^2-2-29a represents a nitro group or a group containing it, and other symbols have the same meanings as defined above.
[826] The reduction reaction of the nitro group can be carried out in the same manner as in the production of the compound represented by the general formula (I-1-13) described in [13].
[827] At least one group of R ¹ or R ² is a -COOH group or a group containing it, a hydroxyl group or a group containing it or an amino group or a group containing it, That is, the compound of the present invention represented by the following formula (I-2-30) is a compound in which a -COOH group, a hydroxyl group, an amino group, or a group containing them in the compound represented by the formula (I- -30a can also be produced by alkaline hydrolysis, deprotection under acidic conditions, deprotection reaction in silyl group, or deprotection reaction by hydrogenolysis.
[828]
[829] In the above formula R and R ^{1-2-30 2-2-30} has the same meanings as R ¹ and R ^2. However, R and R group is at least one of the ^{1-2-30 2-2-30} represents a group containing -COOH, hydroxy or amino group or combinations thereof, and the other symbols have the same meanings as defined above.
[830]
[831] In the above formulas, R ^1-2-30a and R ^2-2-30a have the same meanings as R ¹ and R ² . Provided that at least one group of R ^1-2-30a and R ^2-2-30a is protected with a -COOH group (for example, protected by a methyl group, an ethyl group, a t-butyl group and a benzyl group), a protected hydroxyl group ( (E.g., benzyloxycarbonyl, t-butoxycarbonyloxy, t-butyldimethylsilyl, acetyl or benzyl) or a protected amino group Fluoroacetyl group or the like) or a group containing them, and other symbols have the same meanings as defined above.
[832] The deprotection reaction by alkaline hydrolysis, deprotection reaction under acidic conditions, deprotection reaction with silyl group or hydrolysis is carried out in the same manner as in the method for producing the compound represented by formula (I-1-14) described in [14] can do.
[833] In the present invention, the deprotection reaction means a general deprotection reaction which can be easily understood by those skilled in the art, for example, alkaline hydrolysis, deprotection reaction under acidic conditions, deprotection reaction by hydrogenolysis, The desired compound of the present invention can be easily prepared.
[834] The protecting group of the carboxyl group may be a methyl group, an ethyl group, a t-butyl group, or a benzyl group, although those skilled in the art can easily understand it. Such as those described in TW Greene, Protective Groups in Organic Synthesis , Willie, New York, 1991, are used.
[835] Examples of the protecting group of the hydroxyl group include a methoxymethyl group, a tetrahydropyranyl group, a t-butyldimethylsilyl group, an acetyl group and a benzyl group, but there is no particular limitation as long as it is a group which can be easily and selectively removed. Such as those described in TW Greene, Protective Groups in Organic Synthesis , Willie, New York, 1991, are used.
[836] Examples of the protecting group of the amino group include a benzyloxycarbonyl group, a t-butoxycarbonyl group and a trifluoroacetyl group, but there is no particular limitation as long as it is a group which can be easily and selectively removed. For example, reference is made to TW Greene, Protective Groups in Organic Synthesis , Willie, New York, 1991.
[837] The compound represented by the formula (V) is known per se or can be easily prepared by the following reaction formula or a known method.
[838] X in the scheme represents a halogen atom.
[839]
[840] The compound represented by the formula (III), (IV) or (VI), (VII) or (VIII) used as a starting material is itself known or can be easily prepared by a known method.
[841] Next, a compound represented by the formula (I-1-1c) wherein A represents a benzene ring, R 'represents a carboxyl group, p represents 1 and R' is bonded at 4-position, that is, a compound represented by the formula (XI) Is an important intermediate in the preparation of the present invention. The method for preparing the above formula compound is shown in Scheme 5 above. Next, each step will be described in detail.
[842] The reaction for producing the compound represented by the formula (XIII) from the compound represented by the formula (XII) can be carried out, for example, in an inert organic solvent (acetonitrile, benzene, toluene, xylene, methylene chloride, chloroform, dimethoxyethane, tetrahydrofuran (Such as zinc iodide, zinc chloride, aluminum chloride, titanium chloride, lithium perchlorate, lithium tetrafluoride, lithium hexafluoride, etc.) and cyanide In the presence of a derivative (e.g., trimethylsilyl cyanide, diethyl aluminum cyanide, or diethyl cyanophosphonate) at 0 to 40 ° C.
[843] The reaction for producing the compound represented by the formula (XIV) from the compound represented by the formula (XIII) can be carried out, for example, in an inert organic solvent (benzene, toluene, ethyl acetate, dioxane, dimethoxyethane, diethyl ether, tetrahydrofuran , Mixed solvents thereof, etc.), oxidizing agents (such as 2,3-dichloro-5,6-dicyano-1,4-benzoquinone, chlororanyl (2,3,5,6-tetrachloro- Quinone) or the like) at room temperature to reflux temperature. Alternatively, among the organic solvents (ethylene glycol, oleic acid, diethylene glycol dimethyl ether, toluene, benzene, xylene and the like), hydrogen acceptors (nitrobenzene, maleic acid, cyclohexene, oleic acid, 1,5-cyclooctadiene, phenylacetylene , 2-butynic acid, etc.) and a metal catalyst (palladium-carbon, palladium hydroxide, palladium black, palladium, platinum dioxide, nickel, Raney nickel, ruthenium chloride, etc.) at 60 ° C to reflux conditions.
[844] The reaction for producing the compound represented by the general formula (XI) from the compound represented by the general formula (XIV) can be carried out in the presence of an alkali (sodium hydroxide , Potassium hydroxide, lithium hydroxide and the like) at 60 ° C under reflux conditions.
[845] In each reaction in the present specification, the reaction product may be purified by conventional purification means such as distillation under atmospheric pressure or reduced pressure, high performance liquid chromatography using silica gel or magnesium silicate, thin layer chromatography, column chromatography or washing, And the like. The purification may be performed for each reaction or may be performed after completion of several reactions.
[846] The optical isomer of the compound of the present invention represented by the general formula (I) can be obtained by a general optical resolution method (for example, fractionation by gas chromatography or high performance liquid chromatography, division by crystallization as a diastereomer salt or inclusion compound, Or the like), or may be produced by a general asymmetric synthesis method.
[847] Pharmacological activity
[848] The compound of the present invention represented by the formula (I) has an IL-6 and / or IL-12 production inhibitory activity by the following experiment.
[849] (1) Measurement of IL-6 production inhibitory activity and cytotoxicity
[850] [Experimental Method]
[851] Cell line A549 cells derived from 1.5 x 10 ⁴ human lung epithelium were suspended in 100 μl of a Dalboko modified Eagle medium (DMEM) supplemented with 0.5% fetal bovine serum (hereinafter abbreviated as FBS) and cultured in a 96-well microplate 20 [mu] l of various concentrations of the test compound dissolved in various solvents and a tumor necrosis factor-alpha [TNF-alpha (Genzyme Co., Cat. No. TNF-H)] dissolved in DMEM at a concentration of 12.5 ng / Was added. After culturing for 24 hours, 200 [mu] l of culture supernatant was recovered and the amount of produced IL-6 was analyzed by enzyme-linked immunosorbent assay (ELISA) method (R & D Systems, Cat. No. D6050], and the inhibitory activity of the test compound was calculated to obtain a 50% inhibitory concentration (IC ₅₀ ). To the cells from which the culture supernatant was removed, a solution of 3- (4,5-dimethyl-2-thiazolyl) -2,5-diphenyl-2H-tetrazolinium bromide in a concentration of 0.5 mg / , MTT (manufactured by Doujin Chemical Laboratories, Cat. No. 345-01821)] was added and cultured for 3 hours. After removal of the MTT solution, 100 쨉 l of methanol was added to dissolve the cells, and the cytotoxicity of the test compound was evaluated by measuring the absorbance at a wavelength of 570 nm with 690 nm as the target wavelength. As a result, the compounds of the present invention were found to inhibit IL-6 production with an IC ₅₀ of 20 μM or less. For example, the free compound of Example 20 (4) inhibited IL-6 production at an IC ₅₀ of 4.4 μM and did not show cytotoxicity at 10 μM.
[852] (2) Measurement of IL-12 production inhibitory activity and cytotoxicity
[853] Experimental Method
[854] 2.0 × 10 ⁵ peripheral blood mononuclear cells adjusted from the blood of healthy normal subjects were suspended in 170 μl of RPMI 1640 medium supplemented with 10% FBS by the Ficoll specific gravity centrifugation method (Pharmacia Biotech, Cat. No. 144040-02) (IFN-y (Serotec, Cat. No. PHP050)) at a concentration of 6000 units / ml dissolved in RPMI 1640 medium supplemented with 10% FBS was added to each well of 96 well micro And cultured in a plate for 24 hours. 10 μl of a lipopolysaccharide [LPS (Difco, Cat. No. 3120-25-0)] at a concentration of 6 μg / ml dissolved in RPMI 1640 supplemented with 10% FBS was added and cultured for 20 hours, followed by culturing 150 μl recovering the supernatant, and was determined by measuring the production of IL-12 amounts by ELISA (R & D Systems Inc., Cat. No. D1200) to calculate the inhibitory activity of the test compound of 50% production inhibition concentration (IC ₅₀₎ (J Exp. Med. , 183 , 147 (1996)). After removing 150 μl of the culture supernatant, 50 μl of a 1 mg / ml MTT solution dissolved in RPMI 1640 medium supplemented with 10% FBS was added and cultured for 3 hours. Then, 100 쨉 l of 2-propanol containing 0.04 N hydrochloric acid was added thereto to dissolve the cells, and the cytotoxicity of the test compound was evaluated by measuring the absorbance at a wavelength of 570 nm with 690 nm as the target wavelength. As a result, the compounds of the present invention were found to inhibit IL-12 production at an IC ₅₀ of 10 μM or less. For example, the hydrochloride compound of Example 20 (4) inhibited IL-12 production at an IC ₅₀ of 0.11 μM and did not show cytotoxicity at 1 μM.
[855] [toxicity]
[856] As described above, the toxicity of the compound of the present invention is extremely low and can be judged to be sufficiently safe for use as a medicine.
[857] [Application to medicine]
[858] The compounds of the present invention inhibit the production of IL-6 and / or IL-12 in animals including humans, especially humans, and can be used for various inflammatory diseases, sepsis, multiple myeloma, plasma cell leukemia, osteoporosis, Prophylactic and / or therapeutic treatment of nephritis, renal cell carcinoma, Kaposi sarcoma, chronic arthritic rheumatism, hypergammaglobulinemia, castman's disease, atrial myxoma, diabetes, autoimmune disease, hepatitis, multiple sclerosis, colitis, .
[859] In order to use the compound of the present invention represented by the general formula (I), the non-toxic salt thereof, the acid addition salt or the hydrate thereof for the aforementioned purposes, they are usually administered systemically or locally, orally or parenterally.
[860] The dose may vary depending on the age, body weight, symptom, therapeutic effect, administration method, treatment time, etc., but is usually administered orally several times per day in the range of 1 mg to 1,000 mg per one adult, or Parenteral administration (preferably intravenous administration) once a day to several times a day in the range of 0.1 mg to 100 mg per one adult, or intravenous administration in the range of 1 hour to 24 hours per day Continue administration.
[861] Of course, as described above, since the dosage varies depending on various conditions, an amount smaller than the above dose may be sufficient, and a case where it is necessary to exceed the range may be necessary.
[862] When the compound of the present invention is administered, it is used as a solid preparation for oral administration, a liquid for oral administration, an injection for parenteral administration, an external preparation, a suppository, and the like.
[863] Solid oral preparations for oral administration include tablets, pills, capsules, powders, granules and the like. Capsules include hard capsules and soft capsules.
[864] One or more active substances may be present as such or in the form of an excipient (lactose, mannitol, glucose, microcrystalline cellulose, starch, etc.), a binder (hydroxypropylcellulose, polyvinylpyrrolidone, (Magnesium stearate, etc.), a stabilizer, a solubilizing aid (glutamic acid, aspartic acid, etc.) and the like, and they are formulated according to a conventional method and used. Further, if necessary, it may be coated with a coating agent (such as white sugar, gelatin, hydroxypropylcellulose, hydroxypropylmethylcellulose phthalate), or may be coated with two or more layers. Also included are capsules of absorbable material such as gelatin.
[865] The intraoral solution for oral administration includes pharmaceutically acceptable materials, suspensions, emulsions, syrups, elixirs and the like. In such a liquid preparation, one or more active substances are dissolved, suspended or emulsified in a commonly used diluent (such as purified water, ethanol or a mixture thereof). The liquid agent may contain a wetting agent, a suspending agent, an emulsifying agent, a sweetening agent, a flavoring agent, a fragrance, a preservative, a buffering agent and the like.
[866] Injections for parenteral administration include solid injections which are dissolved or suspended in solutions, suspensions, emulsions and solvents for administration. Injections are used by dissolving, suspending or emulsifying one or more active substances in a solvent. As the solvent, for example, distilled water for injection, physiological saline, vegetable oil, alcohols such as propylene glycol, polyethylene glycol, ethanol and the like, and a combination thereof are used. In addition, the injectable preparation may contain a stabilizer, a dissolution aid (glutamic acid, aspartic acid, polysorbate 80 (registered trademark), etc.), a suspending agent, an emulsifying agent, an analgesic agent, a buffering agent and a preservative. These can be sterilized in the final process or prepared and prepared by aseptic manipulation. It is also possible to prepare a sterile solid product such as a freeze-dried product, and dissolve it in sterilized or sterile distilled water for main use or other solvent before use.
[867] Other preparations for parenteral administration include external solutions, ointments, coatings, inhalants, sprays, suppositories, and pessaries for vaginal administration, which contain one or more active substances and are prescribed by conventional methods.
[868] In addition to commonly used diluents, the spray may contain stabilizers such as sodium hydrogen sulfite and buffers which impart isotonicity, such as isotonic agents such as sodium chloride, sodium citrate or citric acid. Methods of preparing the spray agents are described in detail, for example, in U.S. Patent Nos. 2,868,691 and 3,095,355.
[869] Hereinafter, the present invention will be described in detail with reference to the following Reference Examples and Examples, but the present invention is not limited thereto.
[870] The solvent in the parentheses indicated in the place of separation by chromatography and the TLC indicates the dissolution solvent or developing solvent used, and the ratio represents the volume ratio.
[871] The solvent in the parentheses indicated in the section of NMR indicates the solvent used for the measurement.
[872] Example 1
[873] 3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[874]
[875] Triethylamine (1.55 ml) and thiophenol (798 mg) were added to a tetrahydrofuran (10 ml) solution of benzothiophene-1,1-dioxide (1 g). The reaction mixture was stirred at room temperature for 4 hours. Water was added to the reaction mixture and extracted with ethyl acetate. The extract was washed sequentially with water and saturated sodium chloride, dried over anhydrous sodium sulfate and concentrated. The residue was purified by silica gel column chromatography (hexane: ethyl acetate = 1: 1). Further, the obtained compound was recrystallized from ethanol to obtain the present compound (1.18 g) having the following physical properties.
[876] TLC: Rf 0.46 (hexane: AcOEt = 2: 1);
[877] _{NMR (CDCl 3): δ 7.85-7.18} (9H, m), 4.98 (1H, t, J = 7Hz), 3.80 (1H, dd, J = 14, 7Hz), 3.51 (1H, dd, J = 14, 7Hz).
[878] Examples 1 (1) to 1 (18)
[879] Instead of thiophenol, the thiol was used in the same manner as in Example 1 to obtain the compound of the present invention shown below.
[880] Example 1 (1)
[881] Synthesis of 3- (thiophen-2-yl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[882]
[883] TLC: Rf 0.53 (hexane: AcOEt = 1: 1);
[884] _{NMR (CDCl 3): δ 7.81-7.66} (m, 3H), 7.58-7.51 (m, 1H), 7.42 (dd, J = 5.4, 1.4Hz, 1H), 7.14 (dd, J = 3.6, 1.4Hz, J = 6.9 Hz, 1H), 3.80 (dd, J = 14.0, 7.2 Hz, 1H), 3.51 (dd, J = 14.0, 6.6 Hz, 1H).
[885] Example 1 (2)
[886] 3- (4-methylphenyl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[887]
[888] TLC: Rf 0.40 (hexane: AcOEt = 2: 1);
[889] _{NMR (CDCl 3): δ 7.85-7.57} (m, 4H), 7.42 (d, J = 8.0Hz, 2H), 7.21 (d, J = 8.0Hz, 2H), 4.80 (t- type, J = 6.5Hz , 1H), 3.85 (dd, J = 14.0, 7.5 Hz, 1H), 3.38 (dd, J = 14.0, 6.0 Hz, 1H).
[890] Example 1 (3)
[891] 3- (4-methoxyphenyl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[892]
[893] TLC: Rf 0.38 (hexane: AcOEt = 2: 1);
[894] _{NMR (CDCl 3): δ 7.82-7.45} (4H, m), 7.36 (2H, d, J = 7Hz), 6.85 (2H, d, J = 7Hz), 4.83 (1H, t, J = 7Hz), 3.83 (3H, s), 3.74 (1H, dd, J = 13,7Hz), 3.46 (1H, dd, J = 13,7Hz).
[895] Example 1 (4)
[896] 3- (4-Chlorophenyl) thio-2,3-dihydro-1,1-dioxo [b] thiophene
[897]
[898] TLC: Rf 0.37 (hexane: AcOEt = 2: 1);
[899] _{NMR (CDCl 3): δ 7.88-7.67} (m, 4H), 7.32 (d, J = 8.0Hz, 2H), 7.25 (d, J = 8.0Hz, 2H), 4.83 (t- type, J = 7.0Hz , 3.83 (dd, J = 14.5, 6.5 Hz, 1H), 3.52 (dd, J = 14.5, 7.8 Hz, 1H).
[900] Example 1 (5)
[901] Preparation of 3- (4-fluorophenyl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[902]
[903] TLC: Rf 0.36 (hexane: AcOEt = 2: 1);
[904] _{NMR (CDCl 3): δ 7.80-7.32} (m, 6H), 7.04 (t- type, J = 8.8Hz, 2H), 4.90 (t- type, J = 6.6Hz, 1H), 3.78 (dd, J = 13.6, 7.6 Hz, 1H), 3.50 (dd, J = 13.6, 6.4 Hz, 1H).
[905] Example 1 (6)
[906] 3- (4-hydroxyphenyl) thio-2,3-dihydro-1,1-dioxo [b] thiophene
[907]
[908] TLC: Rf 0.33 (hexane: AcOEt = 1: 1);
[909] _{NMR (CDCl 3): δ 3.45} (dd, J = 15, 7.5Hz, 1H), 3.75 (dd, J = 15, 7.5Hz, 1H), 4.80 (t, J = 7.5Hz, 1H), 5.60 (s (D, J = 7.5 Hz, 2H), 7.45-7.80 (m, 4H).
[910] Example 1 (7)
[911] 3- (3-hydroxyphenyl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[912]
[913] TLC: Rf 0.36 (hexane: AcOEt = 1: 1);
[914] _{NMR (CDCl 3): δ 3.50} (dd, J = 15, 7.5Hz, 1H), 3.85 (dd, J = 15, 7.5Hz, 1H), 5.00 (t, J = 7.5Hz, 1H), 5.65 (s , 1H), 6.75-7.00 (m, 3H), 7.10-7.30 (m, 1H), 7.50-7.80 (m, 4H).
[915] Example 1 (8)
[916] Preparation of 3- (2-hydroxyphenyl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[917]
[918] TLC: Rf 0.33 (hexane: AcOEt = 1: 1);
[919] _{NMR (CDCl 3): δ 3.45} (dd, J = 12.5, 5.0Hz, 1H), 3.70 (dd, J = 12.5, 7.5Hz, 1H), 4.80 (dd, J = 7.5, 5.0Hz, 1H), 6.65 (s, 1H), 6.90 (t, J = 7.5 Hz, 1H), 7.00 (d, J = 7.5 Hz, 1H), 7.30-7.80 (m, 6H).
[920] Example 1 (9)
[921] 3- (Pyridin-4-yl) thio-2,3-dihydro-1, 1-dioxide benzo [b] thiophene
[922]
[923] TLC: Rf 0.45 (ethyl acetate);
[924] _{NMR (CDCl 3): δ 3.58} (dd, J = 13, 6Hz, 1H), 4.00 (dd, J = 13, 6Hz, 1H), 5.22 (t, J = 6Hz, 1H), 7.20 (m, 2H) , &Lt; / RTI &gt; 7.69 (m, 4H), 8.51 (m, 2H).
[925] Example 1 (10)
[926] 3- (Pyrimidin-2-yl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[927]
[928] TLC: Rf 0.55 (hexane: AcOEt = 1: 2);
[929] _{NMR (CDCl 3): δ 3.71} (dd, J = 14, 7Hz, 1H), 4.24 (dd, J = 14, 7Hz, 1H), 5.70 (t, J = 7Hz, 1H), 7.10 (t, J = 5 Hz, 1 H), 7.52-7.85 (m, 4H), 8.58 (d, J = 5 Hz, 2H).
[930] Example 1 (11)
[931] Preparation of 3- (thiazol-2-yl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[932]
[933] TLC: Rf 0.52 (hexane: AcOEt = 1: 1);
[934] NMR (CDCl ₃ ): 隆 3.55 (dd, J = 13, 4 Hz, 1H), 3.81 (dd, J = 13,7 Hz, 1H), 5.60 (dd, J = 7, 4 Hz, 1H), 7.57-7.80 m, 6H).
[935] Example 1 (12)
[936] 3- (3-methylfuran-2-yl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[937]
[938] TLC: Rf 0.45 (hexane: AcOEt = 4: 1);
[939] _{NMR (CDCl 3): δ 2.27} (s, 3H), 3.39 (dd, J = 14.0Hz, 6.0Hz, 1H), 3.75 (dd, J = 14.0Hz, 6.0Hz, 1H), 4.69 (t, J = 6.0 Hz, 1H), 6.07 (d, J = 2.0 Hz, 1H), 7.25 (d, J = 2.0 Hz, 1H), 7.48-7.77 (m, 4H).
[940] Example 1 (13)
[941] Preparation of 3- (3-methoxyphenyl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[942]
[943] TLC: Rf 0.44 (hexane: AcOEt = 1: 1);
[944] _{NMR (CDCl 3): δ 3.50} (dd, J = 12.5, 7.5Hz, 1H), 3.75 (s, 3H), 3.80 (dd, J = 12.5, 7.5Hz, 1H), 5.00 (t, J = 7.5Hz , 1H), 6.85-7.05 (m, 3H), 7.20-7.30 (m, 1H), 7.50-7.80 (m, 4H).
[945] Example 1 (14)
[946] Preparation of 3- (2-methoxycarbonylphenyl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[947]
[948] TLC: Rf 0.40 (hexane: AcOEt = 1: 1);
[949] _{NMR (CDCl 3): δ 3.60} (dd, J = 15, 7.5Hz, 1H), 3.90 (s, 3H), 3.95 (dd, J = 15, 7.5Hz, 1H), 5.25 (t, J = 7.5Hz , &Lt; / RTI &gt; 1H), 7.30-7.80 (m, 7H), 7.95-8.05 (m, 1H).
[950] Example 1 (15)
[951] 3-cyclohexylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[952]
[953] TLC: Rf 0.32 (hexane: AcOEt = 3: 1);
[954] _{NMR (CDCl 3): δ 1.26-2.10} (m, 10H), 2.80-2.93 (m, 1H), 3.52 (dd, J = 13.4, 7.4Hz, 1H), 3.92 (dd, J = 13.4, 7.4Hz, 1H), 4.68 (t, J = 7.4 Hz, 1H), 7.47-7.54 (m, 1H), 7.59-7.67 (m, 1H), 7.70-7.75 (m, 2H).
[955] Example 1 (16)
[956] 3- (naphthalen-1-yl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[957]
[958] TLC: Rf 0.37 (hexane: AcOEt = 2: 1);
[959] NMR (CDCl ₃ ): 3.51 (dd, J = 13.6, 5.8 Hz, 1H), 3.64 (dd, J = 13.6 Hz, 7.3 Hz, 1H) 7.40-7.79 (m, 8H), 7.90-7.94 (m, 2H), 8.52-8.56 (m, 1H).
[960] Example 1 (17)
[961] 3- (2-methoxyphenyl) thio-2,3-dihydro-1, 1-dioxide benzo [b] thiophene
[962]
[963] TLC: Rf 0.49 (hexane: AcOEt = 1: 1);
[964] _{NMR (CDCl 3): δ 3.55} (dd, J = 12.5, 7.5Hz, 1H), 3.75 (dd, J = 12.5, 7.5Hz, 1H), 3.90 (s, 3H), 5.10 (t, J = 7.5Hz , &Lt; / RTI &gt; 1H), 6.90-7.00 (m, 2H), 7.30-7.80 (m, 6H).
[965] Example 1 (18)
[966] 2-yl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[967]
[968] TLC: Rf 0.50 (hexane: AcOEt = 1: 2);
[969] NMR (CDCl ₃ ): 隆 3.54 (dd, J = 14, 3 Hz, 1H), 3.65 (s, 3H), 4.04 (dd, J = ), 6.65 (d, J = 2.7 Hz, 1H), 6.95 (dd, J = 9, 3 Hz, 1H), 7.56 (m, 1H), 7.67 (m, 2H), 7.85
[970] Example 2
[971] 3-phenylsulfinyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[972]
[973] Water (10 ml) was added to potassium peroxymonosulfate ("Oxon" (trade name) manufactured by Aldrich Co., hereinafter abbreviated as Oxone) 2.14 g). To the methanol (50 ml) solution of the compound (0.961 g) prepared in Example 1 at 0 占 폚 was added the oxone aqueous solution (5.5 ml) prepared above. The reaction mixture was stirred at 0 &lt; 0 &gt; C for 30 min. Water was added to the reaction mixture and extracted with ethyl acetate. The extract was washed with a saturated aqueous sodium chloride solution (x2), dried over anhydrous sodium sulfate and concentrated. The residue was recrystallized from ethanol to obtain the compound (361 mg) of the present invention having the following physical properties.
[974] TLC: Rf 0.13 (hexane: AcOEt = 1: 1);
[975] _{NMR (CDCl 3): δ 7.85-7.45} (9H, m), 4.57 (1H, t, J = 7Hz), 3.98 (1H, dd, J = 14, 7Hz), 3.19 (1H, dd, J = 14, 7Hz).
[976] Example 2 (1) to (2)
[977] The compound of the present invention shown below was obtained by following the procedure of Example 2 while using the compound prepared in Example 1 (1) and Example 1 (14) in place of the compound prepared in Example 1.
[978] Example 2 (1)
[979] 3- (thiophen-2-yl) sulfinyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[980]
[981] TLC: Rf 0.01 (hexane: AcOEt = 1: 1);
[982] _{NMR (CDCl 3): δ 7.95-7.50} (4.5 H m), 7.50-7.25 (1.5H, m), 7.25-7.10 (1H, m), 4.99 (0.5H, dd, J = 8.4, 4Hz), 4.81 (0.5H, dd, J = 8.4,4Hz), 4.02 (0.5H, dd, J = 14.2,4.4Hz), 3.72-3.40 (1.5H, m).
[983] Example 2 (2)
[984] Preparation of 3- (2-methoxycarbonylphenyl) sulfinyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[985]
[986] TLC: Rf 0.33 (hexane: AcOEt = 1: 1);
[987] _{NMR (CDCl 3): δ 2.90} (dd, J = 12.5, 7.5Hz, 1H), 4.00 (s, 3H), 4.00 (dd, J = 12.5, 7.5Hz, 1H), 5.05 (t, J = 7.5Hz , 1H), 7.55-7.90 (m, 5H), 8.10-8.25 (m, 3H).
[988] Example 3
[989] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene.
[990]
[991] To oxone (2.14 g) was added water (10 mL). To the methanol (50 ml) solution of the compound (0.961 g) prepared in Example 1 was added the oxone aqueous solution prepared above at room temperature. The reaction mixture was stirred at room temperature for 2 hours. Water was added to the reaction mixture and extracted with ethyl acetate. The extract was washed sequentially with water (x2) and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and concentrated. The residue was recrystallized from ethanol to obtain the compound (1.54 g) of the present invention having the following properties.
[992] TLC: Rf 0.45 (hexane: AcOEt = 1: 1);
[993] _{NMR (CDCl 3): δ 3.65-3.85} (m, 2H), 5.10 (dd, J = 10, 5.0Hz, 1H), 7.40-7.80 (m, 8H), 8.05 (d, J = 10Hz, 1H).
[994] Example 3 (1) to 3 (17)
[995] The compound prepared in Example 1 (1) to Example 17 (17) was used instead of the compound prepared in Example 1, and the procedure of Example 3 was repeated, except that 3-chlorobenzoic acid was used instead of oxone as an oxidizing agent To give the following compounds of the present invention.
[996] Example 3 (1)
[997] Synthesis of 3- (thiophen-2-yl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[998]
[999] TLC: Rf 0.18 (hexane: AcOEt = 2: 1);
[1000] NMR (CDCl ₃ ): 8.08 (d, J = 5.0 Hz, 1H), 7.82-7.66 (m, 5H), 7.20 (dd, J = 5.0, 3.8 Hz, 1H) 3.1 Hz, 1H), 4.07 (dd, J = 15.4, 9.4 Hz, 1H), 3.83 (dd, J = 15.4, 3.1 Hz, 1H).
[1001] Example 3 (2)
[1002] Preparation of 3- (4-methylphenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1003]
[1004] TLC: Rf 0.11 (hexane: AcOEt = 2: 1);
[1005] _{NMR (CDCl 3): δ 8.04} (1H, d, J = 8Hz), 7.82-7.58 (3H, m), 7.53 (2H, d, J = 9Hz), 7.28 (2H, d, J = 9Hz), 5.08 (1H, dd, J = 11, 8 Hz), 3.86-3.55 (2H, m), 2.42 (3H, s).
[1006] Example 3 (3)
[1007] Preparation of 3- (4-methoxyphenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1008]
[1009] TLC: Rf 0.23 (hexane: AcOEt = 1: 1);
[1010] _{NMR (CDCl 3): δ 8.04} (1H, d, J = 8Hz), 7.88-7.60 (3H, m), 7.54 (2H, d, J = 7Hz), 6.91 (2H, d, J = 7Hz), 5.06 (1H, t, J = 7 Hz), 3.85 (3H, s), 3.80-3.60 (2H, m).
[1011] Example 3 (4)
[1012] Preparation of 3- (4-chlorophenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1013]
[1014] TLC: Rf 0.26 (hexane: AcOEt = 2: 1);
[1015] _{NMR (CDCl 3): δ 8.02} (1H, d, J = 8Hz), 7.85-7.58 (3H, m), 7.58-7.32 (4H, m), 5.09 (1H, t, J = 7Hz), 3.90-3.65 (2H, m).
[1016] Example 3 (5)
[1017] 3- (4-fluorophenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1018]
[1019] TLC: Rf 0.41 (hexane: AcOEt = 1: 1);
[1020] _{NMR (CDCl 3): δ 8.03} (1H, d, J = 8Hz), 7.90-7.45 (5H, m), 7.20-7.00 (2H, m), 5.08 (1H, t, J = 7Hz), 3.80-3.75 (2H, m).
[1021] Example 3 (6)
[1022] Preparation of 3- (4-hydroxyphenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1023]
[1024] TLC: Rf 0.27 (hexane: AcOEt = 1: 1);
[1025] _{NMR (CD 3 OD + CDCl 3} ): δ 7.97 (1H, d, J = 7Hz), 7.85-7.55 (3H, m), 7.46 (2H, d, J = 9Hz), 6.84 (2H, d, J = 9Hz), 5.09 (1H, t, J = 7 Hz), 3.90-3.60 (2H, m).
[1026] Example 3 (7)
[1027] Preparation of 3- (3-hydroxyphenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1028]
[1029] TLC: Rf 0.22 (hexane: AcOEt = 1: 1);
[1030] NMR (CDCl ₃ + DMSO-d ₆ ): δ 9.83 (1H, brs), 7.90-7.78 (1H, m), 7.78-7.50 (3H, m), 7.42-7.08 1H, &lt; / RTI &gt; m), 3.90-3.58 (2H, m).
[1031] Example 3 (8)
[1032] Preparation of 3- (2-hydroxyphenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1033]
[1034] TLC: Rf 0.15 (hexane: AcOEt = 1: 1);
[1035] _{NMR (CDCl 3 + DMSO-d} 6): δ 7.90-7.42 (6H, m), 7.13 (1H, d, J = 8Hz), 6.98 (1H, t, J = 7Hz), 5.71 (1H, dd, J = 9, 5 Hz), 3.86 (1H, dd, J = 14, 5 Hz), 3.65 (1H, dd, J = 14, 9 Hz).
[1036] Example 3 (9)
[1037] 3- (Pyridin-4-yl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1038]
[1039] TLC: Rf 0.25 (hexane: AcOEt = 1: 2);
[1040] _{NMR (DMSO-d 6):} δ 3.87 (dd, J = 15, 3Hz, 1H), 4.03 (dd, J = 15, 9Hz, 1H), 5.94 (dd, J = 9, 3Hz, 1H), 7.70 ( dd, J = 4, 2 Hz, 2H), 7.81 (m, 4H), 8.88 (dd, J = 4, 2 Hz, 2H).
[1041] Example 3 (10)
[1042] 3- (Pyrimidin-2-yl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1043]
[1044] TLC: Rf 0.15 (dichloromethane);
[1045] _{NMR (DMSO-d 6):} δ 4.00 (dd, J = 16, 4Hz, 1H), 4.12 (dd, J = 16, 9Hz, 1H), 6.17 (dd, J = 9, 4Hz, 1H), 7.78 ( m, 3H), 7.90 (m, 2H), 9.09 (dd, J = 5, 1 Hz, 2H).
[1046] Example 3 (11)
[1047] Preparation of 3- (thiazol-2-yl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1048]
[1049] TLC: Rf 0.40 (hexane: AcOEt = 1: 1);
[1050] _{NMR (CDCl 3): δ 3.87} (dd, J = 15, 9Hz, 1H), 4.20 (dd, J = 15, 5Hz, 1H), 5.39 (dd, J = 9, 5Hz, 1H), 7.61-7.81 ( m, 4H), 7.99-8.08 (m, 2H).
[1051] Example 3 (12)
[1052] 3- (3-methylfuran-2-yl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1053]
[1054] TLC: Rf 0.50 (hexane: AcOEt = 3: 2);
[1055] _{NMR (CDCl 3): δ 2.39} (s, 3H), 3.78 (dd, J = 15, 4Hz, 1H), 3.88 (dd, J = 15, 8Hz, 1H), 5.00 (dd, J = 8, 4Hz, 1H), 5.98 (d, J = 2 Hz, 1H), 7.18 (d, J = 2 Hz, 1H), 7.60-7.80 (m, 3H), 8.02
[1056] Example 3 (13)
[1057] Preparation of 3- (3-methoxyphenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1058]
[1059] TLC: Rf 0.33 (hexane: AcOEt = 1: 1);
[1060] _{NMR (CDCl 3): δ 3.65-3.90} (m, 2H), 3.75 (s, 3H), 5.10 (dd, J = 10, 5.0Hz, 1H), 7.10-7.50 (m, 4H), 7.60-7.80 ( m, 3H), 8.00 (d, J = 7.5 Hz, 1H).
[1061] Example 3 (14)
[1062] Preparation of 3- (2-methoxycarbonylphenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1063]
[1064] TLC: Rf 0.59 (methylene chloride: ethyl acetate = 9: 1);
[1065] _{NMR (CDCl 3): δ 8.01-7.97} (m, 1H), 7.84-7.63 (m, 7H), 6.06 (dd, J = 9.0, 4.5Hz, 1H), 4.04 (s, 3H), 3.92 (dd, J = 14.0, 4.5 Hz, 1H), 3.63 (dd, J = 14.0, 9.0 Hz, 1H).
[1066] Example 3 (15)
[1067] 3-cyclohexylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1068]
[1069] TLC: Rf 0.37 (hexane: AcOEt = 1: 1);
[1070] _{NMR (CDCl 3): δ 1.13-1.68} (m, 8H), 1.90-1.96 (m, 1H), 2.15-2.19 (m, 1H), 3.07-3.23 (m, 1H), 3.87 (dd, J = 14.5 J = 8.2, 5.2 Hz, 1H), 7.63-7.83 (m, 3H), 7.96-8.00 (m, 1H).
[1071] Example 3 (16)
[1072] Synthesis of 3- (naphthalen-1-yl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1073]
[1074] TLC: Rf 0.40 (hexane: AcOEt = 1: 1);
[1075] _{NMR (CDCl 3): δ 3.38} (dd, J = 14.4, 8.8Hz, 1H), 3.77 (dd, J = 14.4, 5.0Hz, 1H), 5.31 (dd, J = 8.8, 5.0Hz, 1H), 7.60 -7.81 (m, 7H), 8.00-8.05 (m, 1H), 8.22-8.28 (m, 2H), 8.72-8.77 (m, 1H).
[1076] Example 3 (17)
[1077] Preparation of 3- (2-methoxyphenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1078]
[1079] TLC: Rf 0.20 (hexane: AcOEt = 1: 1);
[1080] _{NMR (CDCl 3 + DMSO-d} 6): δ 3.65 (dd, J = 15, 10Hz, 1H), 3.80 (dd, J = 15, 5.0Hz, 1H), 4.00 (s, 3H), 5.55 (dd, J = 10, 5.0 Hz, 1H), 7.05-7.20 (m, 2H), 7.60-7.95 (m, 6H).
[1081] Example 4
[1082] Phenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1083]
[1084] N-Chloroethylpiperidine (193 mg) and cesium carbonate (1.0 g) were added to a dimethylformamide (5 ml) solution of the compound (283 mg) prepared in Example 3 (6). The reaction mixture was stirred overnight at room temperature. Water was added to the reaction mixture and extracted with ethyl acetate. The extract was washed with water (x3), saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and concentrated. The residue was purified by silica gel column chromatography (hexane: ethyl acetate = 1: 1) to obtain the compound (186 mg) of the present invention having the following physical data.
[1085] TLC: Rf 0.54 (ethyl acetate: methanol: 28% ammonia water = 100: 10: 1);
[1086] _{NMR (CDCl 3): δ 8.03} (1H, d, J = 7Hz), 7.85-7.55 (3H, m), 7.53 (2H, d, J = 9Hz), 6.92 (2H, d, J = 9Hz), 5.05 (2H, t, J = 6 Hz), 2.49 (4H, brt, J = 6 Hz) ), 1.68-1.45 (6 H, m).
[1087] Examples 4 (1) to 4 (4)
[1088] The compound prepared in Examples 3 (6) to 3 (8) and the corresponding halide were used in the same manner as in Example 4 to obtain the following compounds of the present invention.
[1089] Example 4 (1)
[1090] Phenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1091]
[1092] TLC: Rf 0.35 (ethyl acetate: methanol: 28% ammonia water = 100: 10: 1);
[1093] _{NMR (CDCl 3): δ 8.03} (1H, d, J = 7Hz), 7.90-7.40 (5H, m), 6.93 (2H, d, J = 7Hz), 5.18-4.95 (1H, m), 4.14 (2H , t, J = 6 Hz), 3.90-3.60 (2H, m), 2.91 (2H, t, J = 6 Hz), 2.75-2.40 (4H, m), 1.84-1.74 (4H, m).
[1094] Example 4 (2)
[1095] Phenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1096]
[1097] TLC: Rf 0.44 (ethyl acetate: methanol: 28% ammonia water = 100: 10: 1);
[1098] _{NMR (CDCl 3): δ 8.05} (1H, d, J = 7Hz), 7.85-7.40 (5H, m), 6.91 (2H, d, J = 7Hz), 5.06 (1H, t, J = 7Hz), 4.13 (2H, t, J = 6Hz), 3.95-3.50 (6H, m), 2.80 (2H, t, J = 6Hz), 2.70-2.40 (4H, m).
[1099] Example 4 (3)
[1100] Preparation of 3- (3-benzyloxyphenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1101]
[1102] TLC: Rf 0.55 (hexane: AcOEt = 1: 1);
[1103] _{NMR (CDCl 3): δ 8.02} (1H, d, J = 7Hz), 7.85-7.52 (3H, m), 7.52-7.10 (9H, m), 5.15-4.85 (3H, m), 3.80-3.45 (2H , m).
[1104] Example 4 (4)
[1105] 3- (2-benzyloxyphenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1106]
[1107] TLC: Rf 0.37 (hexane: AcOEt = 1: 1);
[1108] _{NMR (CDCl 3): δ 7.93} (1H, dd, J = 8, 2Hz), 7.85-7.30 (10H, m), 7.25-7.08 (2H, m), 5.52 (1H, dd, J = 9, 5Hz) , 5.28 (2H, s), 3.79 (1H, dd, J = 14,5Hz), 3.48 (1H, dd, J = 14,9Hz).
[1109] Example 5
[1110] Phenyl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1111]
[1112] The procedure of Example 4 was repeated except that the compound prepared in Example 1 (6) and the corresponding halide were used instead of the compound prepared in Example 3 (6) and N-chloroethylpiperidine was used A compound of the present invention having the following physical properties was obtained.
[1113] TLC: Rf 0.58 (ethyl acetate);
[1114] _{NMR (CDCl 3): δ 8.65-8.55} (1H, m), 7.80-7.20 (9H, m), 7.00-6.90 (2H, m), 5.20 (2H, s), 4.85 (1H, t, J = 7.5 Hz), 3.75 (1H, dd, J = 12.5, 7.5 Hz), 3.45 (1H, dd, J = 12.5, 7.5 Hz).
[1115] Examples 5 (1) to 5 (9)
[1116] The compound of the present invention shown below was obtained in the same manner as in the method of Example 5 by using the compound prepared in Example 1 (6) to (8) and the corresponding halide.
[1117] Example 5 (1)
[1118] 3- (4- (pyridin-3-ylmethyloxy) phenyl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1119]
[1120] TLC: Rf 0.42 (ethyl acetate);
[1121] _{NMR (CDCl 3): δ 8.70-8.60} (2H, m), 7.80-7.30 (8H, m), 7.00-6.90 (2H, m), 5.05 (2H, s), 4.85 (1H, t, J = 5Hz ), 3.75 (1H, dd, J = 15,5Hz), 3.45 (1H, dd, J = 15,5Hz).
[1122] Example 5 (2)
[1123] Phenyl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1124]
[1125] TLC: Rf 0.33 (ethyl acetate);
[1126] _{NMR (CDCl 3): δ 8.65-8.60} (2H, m), 7.80-7.30 (8H, m), 7.00-6.90 (2H, m), 5.10 (2H, s), 4.85 (1H, t, J = 5Hz ), 3.75 (1H, dd, J = 15,5Hz), 3.45 (1H, dd, J = 15,5Hz).
[1127] Example 5 (3)
[1128] 3- (4- (3-Hydroxypropyloxy) phenyl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1129]
[1130] TLC: Rf 0.14 (hexane: AcOEt = 1: 1);
[1131] _{NMR (CD 3 OD): δ} 1.90-2.10 (m, 2H), 3.30-3.50 (m, 1H), 3.50-4.00 (m, 3H), 4.00-4.20 (m, 2H), 4.90-5.10 (m, 1H), 6.80-7.00 (m, 2H), 7.30-7.50 (m, 2H), 7.50-7.80 (m, 4H).
[1132] Example 5 (4)
[1133] 3- (3- (pyridin-3-ylmethyloxy) phenyl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1134]
[1135] TLC: Rf 0.44 (ethyl acetate);
[1136] _{NMR (CDCl 3): δ 3.50} (dd, J = 12.5, 7.5Hz, 1H), 3.80 (dd, J = 12.5, 7.5Hz, 1H), 4.95-5.10 (m, 1H), 5.00 (s, 2H) , 6.90-7.10 (m, 3H), 7.20-7.40 (m, 2H), 7.50-7.80 (m, 5H), 8.50-8.70 (m, 2H).
[1137] Example 5 (5)
[1138] 3- (3- (3-hydroxypropyloxy) phenyl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1139]
[1140] TLC: Rf 0.17 (hexane: AcOEt = 1: 1);
[1141] _{NMR (CDCl 3): δ 1.95-2.05} (m, 2H), 3.50 (dd, J = 12.5, 7.5Hz, 1H), 3.80 (dd, J = 12.5, 7.5Hz, 1H), 3.85 (t, J = 7.50 Hz, 2H), 4.05 (t, J = 7.5 Hz, 2H), 5.00 (t, J = 7.5 Hz, 1H), 6.80-7.05 (m, 3H), 7.20-7.30 7.80 (m, 4H).
[1142] Example 5 (6)
[1143] 3- (2- (pyridin-3-ylmethyloxy) phenyl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1144]
[1145] TLC: Rf 0.16 (hexane: AcOEt = 1: 1);
[1146] _{NMR (CD 3 OD): δ} 3.50 (dd, J = 15, 5.0Hz, 1H), 3.85 (dd, J = 15, 7.5Hz, 1H), 5.20 (dd, J = 7.5, 5.0Hz, 1H), J = 7.5 Hz, 1H), 7.20 (d, J = 7.5 Hz, 1H), 7.35-7.70 (m, 7H), 8.00 ), 8.50 (dd, J = 5.0, 2.5 Hz, 1H), 8.70 (d, J = 2.5 Hz, 1H).
[1147] Example 5 (7)
[1148] 3- (2- (3-hydroxypropyloxy) phenyl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1149]
[1150] TLC: Rf 0.30 (hexane: AcOEt = 1: 2);
[1151] _{NMR (CDCl 3): δ 2.05-2.10} (m, 2H), 2.30-2.60 (m, 1H), 3.50 (dd, J = 15, 5.0Hz, 1H), 3.70 (dd, J = 15, 7.5Hz, J = 7.5, 5.0 Hz, 1H), 6.90-7.00 (m, 2H), 7.30-7.80 (m, 2H) (m, 6 H).
[1152] Example 5 (8)
[1153] Phenyl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1154]
[1155] TLC: Rf 0.30 (toluene: ethyl acetate = 4: 1);
[1156] _{NMR (CDCl 3): δ 7.80-7.10} (6H, m), 6.80 (2H, d, J = 10Hz), 5.10-4.70 (2H, m), 4.00 (2H, t, J = 5Hz), 3.75 (1H , dd, J = 15, 7.5 Hz), 3.60-3.40 (3H, m), 1.45 (9H, s).
[1157] Example 5 (9)
[1158] Phenyl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1159]
[1160] TLC: Rf 0.40 (hexane: AcOEt = 1: 1);
[1161] _{NMR (CDCl 3): δ 7.80-7.50} (4H, m), 7.40-7.20 (1H, m), 7.05-6.70 (3H, m), 5.05-4.90 (2H, m), 3.95 (2H, t, J = 5 Hz), 3.80 (1H, dd, J = 15, 5 Hz), 3.60-3.40 (3H, m), 1.45 (9H, s).
[1162] Example 6
[1163] 2-ylmethyloxy) phenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1164]
[1165] Using the compound prepared in Example 5 instead of the compound prepared in Example 1, the same procedure as in Example 3 was conducted and the compound of the present invention having the following physical data was obtained by converting the compound into the hydrochloride salt by a known method &Lt; / RTI &gt;
[1166] Free body:
[1167] TLC: Rf 0.44 (ethyl acetate);
[1168] _{NMR (DMSO-d 6):} δ 8.60-8.55 (1H, m), 7.90-7.60 (7H, m), 7.50 (1H, d, J = 7.5Hz), 7.40-7.30 (1H, m), 7.20 ( Dd, J = 7.5 Hz), 5.70 (1H, dd, J = 10, 2.5 Hz), 5.30 (2H, s), 4.00 J = 15, 2.5 Hz).
[1169] Hydrochloride:
[1170] TLC: Rf 0.49 (ethyl acetate: triethylamine = 19: 1);
[1171] _{NMR (CD 3 OD): δ} 3.80 (dd, J = 15, 2.5Hz, 1H), 3.95 (dd, J = 15, 10Hz, 1H), 5.50 (dd, J = 10, 2.5Hz, 1H), 5.60 (s, 2H), 7.20 (d, J = 7.5 Hz, 2H), 7.55-8.00 (m, 4H), 7.70 (d, J = 7.5Hz, 2H), 8.05-8.25 8.95 (m, 2H).
[1172] Examples 6 (1) to 6 (9)
[1173] Using the compound prepared in Example 5 (1) to 5 (9) instead of the compound prepared in Example 5, the title compound was obtained in the same manner as in Example 6, except that 3-chlorobenzoic acid was used instead of oxone as an oxidizing agent And, if necessary, converted into the corresponding salt by a known method to obtain a compound of the present invention as shown below.
[1174] Example 6 (1)
[1175] 3- (4- (pyridin-3-ylmethyloxy) phenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1176]
[1177] Free body:
[1178] TLC: Rf 0.27 (ethyl acetate);
[1179] _{NMR (CDCl 3): δ 8.70-8.55} (2H, m), 8.10-8.00 (1H, m), 7.80-7.50 (6H, m), 7.40-7.30 (1H, m), 7.10-6.90 (2H, m ), 5.15 (2H, s), 5.20-5.00 (1H, m), 3.90-3.70 (2H, m).
[1180] Hydrochloride:
[1181] TLC: Rf 0.38 (ethyl acetate: triethylamine = 19: 1);
[1182] (CD ₃ OD): 隆 3.80 (dd, J = 15, 2.5 Hz, 1H), 3.95 (dd, J = 15,10 Hz, 1H), 5.45 (s, 2H), 5.45-5.55 , 7.20 (d, J = 10 Hz, 2H), 7.60-8.00 (m, 4H), 7.60 (d, J = 10 Hz, 2H), 8.10-8.20 (m, 1H), 8.70-9.00 (m, 3H).
[1183] Example 6 (2)
[1184] Phenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1185]
[1186] Free body:
[1187] TLC: Rf 0.22 (ethyl acetate);
[1188] _{NMR (DMSO-d 6):} δ 8.60 (2H, d, J = 5Hz), 7.90-7.65 (6H, m), 7.45 (2H, d, J = 5Hz), 7.20 (2H, d, J = 7.5Hz Dd, J = 7.5, 2.5 Hz), 5.30 (2H, s), 4.00 (1H, dd, J = 15, 7.5 Hz), 3.80 .
[1189] Hydrochloride:
[1190] TLC: Rf 0.35 (ethyl acetate: triethylamine = 19: 1);
[1191] _{NMR (DMSO-d 6):} δ 3.80 (dd, J = 15, 2.5Hz, 1H), 4.00 (dd, J = 15, 10Hz, 1H), 5.55 (s, 2H), 5.75 (dd, J = 10 , 7.95 (d, J = 7.5 Hz, 2H), 7.25 (d, J = 10 Hz, 2H), 7.65-7.90 8.90 (d, J = 7.5 Hz, 2H).
[1192] Example 6 (3)
[1193] 3- (4- (3-hydroxypropyloxy) phenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1194]
[1195] TLC: Rf 0.33 (ethyl acetate);
[1196] _{NMR (CDCl 3): δ 2.05} (5 quint, J = 5.0Hz, 2H), 3.70-3.90 (m, 2H), 3.85 (t, J = 5.0Hz, 2H), 4.15 (t, J = 5.0Hz, (D, J = 10 Hz, 2H), 5.05 (t, J = 7.5 Hz, 1H), 6.90 J = 7.5 Hz, 1H).
[1197] Example 6 (4)
[1198] 3- (3- (pyridin-3-ylmethyloxy) phenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene hydrochloride
[1199]
[1200] TLC: Rf 0.60 (ethyl acetate: methanol: triethylamine = 16: 2: 1);
[1201] _{NMR (CD 3 OD): δ} 3.85 (dd, J = 15, 5.0Hz, 1H), 3.95 (dd, J = 15, 10Hz, 1H), 5.35 (d, J = 12.5Hz, 1H), 5.45 (d J = 10.5 Hz, 1H), 5.55 (dd, J = 10, 5.0 Hz, 1H), 7.20-7.85 1H), 8.75 (d, J = 7.5 Hz, 1H), 8.85 (d, J = 5.0 Hz, 1H), 9.00 (s, 1H).
[1202] Example 6 (5)
[1203] 3- (3- (3-hydroxypropyloxy) phenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1204]
[1205] TLC: Rf 0.33 (ethyl acetate);
[1206] _{NMR (CDCl 3): δ 1.90-2.20} (m, 2H), 3.65-3.90 (m, 4H), 3.95-4.20 (m, 2H), 5.10 (dd, J = 10, 5.0Hz, 1H), 7.10- 7.30 (m, 3H), 7.30-7.45 (m, 1H), 7.60-7.80 (m, 3H), 8.00 (d, J = 5.0 Hz, 1H).
[1207] Example 6 (6)
[1208] 3- (2- (pyridin-3-ylmethyloxy) phenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene hydrochloride
[1209]
[1210] TLC: Rf 0.51 (ethyl acetate: methanol: triethylamine = 16: 2: 1);
[1211] _{NMR (DMSO-d 6):} δ 3.70 (dd, J = 15, 2.5Hz, 1H), 3.95 (dd, J = 15, 10Hz, 1H), 5.60 (s, 2H) 5.75 (dd, J = 10, 2H), 7.60-7.90 (m, 5H), 7.95-8.10 (m, 1H), 8.60 (d, J = 7.5Hz, 1H), 7.20-7.35 , 1H), 8.90 (d, J = 5.0 Hz, 1H), 9.05 (s, 1H).
[1212] Example 6 (7)
[1213] 3- (2- (3-hydroxypropyloxy) phenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1214]
[1215] TLC: Rf 0.37 (ethyl acetate);
[1216] _{NMR (CDCl 3): δ 2.00-2.30} (m, 2H), 2.50-2.80 (m, 1H), 3.55 (dd, J = 15, 10Hz, 1H), 3.80 (dd, J = 15, 5.0Hz, 1H ), 3.95 (t, J = 5.0 Hz, 2H), 4.25-4.50 (m, 2H), 5.65 (dd, J = 10, 5.0 Hz, 1H), 7.10-7.20 (m, 2H), 7.60-7.80 m, 4H), 7.80-7.95 (m, 2H).
[1217] Example 6 (8)
[1218] Phenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1219]
[1220] TLC: Rf 0.40 (hexane: AcOEt = 1: 2);
[1221] _{NMR (DMSO-d 6):} δ 1.40 (s, 9H), 3.80 (dd, J = 15, 2.5Hz, 1H), 3.90-4.15 (m, 5H), 5.75 (dd, J = 10, 2.5Hz, 1H), 6.90-7.10 (m, 1H), 7.10 (d, J = 7.5 Hz, 2H), 7.60-7.85 (m, 4H), 7.65 (d, J = 7.5 Hz, 2H).
[1222] Example 6 (9)
[1223] Phenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1224]
[1225] TLC: Rf 0.13 (hexane: AcOEt = 1: 1);
[1226] _{NMR (CDCl 3): δ 1.45} (s, 9H), 3.45-3.55 (m, 2H), 3.70-4.00 (m, 4H), 4.85-5.00 (m, 1H), 5.10 (dd, J = 10, 5.0 Hz, 1 H), 7.00-7.50 (m, 4H), 7.60-7.80 (m, 3H), 8.05 (d, J = 7.5 Hz, 1H).
[1227] Example 7
[1228] 3- (4- (2-aminoethyloxy) phenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene hydrochloride
[1229]
[1230] 4N hydrochloric acid-dioxane solution (10 ml) was added to a solution of the compound (200 mg) prepared in Example 6 (8) in dioxane (25 ml) and methanol (5 ml) at room temperature. The reaction mixture was stirred at room temperature for 30 minutes. The reaction mixture was concentrated to obtain the compound (160 mg) of the present invention having the following physical properties.
[1231] TLC: Rf 0.16 (ethyl acetate: methanol: triethylamine = 16: 3: 1);
[1232] _{NMR (CD 3 OD): δ} 3.35 (t, J = 5.0Hz, 2H), 3.80 (dd, J = 15, 5.0Hz, 1H), 3.95 (dd, J = 15, 10Hz, 1H), 4.30 (t (D, J = 7.5 Hz, 2H), 7.60-8.00 (d, J = (m, 4H).
[1233] Example 7 (1)
[1234] 3- (3- (2-aminoethyloxy) phenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene hydrochloride
[1235]
[1236] The compound prepared in Example 6 (9) was used in place of the compound prepared in Example 6 (8), and the procedure of Example 7 was repeated to give the compound of the present invention having the following physical data.
[1237] TLC: Rf 0.60 (ethyl acetate: methanol: triethylamine = 14: 3: 1);
[1238] _{NMR (CD 3 OD): δ} 3.25-3.45 (m, 2H), 3.80-4.00 (m, 2H), 4.15-4.35 (m, 2H), 5.55 (dd, J = 7.5, 2.5Hz, 1H), 7.20 -7.50 (m, 4H), 7.60-8.00 (m, 4H).
[1239] Example 8
[1240] Phenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene hydrochloride
[1241]
[1242] Sodium cyanoborohydride (86 mg) was added to a mixed solution of acetic acid (3 ml) and methanol (3 ml) of the compound (105 mg) prepared in Example 7 and 90% paraformaldehyde (87 mg) Respectively. The reaction mixture was stirred overnight at room temperature. The reaction mixture was extracted with ethyl acetate with addition of a saturated aqueous sodium hydrogen carbonate solution. The extract was washed with water, dried over anhydrous magnesium sulfate and concentrated. The residue was purified by silica gel column chromatography (ethyl acetate: methanol: triethylamine = 16: 3: 1). To the obtained compound, dioxane (25 ml) and methanol (5 ml) was added 4N hydrochloric acid-dioxane solution (10 ml) at room temperature. The reaction mixture was stirred at room temperature for 30 minutes. The reaction mixture was concentrated to obtain the compound (35 mg) of the present invention having the following physical properties.
[1243] TLC: Rf 0.40 (ethyl acetate: methanol: triethylamine = 16: 3: 1);
[1244] _{NMR (CD 3 OD): δ} 3.10 (s, 6H), 3.60 (t, J = 5.0Hz, 2H), 3.80 (dd, J = 15, 2.5Hz, 1H), 3.95 (dd, J = 15, 10Hz J = 7.5 Hz, 2H), 7.60 (d, J = 7.5 Hz, 2H), 5.50 (dd, J = , &Lt; / RTI &gt; 2H), 7.60-8.00 (m, 4H).
[1245] Example 8 (1)
[1246] Phenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene hydrochloride (salt of 3- (2- (N, N- dimethylamino) ethyloxy)
[1247]
[1248] The compound prepared in Example 7 (1) was used instead of the compound prepared in Example 7, and the procedure of Example 8 was followed to obtain the compound of the present invention having the following physical data.
[1249] TLC: Rf 0.44 (ethyl acetate: methanol: triethylamine = 16: 2: 1);
[1250] _{NMR (DMSO-d 6):} δ 2.80 (s, 6H), 3.50 (t, J = 5.0Hz, 2H), 3.85 (dd, J = 15, 2.5Hz, 1H), 4.00 (dd, J = 15, 1H), 4.30-4.55 (m, 2H), 5.90 (dd, J = 10, 2.5 Hz, 1H), 7.30-7.60 (m, 4H), 7.70-7.90 (m, 4H).
[1251] Example 9
[1252] Nitro-3-phenylthio-2,3-dihydro-1, 1-dioxide benzo [b] thiophene
[1253]
[1254] Nitrobenzothiophene-1,1-dioxide instead of benzothiophene-1,1-dioxide, the compound of the present invention having the following physical properties was obtained.
[1255] TLC: Rf 0.35 (hexane: AcOEt = 2: 1);
[1256] _{NMR (CDCl 3): δ 8.52} (1H, d, J = 2Hz), 8.38 (. 1H, dd J = 8.4, 2.0Hz), 7.89 (1H, d, J = 8.4Hz), 7.48-7.36 (5H, dd, J = 7.6, 6.8 Hz), 4.97 (1H, dd, J = 7.2,6.8Hz), 3.92 (1H, dd, J = 13.6,7.2Hz).
[1257] Example 9 (1) to 9 (17)
[1258] The procedure of Example 9 was repeated except that 5-nitrobenzothiophene-1,1-dioxide was used instead of benzothiophene-1,1-dioxide to obtain the compound of the present invention shown below.
[1259] Example 9 (1)
[1260] 6-methoxy-3-phenylthio-2,3-dihydro-1, 1-dioxide benzo [b] thiophene
[1261]
[1262] TLC: Rf 0.60 (hexane: AcOEt = 1: 1);
[1263] NMR (CDCl ₃ ): 隆 3.52 (dd, J = 13.6 Hz, 6.8 Hz, 1H), 3.81 (dd, J = 13.6 Hz, 6.8 Hz, 1H) 6.8 Hz, 1H), 7.14-7.21 (m, 2H), 7.32-7.40 (m, 3H), 7.40-7.43 (m, 2H), 7.57-7.61 (m, 1H).
[1264] Example 9 (2)
[1265] 3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1266]
[1267] TLC: Rf 0.21 (hexane: dichloromethane = 1: 4);
[1268] _{NMR (CDCl 3): δ 3.60} (dd, J = 14.0Hz, 1.8Hz, 1H), 3.71 (dd, J = 14.0Hz, 6.9Hz, 1H), 3.91 (s, 3H), 5.05 (dd, J = 6.9 Hz, 1.8 Hz, 1H), 7.07 (dd, J = 8.1 Hz, 0.7 Hz, 1H), 7.29-7.37 (m, 4H), 7.48-7.56 (m, 3H).
[1269] Example 9 (3)
[1270] Methoxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1271]
[1272] TLC: Rf 0.62 (hexane: AcOEt = 1: 1);
[1273] _{NMR (CDCl 3): δ 3.51} (dd, 1H, J = 14, 5Hz), 3.79 (dd, 1H, J = 14, 5Hz), 3.88 (s, 3H), 4.92 (t, 1H, J = 5Hz) , 7.04 (dd, IH, J = 5 Hz, 2 Hz), 7.13 (d, IH, J = 2 Hz), 7.35 (m, 3H), 7.44 (m, 2H), 7.63 (d,
[1274] Example 9 (4)
[1275] 7-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1276]
[1277] TLC: Rf 0.42 (hexane: AcOEt = 1: 1);
[1278] _{NMR (CDCl 3): δ 7.62-7.38} (1H, m), 7.58-7.28 (6H, m), 6.79 (1H, d, J = 8.4Hz), 4.89 (1H, t, J = 7.6Hz), 3.97 (3H, s), 3.78 (1H, dd, J = 13.5, 7.6Hz), 3.52 (1H, dd, J = 13.5, 7.6Hz).
[1279] Example 9 (5)
[1280] 4-chloro-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1281]
[1282] TLC: Rf 0.31 (hexane: AcOEt = 2: 1);
[1283] _{NMR (CDCl 3): δ 3.68} (dd, J = 14.2, 3.0Hz, 1H), 3.75 (dd, J = 14.2, 5.6Hz, 1H), 5.00 (dd, J = 5.6, 3.0Hz, 1H), 7.35 -7.40 (m, 3H), 7.49-7.59 (m, 3H), 7.64-7.69 (m, 2H).
[1284] Example 9 (6)
[1285] Methyl-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1286]
[1287] TLC: Rf 0.44 (hexane: AcOEt = 1: 1);
[1288] _{NMR (CDCl 3): δ 1.45} (s, 9H), 3.60 (dd, J = 12.5, 2.5Hz, 1H), 3.75 (dd, J = 12.5Hz, 7.5Hz, 1H), 4.50 (dd, J = 15 , 5.0 Hz, 1H), 4.85 (dd, J = 15, 7.5 Hz, 1H), 5.00-5.20 (m, 2H) 7.30-7.45 (m, 3H), 7.50-7.75 (m,
[1289] Example 9 (7)
[1290] 4,7-dimethyl-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1291]
[1292] TLC: Rf 0.45 (hexane: AcOEt = 2: 1);
[1293] _{NMR (CDCl 3): δ 7.50-7.30} (5H, m), 7.20 (1H, d, J = 7.8Hz), 4.89 (1H, dd, J = 5.8, 2.2Hz), 3.75-3.55 (2H, m) , 2.60 (3 H, s), 2.54 (3 H, s).
[1294] Example 9 (8)
[1295] 4,6-dimethyl-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1296]
[1297] TLC: Rf 0.50 (hexane: AcOEt = 2: 1);
[1298] _{NMR (CDCl 3): δ 7.56-7.24} (7H, m), 4.90 (1H, dd, J = 6.0, 1.8Hz), 3.80-3.66 (2H, m), 2.56 (3H, s), 2.42 (3H, s).
[1299] Example 9 (9)
[1300] 4-Ethyl-3-phenylthio-2,3-dihydro-1,1-dioxo [
[1301]
[1302] TLC: Rf 0.44 (hexane: AcOEt = 2: 1);
[1303] _{NMR (CDCl 3): δ 7.65-7.30} (8H, m), 4.99 (1H, dd, J = 5.9, 2.4Hz), 3.75-3.57 (2H, m), 2.98 (2H, q, J = 7.6Hz) , 1.37 (3H, t, J = 7.6 Hz).
[1304] Example 9 (10)
[1305] Methoxy-5-ethoxycarbonyl-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1306]
[1307] TLC: Rf 0.44 (hexane: AcOEt = 2: 1);
[1308] _{NMR (CDCl 3): δ 7.99} (1H, d, J = 8.0Hz), 7.60-7.50 (3H, m), 7.45-7.35 (3H, m), 5.11 (1H, dd, J = 5.9, 2.8Hz) , 4.45 (2H, q, J = 7.0 Hz), 4.09 (3H, s), 3.75-3.60 (2H, m), 1.44 (3H, t, J = 7.0 Hz).
[1309] Example 9 (11)
[1310] 4-Bromo-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1311]
[1312] TLC: Rf 0.20 (hexane: AcOEt = 3: 1);
[1313] _{NMR (CDCl 3): δ 3.69} (dd, J = 13.9, 2.8Hz, 1H), 3.74 (dd, J = 13.9, 5.3Hz, 1H), 4.94 (dd, J = 5.3, 2.8Hz, 1H), 7.37 J = 7.8 Hz, 1H), 7.57-7.60 (m, 2H), 7.71 (d, J = 7.8 Hz, 1H), 7.84 Hz, 1H).
[1314] Example 9 (12)
[1315] 3-phenylthio-2,3-dihydro-1, 1-dioxide benzo [b] thiophene
[1316]
[1317] TLC: Rf 0.21 (hexane: AcOEt = 1: 1);
[1318] _{NMR (CDCl 3): δ 3.49} (dd, J = 13.9, 5.9Hz, 1H), 3.81 (dd, J = 13.9, 7.5Hz, 1H), 4.93 (dd, J = 7.5, 5.9Hz, 1H), 7.17 (dd, J = 8.0, 0.5 Hz, 1 H), 7.25-7.51 (m, 7H).
[1319] Example 9 (13)
[1320] Hydroxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1321]
[1322] TLC: Rf 0.50 (hexane: AcOEt = 1: 1);
[1323] _{NMR (CDCl 3): δ 3.51} (dd, J = 14.0, 7.0Hz, 1H), 3.78 (dd, J = 14.0,7.0Hz, 1H), 4.89 (t, J = 7.0Hz, 1H), 6.32 (s (M, 2H), 7.58 (d, J = 2.0 Hz, 1H), 6.94 (dd, J = 5.0 Hz, 2.0 Hz, = 5.0 Hz, 1H).
[1324] Example 9 (14)
[1325] Hydroxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1326]
[1327] TLC: Rf 0.28 (hexane: AcOEt = 1: 1);
[1328] _{NMR (CDCl 3): δ 3.54} (dd, J = 13.8, 5.9Hz, 1H), 3.83 (dd, J = 13.8, 7.4Hz, 1H), 4.91 (t- type, J = 6.6Hz, 1H), 7.10 -7.15 (m, 2H), 7.31-7.42 (m, 5H), 7.51-7.56 (m, 1H).
[1329] Example 9 (15)
[1330] Hydroxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1331]
[1332] TLC: Rf 0.52 (hexane: AcOEt = 2: 1);
[1333] _{NMR (CDCl 3): δ 7.50-7.20} (5H, m), 7.11 (1H, d, J = 8.0Hz), 6.85 (1H, d, J = 8.0Hz), 6.68 (1H, dd, J = 32.6, 6.6 Hz), 4.91 (1H, t, J = 7.5 Hz), 3.79 (1H, dd, 14, 7.5 Hz), 3.50 (1H, dd, J = 14, 7.5 Hz).
[1334] Example 9 (16)
[1335] 3-phenylthio-2,3-dihydro-1,1-dioxide thieno [2,3-b] pyridine
[1336]
[1337] TLC: Rf 0.50 (hexane: AcOEt = 1: 1);
[1338] _{NMR (CDCl 3): δ 3.49} (dd, J = 14.0, 7.0Hz, 1H), 3.85 (dd, J = 14.0, 8.0Hz, 1H), 4.91 (dd, J = 8.0, 7.0Hz, 1H), 7.40 (m, 5H), 7.58 (dd, J = 8.0, 5.0 Hz, 1H), 8.08 (m, 1H), 8.76 (m, 1H).
[1339] Example 9 (17)
[1340] 4,7-dihydroxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1341]
[1342] TLC: Rf 0.33 (dichloromethane: ethyl acetate = 1: 1);
[1343] _{NMR (CDCl 3): δ 9.25} (2H, brs), 7.55-7.45 (2H, m), 7.40-7.30 (3H, m), 6.96 (1H, d, J = 8.8Hz), 6.85 (1H, d, J = 8.8 Hz), 5.09 (1H, dd, J = 7.4, 1.6 Hz), 3.71 (1H, dd, 13.9, 7.4 Hz), 3.50 (1H, dd, J = 13.9, 1.6 Hz).
[1344] Example 10
[1345] Nitro-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1346]
[1347] To a solution of the compound prepared in Example 9 (790 mg) in chloroform (45 ml) was added 3-chloroperbenzoic acid (70% purity, 1.21 g) at 0 ° C. The reaction mixture was stirred at room temperature for 2 hours. Water was added to the reaction mixture and extracted with ethyl acetate. The extract was washed sequentially with 2N aqueous sodium hydroxide solution, water and saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate and concentrated. The residue was purified by silica gel column chromatography (hexane: ethyl acetate = 3: 2) to obtain the compound (497 mg) of the present invention having the following physical data.
[1348] TLC: Rf 0.39 (hexane: AcOEt = 1: 1);
[1349] _{NMR (CDCl 3): δ 3.98} (dd, J = 15.5, 3.0Hz, 1H), 4.19 (dd, J = 15.5, 9.3Hz, 1H), 5.95 (dd, J = 9.3, 3.0Hz, 1H), 7.59 J = 8.6 Hz, 1H), 8.41 (d, J = 2.0 Hz, 1H), 8.51 (dd, J = 8.6, 2.0), 7.67-7.67 (m, 2H), 7.78-7.84 Hz, 1H).
[1350] Example 10 (1) to 10 (16)
[1351] The procedure of Example 10 was repeated using the compound prepared in Example 9 (1) to 9 (16) instead of the compound prepared in Example 9 or using oxone instead of 3-chlorobenzoic acid as an oxidizing agent To give the following compounds of the present invention.
[1352] Example 10 (1)
[1353] 6-Methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxo [b] thiophene
[1354]
[1355] TLC: Rf 0.34 (hexane: AcOEt = 1: 1);
[1356] _{NMR (CDCl 3): δ 3.66-3.82} (m, 2H), 3.87 (s, 3H), 5.00 (dd, J = 7.5, 5.5Hz, 1H), 7.06 (d, J = 2.4Hz, 1H), 7.24 (dd, J = 8.8, 2.4 Hz, 1H), 7.46-7.54 (m, 2H), 7.63-7.71 (m, 3H), 7.86 (d, J = 8.8 Hz, 1H).
[1357] Example 10 (2)
[1358] Methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1359]
[1360] TLC: Rf 0.17 (hexane: AcOEt = 1: 1);
[1361] _{NMR (CDCl 3): δ 3.49} (s, 3H), 3.76 (dd, J = 14.9, 9.2Hz, 1H), 4.31 (dd, J = 14.9, 1.3Hz, 1H), 5.23 (dd, J = 9.2, (M, 3H), 7.58-7.68 (m, 1H), 7.72 (d, J = 7.77 (m, 2 H).
[1362] Example 10 (3)
[1363] Methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1364]
[1365] TLC: Rf 0.50 (hexane: AcOEt = 1: 1);
[1366] _{NMR (CDCl 3): δ 3.70} (dd, J = 12, 8Hz, 1H), 3.77 (dd, J = 12, 4Hz, 1H), 3.94 (s, 3H), 5.01 (dd, J = 8, 4Hz, 1H), 7.12 (d, J = 8 Hz, 1H), 7.44 (s, 1H), 7.53 (m, 3H), 7.68 (m, 3H).
[1367] Example 10 (4)
[1368] Methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxo [b] thiophene
[1369]
[1370] TLC: Rf 0.40 (hexane: AcOEt = 1: 2);
[1371] _{NMR (DMSO-d 6):} δ 7.80-7.55 (6H, m), 7.27 (1H, d, J = 8.2Hz), 7.15 (1H, d, J = 8.2Hz), 5.73 (1H, dd, J = (1H, d, J = 15, 3.4 Hz), 3.91 (1H, dd, J = 15, 9.5 Hz), 3.87 (3H, s), 3.69
[1372] Example 10 (5)
[1373] 4-Chloro-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide [
[1374]
[1375] TLC: Rf 0.43 (dichloromethane: ethyl acetate = 15: 1);
[1376] _{NMR (CDCl 3): δ 3.79} (dd, J = 15.0, 9.2Hz, 1H), 4.24 (dd, J = 15.0, 1.0Hz, 1H), 5.26 (dd, J = 9.2, 1.0Hz, 1H), 7.46 -7.66 (m, 6H), 7.77-7.81 (m, 2H).
[1377] Example 10 (6)
[1378] Methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1379]
[1380] TLC: Rf 0.26 (hexane: AcOEt = 1: 1);
[1381] _{NMR (CDCl 3): δ 1.45} (s, 9H), 3.75 (dd, J = 15, 10Hz, 1H), 3.85 (dd, J = 15, 2.5Hz, 1H), 4.40 (dd, J = 15, 5.0 Hz, 1H), 4.95 (dd, J = 15, 7.5 Hz, 1H), 5.35 (m, 2H), 7.45-7.90 (m, 8H).
[1382] Example 10 (7)
[1383] 4,7-dimethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1384]
[1385] TLC: Rf 0.18 (hexane: AcOEt = 2: 1);
[1386] _{NMR (DMSO-d 6):} δ 7.81-7.70 (3H, m), 7.70-7.55 (2H, m), 7.48 (1H, d, J = 7.8Hz), 7.38 (1H, d, J = 7.8Hz) , 5.73 (1H, t, J = 5.2 Hz), 3.84 (2H, d-form, J = 5.2 Hz), 2.40 (3H, s), 2.36 (3H, s).
[1387] Example 10 (8)
[1388] 4,6-dimethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1389]
[1390] TLC: Rf 0.18 (hexane: AcOEt = 2: 1);
[1391] NMR (DMSO-d ₆ ): 7.82-7.70 (3H, m), 7.70-7.55 (2H, m), 7.42 (2H, d, J = 5.4Hz) , 3.86-3.80 (2H, m), 2.38 (6H, s).
[1392] Example 10 (9)
[1393] 4-ethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxo [b] thiophene
[1394]
[1395] TLC: Rf 0.22 (hexane: AcOEt = 2: 1);
[1396] _{NMR (CDCl 3): δ 7.68-7.40} (8H, m), 5.22 (1H, d, J = 9.2Hz), 3.99 (1H, d, J = 15.2Hz), 3.76 (1H, dd, J = 15.2, 9.2 Hz), 3.07 (2H, dq, J = 7.6,2.2Hz), 1.33 (3H, t, J = 7.6Hz).
[1397] Example 10 (10)
[1398] Methoxy-5-ethoxycarbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1399]
[1400] TLC: Rf 0.38 (hexane: AcOEt = 1: 1);
[1401] _{NMR (CDCl 3): δ 7.91} (1H, d, J = 8.0Hz), 7.83-7.45 (5H, m), 7.41 (1H, d, J = 8.0Hz), 5.28 (1H, d- type, J = D, J = 15, 1.6 Hz), 3.86 (3H, s), 3.75 (1H, dd, J = , 1.43 (3H, t, J = 7.0 Hz).
[1402] Example 10 (11)
[1403] 4-Bromo-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1404]
[1405] TLC: Rf 0.35 (hexane: AcOEt = 1: 1);
[1406] _{NMR (CDCl 3): δ 3.79} (dd, J = 15.0, 9.2Hz, 1H), 4.23 (dd, J = 15.0, 1.1Hz, 1H), 5.23 (d- type, J = 8.8Hz, 1H), 7.44 -7.54 (m, 3H), 7.62-7.70 (m, 2H), 7.78-7.83 (m, 3H).
[1407] Example 10 (12)
[1408] 3-phenylsulfonyl-2, 3-dihydro-1, 1-dioxo [b] thiophene
[1409]
[1410] TLC: Rf 0.22 (hexane: AcOEt = 1: 2);
[1411] _{NMR (DMSO-d 6):} δ 3.96 (dd, J = 15.0, 8.4Hz, 1H), 4.08 (dd, J = 15.0, 1.8Hz, 1H), 5.51 (dd, J = 8.4, 1.8Hz, 1H) , 7.00 (d-form, J = 8.0 Hz, 1H), 7.16 (d, J = 7.0 Hz, 1H), 7.47 (t, J = 8.0 Hz, 1H), 7.56-7.63 7.81 (m, 3H).
[1412] Example 10 (13)
[1413] Hydroxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1414]
[1415] TLC: Rf 0.30 (hexane: AcOEt = 1: 1);
[1416] _{NMR (DMSO-d 6):} δ 3.66 (dd, J = 14, 4Hz, 1H), 3.90 (dd, J = 14, 9Hz, 1H), 5.71 (dd, J = 9, 4Hz, 1H), 7.07 ( m, 2H), 7.55-7.82 (m, 6H), 10.80 (br s, 1H).
[1417] Example 10 (14)
[1418] 3-phenylsulfonyl-2, 3-dihydro-1, 1-dioxo [b] thiophene
[1419]
[1420] TLC: Rf 0.37 (hexane: AcOEt = 1: 2);
[1421] _{NMR (DMSO-d 6):} δ 3.73 (dd, J = 15.2, 3.2Hz, 1H), 3.96 (dd, J = 15.2, 9.2Hz, 1H), 5.60 (dd, J = 9.2, 3.2Hz, 1H) , 6.54 (d, J = 8.4 Hz, 1H), 7.57-7.64 (m, 2H), 7.71-7.76 (m, , 3H).
[1422] Example 10 (15)
[1423] 3-phenylsulfonyl-2, 3-dihydro-1, 1-dioxo [b] thiophene
[1424]
[1425] TLC: Rf 0.31 (hexane: AcOEt = 1: 2);
[1426] _{NMR (DMSO-d 6):} δ 7.80-7.45 (6H, m), 6.98 (2H, d, J = 8.4Hz), 5.66 (1H, dd, J = 9.6, 3.2Hz), 3.85 (1H, dd, J = 15, 9.6 Hz), 3.68-3.58 (1H, m).
[1427] Example 10 (16)
[1428] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxo thieno [2,3-b] pyridine
[1429]
[1430] TLC: Rf 0.20 (hexane: AcOEt = 1: 1);
[1431] _{NMR (CDCl 3): δ 3.65} (dd, J = 15, 8Hz, 1H), 3.74 (dd, J = 15, 6Hz, 1H), 5.04 (dd, J = 8, 6Hz, 1H), 7.58 (m, 2H), 7.69 (m, 4H), 8.48 (m, 1H), 8.86 (m, 1H).
[1432] Example 11
[1433] 5-amino-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1434]
[1435] 5% palladium-carbon (20 mg) was added to a solution of the compound (110 mg) prepared in Example 10 in ethanol (7.5 ml) and ethyl acetate (7.5 ml) under an argon atmosphere. The reaction mixture was stirred under hydrogen atmosphere at room temperature for 2 hours. The reaction mixture was filtered through Celite (trade name), and the filtrate was concentrated. The residue was purified by silica gel column chromatography (dichloromethane: ethyl acetate = 2: 1) to obtain the compound (94 mg) of the present invention having the following physical data. Further, the compound of the present invention having the following physical properties was also obtained by conversion into the corresponding salt by a known method.
[1436] Free body:
[1437] TLC: Rf 0.29 (hexane: AcOEt = 1: 2);
[1438] _{NMR (CDCl 3): δ 3.61} (dd, J = 14.6, 8.3Hz, 1H), 3.70 (dd, J = 14.6, 5.6Hz, 1H), 4.34 (brs, 2H), 4.94 (dd, J = 8.3, J = 8.0 Hz, 1H), 7.49-7.55 (m, 1H), 6.79 (dd, J = 8.0, 2.0 Hz, 1H) 2H), 7.63-7. 74 (m, 3H).
[1439] Hydrochloride:
[1440] TLC: Rf 0.47 (dichloromethane: methanol = 18: 1);
[1441] _{NMR (DMSO-d 6):} δ 3.53 (dd, J = 14.9, 3.8Hz, 1H), 3.75 (dd, J = 14.9, 9.4Hz, 1H), 5.58 (dd, J = 9.4, 3.8Hz, 1H) J = 8.6 Hz, 1H), 7.57-7.65 (m, 2H), 7.72 (d, J = 7.79 (m, 3 H).
[1442] Example 12
[1443] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1444]
[1445] Acetic anhydride (1 ml) was added to a pyridine (2 ml) solution of the compound (91 mg) prepared in Example 11. The reaction mixture was stirred at room temperature for 2 hours. The reaction mixture was concentrated. The residue was purified by silica gel column chromatography (hexane: ethyl acetate = 1: 1) to obtain the present compound (86 mg) having the following physical data.
[1446] TLC: Rf 0.20 (hexane: AcOEt = 1: 2);
[1447] _{NMR (CDCl 3): δ 2.24} (s, 3H), 3.66 (dd, J = 14.8, 8.3Hz, 1H), 3.75 (dd, J = 14.8, 5.2Hz, 1H), 5.04 (dd, J = 8.3, 5.2 Hz, 1H), 7.49-7.59 (m, 3H), 7.66-7.75 (m, 3H), 7.87-7.94 (m, 2H), 8.04 (s-
[1448] Example 13
[1449] 4-Aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene hydrochloride
[1450]
[1451] The compound prepared in Example 10 (6) was used in place of the compound prepared in Example 6 (8), and the procedure of Example 7 was followed to obtain the compound of the present invention having the following physical data.
[1452] TLC: Rf 0.16 (ethyl acetate: methanol: triethylamine = 16: 2: 1);
[1453] _{NMR (DMSO-d 6):} δ 3.80-4.00 (m, 2H), 4.35 (d, J = 15Hz, 1H), 4.55 (d, J = 15Hz, 1H), 6.30-6.40 (m, 1H), 7.60 -7.70 (m, 2H), 7.75-7.95 (m, 5H), 8.00-8.15 (m, 1H), 8.30-8.65 (m, 2H).
[1454] Example 14
[1455] Dimethylamino) methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene hydrochloride
[1456]
[1457] Using the compound prepared in Example 13 instead of the compound prepared in Example 7, the procedure of Example 8 was repeated to give the compound of the present invention having the following physical data.
[1458] TLC: Rf 0.50 (ethyl acetate: methanol: triethylamine = 16: 2: 1);
[1459] _{NMR (DMSO-d 6):} δ 2.65 and 2.70 (both s, total 3H), 2.85 and 2.90 (both s, total 3H), 3.80 (d, J = 12.5Hz, 1H), 4.05 (dd, J = 12.5 , 7.5 Hz, 1H), 4.50-4.70 (m, 1H), 4.70-4.90 (m, 1H), 6.35 (d, J = 7.5 Hz, 1H), 7.60-8.00 (m, 7H), 8.20-8.35 m, 1 H), 10.85 (brs, 1 H).
[1460] Example 15
[1461] Methoxy-5-formyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1462]
[1463] A tetrahydrofuran (10 ml) solution of the compound (300 mg) prepared in Example 10 (10) was added dropwise to a tetrahydrofuran (10 ml) suspension of lithium aluminum hydride (54 mg) at -78 캜. And the mixture was stirred at the same temperature for 1 hour. Ice water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed successively with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and concentrated. The residue was purified by silica gel column chromatography (hexane: ethyl acetate = 1: 1) to give the inventive compound (51 mg) having the following physical data.
[1464] TLC: Rf 0.27 (hexane: AcOEt = 1: 2);
[1465] NMR (CDCl ₃ ): 隆 3.80 (dd, J = 15.2,9.3 Hz, 1H), 4.05 (s, 3H), 4.14 (dd, J = 15.2, 1.4 Hz, 1H), 5.28 (M, 3H), 8.05 (d, J = 8.0 Hz, 1H), 10.33 (d, J = 0.6 Hz, 1H).
[1466] Example 16
[1467] Methoxy-3- (thiophen-2-yl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1468]
[1469] The procedure of Example 1 was repeated using 2-thiophenetiol and 4-methoxybenzothiophene-1,1-dioxide to obtain the compound of the present invention having the following physical properties.
[1470] TLC: Rf 0.27 (dichloromethane: hexane = 4: 1);
[1471] _{NMR (CDCl 3): δ 3.66} (d, J = 15.5, 5.4Hz, 1H), 3.73 (dd, J = 15.5, 4.2Hz, 1H), 3.95 (s, 3H), 4.88 (dd, J = 5.4, 7.29 (d, J = 8.0 Hz, 1H), 7.09 (dd, J = 5.4, 3.6 Hz, 1H) J = 8.0 Hz, 1H), 7.44 (dd, J = 5.4,1.2 Hz, 1H), 7.53 (t, J = 8.0 Hz, 1H).
[1472] Example 17
[1473] Methoxy-3- (thiophen-2-yl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1474]
[1475] Using the compound prepared in Example 16 instead of the compound prepared in Example 9, the procedure of Example 10 was repeated to give the compound of the present invention having the following physical data.
[1476] TLC: Rf 0.46 (dichloromethane: ethyl acetate = 10: 1);
[1477] _{NMR (CDCl 3): δ 3.73} (s, 3H), 3.79 (dd, J = 15.0, 9.2Hz, 1H), 4.23 (dd, J = 15.0, 1.2Hz, 1H), 5.32 (dd, J = 9.2, J = 8.0 Hz, 1H), 7.53 (dd, J = 8.0 Hz, 1H), 7.04 3.8, 1.4 Hz, 1H), 7.59 (t, J = 8.0 Hz, 1H), 7.73 (dd, J = 4.9, 1.4 Hz, 1H).
[1478] Example 18
[1479] 3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1480]
[1481] 4-nitrobenzyl bromide (947 mg) and potassium carbonate (1.0 g) were added to a solution of the compound (1.0 g) prepared in Example 9 (12) in dimethylformamide (30 ml). The reaction mixture was stirred overnight at room temperature. Water was added to the reaction mixture and extracted with ethyl acetate. The extract was washed with water (x3), saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and concentrated. The residue was purified by silica gel column chromatography (hexane: ethyl acetate = 1: 1) to give the compound (1.1 g) of the present invention having the following physical data.
[1482] TLC: Rf 0.29 (hexane: AcOEt = 1: 1);
[1483] _{NMR (CDCl 3): δ 8.25} (2H, d, J = 8.5Hz), 7.71 (2H, d, J = 8.5Hz), 7.60-7.20 (7H, m), 7.10 (1H, d, J = 8Hz) , 5.32 (2H, s), 5.11 (1H, dd, J = 7,2Hz), 3.85-3.55 (2H, m).
[1484] Example 18 (1) to 18 (40)
[1485] The compound of the present invention shown below was obtained by operating in the same manner as in Example 18 using the compound prepared in Example 9 (12) to 9 (15) or Example 9 (17) and the corresponding halide.
[1486] Example 18 (1)
[1487] 3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1488]
[1489] TLC: Rf 0.27 (hexane: AcOEt = 2: 1);
[1490] _{NMR (CDCl 3): δ 7.54-7.42} (3H, m), 7.32-7.19 (6H, m), 7.10 (1H, d, J = 8.0Hz), 6.95-6.84 (3H, m), 5.01 (1H, dd, J = 6.6,2.2Hz), 4.31 (2H, t, J = 6.0Hz), 4.20 (2H, t, J = 6.0Hz), 3.69 1H, dd, J = 13.9,2.2Hz), 2.31 (2H, quintet, J = 6.0Hz).
[1491] Example 18 (2)
[1492] Benzyloxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1493]
[1494] TLC: Rf 0.45 (hexane: AcOEt = 2: 1);
[1495] _{NMR (CDCl 3): δ 7.54-7.26} (12H, m), 7.13 (1H, d, J = 9.0Hz), 5.22 (2H, s), 5.03 (1H, dd, J = 6.0, 2.6Hz), 3.71 (1H, dd, J = 13.8, 6.0 Hz), 3.63 (1H, dd, J = 13.8, 2.6 Hz).
[1496] Example 18 (3)
[1497] 3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1498]
[1499] TLC: Rf 0.47 (hexane: AcOEt = 1: 1);
[1500] _{NMR (CDCl 3): δ 2.13} (5 quint, J = 6.0Hz, 2H), 3.58 (dd, J = 14.0, 2.4Hz, 1H), 3.67 (dd, J = 14.0, 6.6Hz, 1H), 3.69 ( J = 6.0 Hz, 2H), 4.22 (t, J = 6.0 Hz, 2H), 4.44 (d, J = 12.0 Hz, 1H) J = 6.6, 2.4 Hz, 1H), 7.08 (d-form, J = 7.4 Hz, 1H), 7.26 (s, 5H), 7.30-7.35 (m, 4H), 7.43-7.54 (m, 3H).
[1501] Example 18 (4)
[1502] 3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1503]
[1504] TLC: Rf 0.46 (ethyl acetate);
[1505] _{NMR (CDCl 3): δ 3.62} (dd, J = 14.0, 2.2Hz, 1H), 3.72 (dd, J = 14.0, 6.2Hz, 1H), 5.04 (dd, J = 6.2, 2.2Hz, 1H), 5.23 (s, 2H), 7.15 (dd, J = 8.0,1.0 Hz, 1H), 7.26-7.45 (m, 7H), 7.54 (t, J = 8.0 Hz, 1H), 7.85-7.92 8.63 (dd, J = 4.7, 2.0 Hz, 1H), 8.76 (dd, J = 2.0, 0.6 Hz, 1H).
[1506] Example 18 (5)
[1507] 2-ylmethyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1508]
[1509] TLC: Rf 0.25 (hexane: AcOEt = 1: 1);
[1510] _{NMR (CDCl 3): δ 8.18} (1H, d, J = 8Hz), 8.10 (1H, d, J = 8Hz), 7.92-7.68 (3H, m), 7.68-7.40 (4H, m), 7.40-7.22 (2H, s), 5.18 (1H, dd, J = 7,2Hz), 3.76 (1H, dd, J = 14,7Hz), 7.16 (1H, d, J = 3.66 (1H, dd, J = 14,2Hz).
[1511] Example 18 (6)
[1512] 2-ylmethyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1513]
[1514] TLC: Rf 0.33 (ethyl acetate);
[1515] _{NMR (CDCl 3): δ 8.62} (1H, d, J = 5Hz), 7.80-7.58 (2H, m), 7.58-7.38 (3H, m), 7.38-7.18 (5H, m), 7.11 (1H, d , J = 8 Hz), 5.35 (2H, s), 5.15 (1H, dd, J = 7, 2 Hz), 3.85-3.58 (2H, m).
[1516] Example 18 (7)
[1517] 3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1518]
[1519] TLC: Rf 0.15 (ethyl acetate);
[1520] _{NMR (CDCl 3): δ 8.78-8.55} (2H, m), 7.65-7.18 (9H, m), 7.07 (1H, d, J = 8Hz), 5.23 (2H, s), 5.11 (1H, dd, J = 7, 2 Hz), 3.82-3.53 (2H, m).
[1521] Example 18 (8)
[1522] 3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1523]
[1524] TLC: Rf 0.18 (ethyl acetate);
[1525] _{NMR (CDCl 3): δ 8.48-8.35} (m, 2H), 7.67-7.33 (m, 9H), 6.95 (d, J = 8.0Hz, 1H), 5.01 (d- type, J = 8.5Hz, 1H) , 4.15-3.86 (m, 4H), 2.81 (t, J = 7.0 Hz, 2H), 2.21-2.01 (m, 2H).
[1526] Example 18 (9)
[1527] 3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1528]
[1529] TLC: Rf 0.24 (hexane: AcOEt = 1: 2);
[1530] _{NMR (CDCl 3): δ 2.06-2.17} (m, 2H), 3.57 (dd, J = 14.0, 2.2Hz, 1H), 3.67 (dd, J = 14.0, 6.6Hz, 1H), 3.91 (br, 2H) (D, J = 6.6, 2.2 Hz, 1H), 7.11 (d, J = 8.0 Hz, 1H), 7.30-7.38 (m, 4H), 7.49 7.56 (m, 3 H).
[1531] Example 18 (10)
[1532] 5-Pentoxy-3-phenylthio-2,3-dihydro-1, 1-dioxide [
[1533]
[1534] TLC: Rf 0.70 (hexane: AcOEt = 2: 1);
[1535] _{NMR (CDCl 3): δ 0.95} (t, J = 7.0Hz, 3H), 1.38-1.47 (m, 4H), 1.82 (5 quint, J = 6.8Hz, 2H), 3.51 (dd, J = 15, 7Hz J = 6.8 Hz, 2H), 4.89 (t, J = 7.0 Hz, 1H), 7.01 (dd, J = 2H), 7.61 (d, J = 8 Hz, 1 H), 7.12 (d, J = 2 Hz, 1 H), 7.36-7.38 (m, 3H), 7.41-7.43 (m,
[1536] Example 18 (11)
[1537] 3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1538]
[1539] TLC: Rf 0.75 (hexane: AcOEt = 1: 1);
[1540] _{NMR (CDCl 3): δ 7.65} (1H, d, J = 8.5Hz), 7.45-7.42 (2H, m), 7.34-7.29 (5H, m), 7.21 (1H, d, J = 2.2Hz), 7.09 (1H, d, J = 8.5, 2.2 Hz), 7.00 (1H, t, J = 7.0 Hz), 6.95 (4H, m), 3.78 (1H, dd, J = 14.0, 7.0Hz), 3.52 (1H, dd, J = 14.0, 7.0Hz).
[1541] Example 18 (12)
[1542] 3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1543]
[1544] TLC: Rf 0.25 (hexane: AcOEt = 1: 1);
[1545] _{NMR (CDCl 3): δ 2.10} (5 quint, J = 6.5Hz, 2H), 3.60 (dd, J = 14, 6.7Hz, 1H), 3.82 (dd, J = 14, 6.7Hz, 1H), 3.89 ( J = 6.5 Hz, 2H), 4.20 (t, J = 6.5 Hz, 2H), 4.98 (t, J = 6.7 Hz, 1H), 7.20 7.47 (m, 6H), 7.61 (d, J = 8.5 Hz, 1 H).
[1546] Example 18 (13)
[1547] 3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1548]
[1549] TLC: Rf 0.40 (ethyl acetate);
[1550] NMR (CDCl ₃ ): 隆 3.51 (dd, J = 9.0, 4.5 Hz, 1H), 3.79 (dd, J = 9.0, 5.0 Hz, 1H) (d, J = 5.6 Hz, 1H), 7.21 (d, J = 1.6 Hz, 1H), 7.33-7.42 (m, 6H), 7.65 1H), 7.77 (dt, J = 5.4, 1.3 Hz, 1H), 8.63 (dd, J = 3.2, 1.3 Hz, 1H), 8.70 (d, J = 1.3 Hz, 1H).
[1551] Example 18 (14)
[1552] 3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1553]
[1554] TLC: Rf 0.16 (ethyl acetate);
[1555] _{NMR (CDCl 3): δ 8.36-8.28} (m, 2H), 7.78-7.55 (m, 4H), 7.42-7.36 (m, 5H), 7.01 (d, J = 8.0Hz, 1H), 5.11 (d- J = 7.0Hz, 2H), 2.35-2.26 (m, 2H, J = 9.0Hz, 1H), 4.12 (t, J = 7.0Hz, 2H), 3.88-3.64 ).
[1556] Example 18 (15)
[1557] 3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1558]
[1559] TLC: Rf 0.42 (hexane: AcOEt = 2: 1);
[1560] NMR (CDCl ₃ ): 7.61-7.56 (1H, m), 7.43-7.25 (7H, m), 7.19-7.15 (2H, m), 6.95-6.89 J = 6.6 Hz), 4.22 (2H, t, J = 6.0 Hz), 4.15 (2H, t, J = 6.0 Hz), 3.80 (1H, dd, J = , J = 13.8, 7.3 Hz), 2.28 (2H, quintet, J = 6.0 Hz).
[1561] Example 18 (16)
[1562] Benzyloxy-3-phenylthio-2,3-dihydro-1, 1-dioxide benzo [b] thiophene
[1563]
[1564] TLC: Rf 0.58 (hexane: AcOEt = 2: 1);
[1565] NMR (CDCl ₃ ): 7.63-7.58 (1H, m), 7.45-7.31 (10H, m), 7.27-7.23 = 6.7 Hz), 3.81 (1H, dd, J = 13.7, 7.5 Hz), 3.52 (1H, dd, J = 13.7, 6.1 Hz).
[1566] Example 18 (17)
[1567] 6-pentoxy-3-phenylthio-2,3-dihydro-1, 1-dioxide [
[1568]
[1569] TLC: Rf 0.51 (hexane: AcOEt = 2: 1);
[1570] _{NMR (CDCl 3): δ 7.60-7.55} (1H, m), 7.43-7.31 (5H, m), 7.19-7.12 (2H, m), 4.91 (1H, t, J = 6.8Hz), 3.99 (2H, (1H, d, J = 6.6 Hz), 3.80 (1H, dd, J = 13.8, 7.3 Hz), 3.51 -1.30 (4H, m), 0.92 (3H, t, J = 7.0 Hz).
[1571] Example 18 (18)
[1572] 3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1573]
[1574] TLC: Rf 0.41 (hexane: ethyl acetate: triethylamine = 2: 4: 1);
[1575] _{NMR (CDCl 3): δ 7.60} (1H, d, J = 8.4Hz), 7.42-7.32 (5H, m), 7.22-7.16 (2H, m), 4.92 (1H, t- type, J = 6.8Hz) , 4.15 (2H, t, J = 5.8 Hz), 3.81 (1H, dd, J = 13.8, 7.2 Hz), 3.73 , 6.1 Hz), 2.82 (2H, t, J = 5.8 Hz), 2.57 (4H, t-form, J = 4.6 Hz).
[1576] Example 18 (19)
[1577] 6 - (3-hydroxypropyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1578]
[1579] TLC: Rf 0.33 (hexane: AcOEt = 1: 2);
[1580] _{NMR (CDCl 3): δ 2.06} (5 quint, J = 6.1Hz, 2H), 3.51 (dd, J = 13.6, 6.2Hz, 1H), 3.80 (dd, J = 13.6, 7.4Hz, 1H), 3.85 ( J = 6.8 Hz, 1H), 7.16-7.21 (m, 2H), 7.32-7.45 (m, 2H), 4.17 , &Lt; / RTI &gt; 5H), 7.57-7.61 (m, 1H).
[1581] Example 18 (20)
[1582] 3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1583]
[1584] TLC: Rf 0.31 (dichloromethane: ethyl acetate = 2: 1);
[1585] _{NMR (CDCl 3): δ 3.53} (dd, J = 13.6, 6.2Hz, 1H), 3.82 (dd, J = 13.6, 7.2Hz, 1H), 4.93 (t- type, J = 6.6Hz, 1H), 5.12 (m, 2H), 7.23-7.28 (m, 2H), 7.33-7.46 (m, 6H), 7.61-7.65 1.6 Hz, 1 H), 8.70 (d, J = 1.6 Hz, 1 H).
[1586] Example 18 (21)
[1587] 6- (3-nitrophenylmethyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1588]
[1589] TLC: Rf 0.49 (hexane: AcOEt = 1: 1);
[1590] _{NMR (CDCl 3): δ 8.33} (1H, brs), 8.22 (1H, dd, J = 8, 2Hz), 7.76 (1H, d, J = 7.8Hz), 7.70-7.48 (2H, m), 7.48- (1H, d, J = 6.8Hz), 3.83 (1H, dd, J = 13.6, 7.6Hz), 3.54 13.6, 6.2 Hz).
[1591] Example 18 (22)
[1592] 3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1593]
[1594] TLC: Rf 0.48 (hexane: AcOEt = 3: 1);
[1595] _{NMR (CDCl 3): δ 2.35} (5 quint, J = 7.5Hz, 2H), 3.55 (t, J = 7.5Hz, 2H), 3.59 (dd, J = 15, 7Hz, 1H), 3.80 (dd, J J = 7 Hz, 1H), 7.20 (dd, J = 9, 2 Hz, 1H), 7.34-7.43 (m, 6H), 7.60 (d, J = 9 Hz, 1 H).
[1596] Example 18 (23)
[1597] 7-pentoxy-3-phenylthio-2,3-dihydro-1,1-dioxo [b] thiophene
[1598]
[1599] TLC: Rf 0.80 (hexane: AcOEt = 1: 1);
[1600] NMR (CDCl ₃ ): 隆 7.54 (1H, t, J = 7.8 Hz), 7.45-7.21 (6H, m), 6.91 D, J = 13.6, 7.6 Hz), 1.87 (2H, quintet, J), 4.11 (2H, t, J = 7.0 Hz), 3.77 (1H, dd, J = = 7.0 Hz), 1.50-1.30 (4H, m), 0.92 (3H, t, J = 7.2 Hz).
[1601] Example 18 (24)
[1602] 3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1603]
[1604] TLC: Rf 0.55 (hexane: AcOEt = 1: 1);
[1605] NMR (CDCl ₃ ): 隆 7.58 (1H, t, J = 7.8 Hz), 7.45-7.25 (8H, m), 7.06 (1H, d, J = 8.4 Hz), 7.05-6.90 (1H, d, J = 7.6Hz), 4.58-4.45 (2H, m), 4.45-4.35 = 13.6, 7.6 Hz).
[1606] Example 18 (25)
[1607] 3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1608]
[1609] TLC: Rf 0.25 (hexane: AcOEt = 1: 2);
[1610] _{NMR (CDCl 3): δ 7.60-6.60} (8H, m), 4.90 (1H, t, J = 6.8Hz), 4.36-4.26 (2H, m), 3.90 (2H, br) 3.79 (1H, d, J = 13.8, 6.8 Hz), 3.52 (1H, dd, J = 13.8, 6.8 Hz), 2.50-2.05 (2H, m).
[1611] Example 18 (26)
[1612] 3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1613]
[1614] TLC: Rf 0.12 (hexane: AcOEt = 1: 2);
[1615] _{NMR (CDCl 3): δ 8.66} (1H, d, J = 2.2Hz), 8.57 (1H, dd, J = 4.8, 1.8Hz), 7.93 (1H, d, J = 8.2Hz), 7.56 (1H, t (1H, d, J = 8.2 Hz), 7.45-7.30 (4H, m), 6.97 , dd, J = 13.8, 7.8 Hz), 3.54 (1H, dd, J = 13.8, 7.8 Hz).
[1616] Example 18 (27)
[1617] 3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1618]
[1619] TLC: Rf 0.33 (hexane: AcOEt = 2: 1);
[1620] _{NMR (CDCl 3): δ 7.57-7.46} (3H, m), 7.37-7.32 (4H, m), 6.93 (1H, d- type, J = 8.0Hz), 5.16 ( 1H, dd, J = 6.6, 2.0 Hz), 4.61 (2H, s), 3.72 (1H, dd, J = 13.9,6.6Hz), 3.61 (1H, dd, J = 13.9,2.0Hz), 1.49 (9H, s).
[1621] Example 18 (28)
[1622] 3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1623]
[1624] TLC: Rf 0.52 (hexane: AcOEt = 2: 1);
[1625] _{NMR (CDCl 3): δ 1.50} (s, 9H), 3.48 (dd, J = 14, 6.7Hz, 1H), 3.82 (dd, J = 14, 6.7Hz, 1H), 4.66 (s, 2H), 4.95 (t, J = 6.7 Hz, 1H), 7.18 (dd, J = 9, 2.3 Hz, 1H) 7.40-7.53 (m, 6H), 7.62 (d, J = 9 Hz, 1H).
[1626] Example 18 (29)
[1627] 6-t-butoxycarbonylmethyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1628]
[1629] TLC: Rf 0.44 (hexane: AcOEt = 2: 1);
[1630] _{NMR (CDCl 3): δ 7.61} (1H, d, J = 8.7Hz), 7.44-7.32 (5H, m), 7.24 (1H, dd, J = 8.7, 2.6Hz), 7.08 (1H, d, J = Dd, J = 13.7, 6.1Hz), 4.91 (1H, t-form, J = 6.7Hz), 4.56 (2H, s), 3.80 Hz), 1.49 (9 H, s).
[1631] Example 18 (30)
[1632] 3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1633]
[1634] TLC: Rf 0.55 (hexane: AcOEt = 1: 1);
[1635] NMR (CDCl ₃ ): 隆 7.54 (1H, t, J = 7.6Hz), 7.45-7.27 (6H, m), 6.80 ), 4.69 (2H, s), 3.79 (1H, dd, J = 13.6, 7.6Hz), 3.52 (1H, dd, J = 13.6, 7.6Hz), 1.46 (9H, s).
[1636] Example 18 (31)
[1637] 3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1638]
[1639] TLC: Rf 0.35 (hexane: AcOEt = 1: 2);
[1640] _{NMR (CDCl 3): δ 1.35} (s, 9H), 3.46-3.66 (m, 2H), 3.62 (dd, J = 14.2, 2.2Hz, 1H), 3.73 (dd, J = 14.2, 6.8Hz, 1H) , 4.39-4.25 (m, 2H), 5.06 (dd, J = 6.8,2.2Hz, 1H) ), 7.44-7.57 (m, 3H).
[1641] Example 18 (32)
[1642] 3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1643]
[1644] TLC: Rf 0.28 (hexane: AcOEt = 1: 1);
[1645] NMR (CDCl ₃ ): 1.38 (s, 9H), 2.00-2.11 (m, 2H), 3.33-3.44 (m, 2H), 3.59 (dd, J = 14.0, 2.2Hz, J = 6.6, 2.2 Hz, 1H), 7.08 (dd, J = 8.1 Hz, 1H) , 0.7 Hz, 1 H), 7.29-7.38 (m, 4H), 7.48-7.56 (m, 3H).
[1646] Example 18 (33)
[1647] 3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene (2-t-butoxycarbonylamino)
[1648]
[1649] TLC: Rf 0.40 (hexane: AcOEt = 2: 1);
[1650] _{NMR (CDCl 3): δ 1.46} (s, 9H), 3.52 (dd, J = 15, 6Hz, 1H), 3.56 (t, J = 7.5Hz, 2H), 3.80 (dd, J = 15, 6Hz, 1H (D, J = 9 Hz, 2H), 4.12 (t, J = 7.5 Hz, 2H), 4.88 = 2 Hz, 1H), 7.35-7.47 (m, 5H), 7.64 (d, J = 9 Hz, 1H).
[1651] Example 18 (34)
[1652] 3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene (6-t-butoxycarbonylamino)
[1653]
[1654] TLC: Rf 0.43 (hexane: AcOEt = 1: 1);
[1655] _{NMR (CDCl 3): δ 1.44} (s, 9H), 2.01 (5 quint, J = 6.2Hz, 2H), 3.32 (q, J = 6.2Hz, 2H), 3.51 (dd, J = 13.6, 6.0Hz, 1H), 3.80 (dd, J = 13.6, 7.4 Hz, 1H), 4.06 (t, J = 6.2 Hz, 2H) 7.14-7.21 (m, 2H), 7.32-7.45 (m, 5H), 7.59 (d, J = 8.4 Hz, 1H).
[1656] Example 18 (35)
[1657] 3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene (6-t-butoxycarbonylamino)
[1658]
[1659] TLC: Rf 0.47 (hexane: AcOEt = 1: 1);
[1660] _{NMR (CDCl 3): δ 1.46} (s, 9H), 3.51 (dd, J = 13.8, 6.2Hz, 1H), 3.55 (q, J = 5.2Hz, 2H), 3.81 (dd, J = 13.8, 7.4Hz (T, J = 6.4 Hz, 1H), 4.96 (br, 1H), 7.13 (d, J = 2.4 Hz, 1H), 7.18 (dd, J = 8.5, 2.4 Hz, 1H), 7.32-7.45 (m, 5H), 7.60 (d, J = 8.5 Hz, 1H).
[1661] Example 18 (36)
[1662] 3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1663]
[1664] TLC: Rf 0.60 (hexane: AcOEt = 1: 2);
[1665] _{NMR (CDCl 3): δ 7.60-7.24} (7H, m), 6.94 (1H, d, J = 8.4Hz), 5.38 (1H, bs), 4.90 (1H, t, J = 7.4Hz), 4.30-4.05 (2H, m), 3.79 (1H, dd, J = 13.7,7.4Hz), 3.60-3.40 (3H, m), 1.42 (9H, s).
[1666] Example 18 (37)
[1667] 3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1668]
[1669] TLC: Rf 0.41 (hexane: AcOEt = 1: 1);
[1670] _{NMR (CDCl 3): δ 7.60-7.42} (3H, m), 7.42-7.25 (4H, m), 7.04 (1H, d, J = 8.2Hz), 5.05 (1H, dd, J = 6.6, 2.2Hz) , 4.80-4.60 (1H, m), 3.85-3.32 (6H, m), 2.15-1.65 (4H, m), 1.48 (9H, s).
[1671] Example 18 (38)
[1672] 3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene (4-hydroxyphenyl)
[1673]
[1674] TLC: Rf 0.35 (hexane: AcOEt = 1: 2);
[1675] _{NMR (CDCl 3): δ 7.53-7.30} (5H, m), 7.20-6.85 (2H, m), 5.40 (2H, brs), 5.03-4.85 (1H, m), 4.25-4.00 (4H, m), 3.90-3.40 (6H, m), 1.43 (18H, s).
[1676] Example 18 (39)
[1677] 3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1678]
[1679] TLC: Rf 0.29 (hexane: AcOEt = 1: 1);
[1680] _{NMR (CDCl 3): δ 8.44} (1H, s), 8.24 (1H, d, J = 8.4Hz), 7.86 (1H, d, J = 8.0Hz), 7.65-7.20 (8H, m), 7.14 (1H (d, J = 7.2 Hz), 5.31 (2H, s), 5.13 (1H, dd, J = 2.6 Hz, 6.6 Hz), 3.80-3.56 (2H, m).
[1681] Example 18 (40)
[1682] 4,7-bis (pyridin-3-ylmethyloxy) -3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1683]
[1684] TLC: Rf 0.20 (ethyl acetate: methanol = 10: 1);
[1685] _{NMR (CDCl 3): δ 8.75-8.72} (1H, m), 8.70-8.50 (4H, m), 7.96-7.82 (2H, m), 7.46-7.24 (6H, m), 7.05 (1H, d, J = 9.0 Hz), 6.93 (1H, d, J = 9.0 Hz), 5.25 (2H, s), 5.15 (2H, s), 5.01-4.95 (1H, m), 3.81-3.59 (2H, m).
[1686] Example 19
[1687] 3-phenylsulfinyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1688]
[1689] The compound prepared in Example 18 (9) was used in place of the compound prepared in Example 1, and the procedure of Example 2 was repeated to give the compound of the present invention having the following physical data.
[1690] TLC: Rf 0.18 (hexane: AcOEt = 1: 1);
[1691] _{NMR (CDCl 3): δ 2.17} (5 quint, J = 6.0Hz, 2H), 3.08 (dd, J = 14.0, 8.6Hz, 1H), 3.94 (t, J = 6.0Hz, 2H), 3.98 (dd, (D, J = 8.6, 4.8 Hz, 1H), 7.18 (d, J = 7.9 Hz, 1H), 7.35 d, J = 7.9 Hz, 1H), 7.55-7.66 (m, 6H).
[1692] Example 20
[1693] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1694]
[1695] Using the compound prepared in Example 18 instead of the compound prepared in Example 9, the compound of the present invention having the following physical data was obtained by operating in the same manner as in Example 10.
[1696] TLC: Rf 0.67 (ethyl acetate: methanol: 28% ammonia water = 100: 10: 1);
[1697] _{NMR (DMSO-d 6):} δ 8.25 (2H, d, J = 9Hz), 7.78-7.52 (6H, m), 7.52-7.20 (4H, m), 5.74 (1H, d, J = 9Hz), 5.26 (1H, d, J = 15Hz), 4.99 (1H, d, J = 14Hz), 4.19 (1H, d, J = 15Hz).
[1698] Example 20 (1) to 20 (39)
[1699] The compound prepared in Example 18 (1) to 18 (39) was used instead of the compound prepared in Example 18, and the compound was treated in the same manner as in Example 20, or oxone was used instead of 3-chlorobenzoic acid as an oxidizing agent , And if necessary, converted into the corresponding salt by a known method to obtain the following compound of the present invention.
[1700] Example 20 (1)
[1701] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1702]
[1703] TLC: Rf 0.33 (hexane: AcOEt = 1: 1);
[1704] _{NMR (CDCl 3): δ 2.20} (5 quint, J = 6.0Hz, 2H), 3.70 (dd, J = 14.8, 9.3Hz, 1H), 3.99-4.28 (m, 4H), 4.20 (dd, J = 14.8 (M, 2H), 7.52-7.60 (m, 1H), 7.65-7.30 (m, 7.70 (m, 2H).
[1705] Example 20 (2)
[1706] Benzyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1707]
[1708] TLC: Rf 0.39 (hexane: AcOEt = 1: 1);
[1709] _{NMR (CDCl 3): δ 3.73} (dd, J = 15.0, 9.0Hz, 1H), 4.22 (d, J = 15.0Hz, 1H), 4.88 (d, J = 11.7Hz, 1H), 4.99 (d, J (M, 2H), 7.64 (d, J = 7.8Hz, 1H), 7.28-7.58 / RTI &gt; 7.69 (m, 2H).
[1710] Example 20 (3)
[1711] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1712]
[1713] TLC: Rf 0.26 (hexane: AcOEt = 1: 1);
[1714] _{NMR (CDCl 3): δ 1.96} (5 quint, J = 6.1Hz, 2H), 3.57-3.67 (m, 2H), 3.67 (dd, J = 14.9, 9.2Hz, 1H), 3.82-3.92 (m, 1H J = 12.1 Hz, 1H), 3.98-4.09 (m, 1H), 4.21 (dd, J = (d, J = 9.2, 0.5 Hz, 1H), 6.94 (d, J = 8.4 Hz, 1H), 7.22-7.27 (m, 6H), 7.35-7.60 (m, 4H), 7.65-7.69 ).
[1715] Example 20 (4)
[1716] 3-ylmethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1717]
[1718] Free body:
[1719] TLC: Rf 0.17 (ethyl acetate);
[1720] _{NMR (DMSO-d 6):} δ 3.95 (dd, J = 15.0, 8.8Hz, 1H), 4.16 (dd, J = 15.0, 1.2Hz, 1H), 4.93 (d, J = 12.5Hz, 1H), 5.15 (d, J = 8.0 Hz, 1H), 7.35-7.45 (m, 5H), 7.55-7.72 (m, 4H), 7.80 , 1.4 Hz, 1H), 8.56 (dd, J = 5.0, 1.4 Hz, 1H), 8.61 (d, J = 1.4 Hz, 1H).
[1721] Hydrochloride:
[1722] TLC: Rf 0.17 (ethyl acetate);
[1723] _{NMR (DMSO-d 6):} δ 3.98 (dd, J = 15.2, 8.6Hz, 1H), 4.16 (d, J = 15.2Hz, 1H), 5.10 (d, J = 12.8Hz, 1H), 5.29 (d (M, 3H), 7.94 (dd, J = 8.0, 5.4 Hz, 1H), 5.85 (d, J = 8.6 Hz, 1H), 7.38-7.59 1H), 8.38 (d, J = 8.0 Hz, 1H), 8.84 (d, J = 5.4 Hz, 1H), 8.88 (s, 1H).
[1724] Methanesulfonate:
[1725] TLC: Rf 0.31 (ethyl acetate: methanol = 9: 1);
[1726] _{NMR (DMSO-d 6):} δ 2.37 (3H, s), 4.00 (dd, J = 15.0, 8.8Hz, 1H), 4.17 (d- type, J = 15.4Hz, 1H), 5.13 (d, J = J = 8.0 Hz, 1H), 7.39-7.45 (m, 4H), 7.52-7.59 (m, 1H) (D, J = 8.2, 5.8 Hz, 1H), 8.49 (d, J = 8.2 Hz, 1H), 8.89-8.92 (m, 2H), 7.66-7.77 (m, 3H)
[1727] Example 20 (5)
[1728] 2-ylmethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1729]
[1730] TLC: Rf 0.38 (ethyl acetate: methanol: 28% ammonia water = 100: 10: 1);
[1731] _{NMR (CDCl 3): δ 8.77} (1H, d, J = 8Hz), 8.00-7.75 (4H, m), 7.75-7.63 (3H, m), 7.63-7.45 (2H, m), 7.45-7.22 (3H , m), 7.17 (1H, d, J = 8Hz), 5.72-5.25 (3H, m), 4.28 (1H, d, 15Hz), 3.84 (1H, dd, J = 15,9Hz).
[1732] Example 20 (6a)
[1733] 2-ylmethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1734]
[1735] TLC: Rf 0.43 (ethyl acetate: methanol: 28% ammonia water = 100: 10: 1);
[1736] _{NMR (CDCl 3): δ 8.61} (1H, d, J = 4Hz), 7.88-7.18 (10H, m), 7.04 (1H, d, J = 8Hz), 5.37 (1H, d, J = 9Hz), 5.11 (1H, d, J = 15Hz), 4.98 (1H, d, J = 14Hz), 4.24 (1H, d, J = 15Hz).
[1737] Example 20 (6b)
[1738] 2-ylmethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1739]
[1740] TLC: Rf 0.09 (ethyl acetate: methanol: 28% ammonia water = 100: 10: 1);
[1741] _{NMR (CDCl 3 + DMSO-d} 6): δ 8.42-8.22 (1H, m), 7.90-7.20 (11H, m), 5.83 (1H, d, J = 8.5Hz), 5.18 (1H, d, J = 15Hz), 4.93 (1H, d, J = 15Hz), 4.21 (1H, d, J = 15Hz), 4.03 (1H, dd, J = 15, 8.5Hz).
[1742] Example 20 (7)
[1743] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1744]
[1745] Free body:
[1746] TLC: Rf 0.26 (ethyl acetate: methanol: 28% ammonia water = 100: 10: 1);
[1747] _{NMR (CDCl 3 + DMSO-d} 6): δ 8.57 (2H, d, J = 6Hz), 7.80-7.15 (10H, m), 5.75 (1H, d, J = 9Hz), 5.15 (1H, d, J = 14Hz), 4.90 (1H, d, J = 14Hz), 4.19 (1H, d, J = 15Hz), 4.00 (1H, dd, J = 15,9Hz).
[1748] Hydrochloride:
[1749] TLC: Rf 0.31 (ethyl acetate: methanol = 9: 1);
[1750] _{NMR (DMSO-d 6):} δ 8.93 (d, J = 6.5Hz, 2H), 8.00 (d, J = 6.5Hz, 2H), 7.74-7.68 (m, 3H), 7.60-7.54 (m, 1H) , 7.47-7.42 (m, 3H), 7.33 (d, J = 8.0 Hz, 1H), 5.93 (d, J = 9.0 Hz, 1H) J = 16.0 Hz, 1H), 4.19 (d, J = 15.0 Hz, 1H), 4.03 (dd, J = 15.0, 9.0 Hz, 1H).
[1751] Methanesulfonate:
[1752] TLC: Rf 0.31 (ethyl acetate: methanol = 9: 1);
[1753] _{NMR (DMSO-d 6):} δ 8.94 (d, J = 6.3Hz, 2H), 8.03 (d, J = 6.3Hz, 2H), 7.74-7.68 (m, 3H), 7.60-7.55 (m, 1H) , 7.47-7.42 (m, 3H), 7.34 (d, J = 8.0 Hz, 1H), 5.92 (d, J = 9.0 Hz, 1H) J = 16.0 Hz, 1H), 4.19 (d, J = 15.0 Hz, 1H), 4.03 (dd, J = 15.0, 9.0 Hz, 1H), 2.38 (s, 3H).
[1754] Example 20 (8)
[1755] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1756]
[1757] TLC: Rf 0.41 (ethyl acetate: methanol: 28% ammonia water = 100: 10: 1);
[1758] NMR (CDCl ₃ + CD ₃ OD): δ 8.50-8.36 (2H, m), 7.80-7.23 (9H, m), 7.00 , 4.26-3.68 (4H, m), 2.88 (2H, t, J = 7 Hz), 2.20-1.90 (2H, m).
[1759] Example 20 (9)
[1760] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1761]
[1762] TLC: Rf 0.26 (hexane: AcOEt = 1: 1);
[1763] _{NMR (CDCl 3): δ 2.02} (5 quint, J = 5.6Hz, 2H), 2.28 (t, J = 5.6Hz, 1H), 3.71 (dd, J = 14.8, 9.2Hz, 1H), 3.91 (m, J = 5.6 Hz, 2H), 4.05 (dd, J = 14.8,1.0 Hz, 1H), 4.10-4.17 (m, 2H), 5.28 = 8.4 Hz, 1H), 7.23 (d, J = 7.8 Hz, 1H), 7.42-7.62 (m, 4H), 7.66-7.73 (m, 2H).
[1764] Example 20 (10)
[1765] 5-Pentoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide [0154] Benzo [b] thiophene
[1766]
[1767] TLC: Rf 0.40 (hexane: AcOEt = 2: 1);
[1768] _{NMR (CDCl 3): δ 0.96} (t, J = 8Hz, 3H), 1.42 (m, 4H), 1.86 (m, 2H), 3.70 (dd, J = 14, 8Hz, 1H), 3.80 (dd, J (D, J = 8 Hz, 1H), 7.44 (d, J = 2 Hz, 1H) ), 7.46-7.77 (m, 6H).
[1769] Example 20 (11)
[1770] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1771]
[1772] TLC: Rf 0.25 (hexane: AcOEt = 1: 1);
[1773] _{NMR (CDCl 3): δ 3.70} (dd, J = 14, 8Hz, 1H), 3.77 (dd, J = 14, 6Hz, 1H), 4.41 (m, 4H), 5.02 (dd, J = 8, 6Hz, 1H), 7.00 (m, 3H), 7.19 (dd, J = 8, 2Hz, 1H), 7.30-7.77 (m, 9H).
[1774] Example 20 (12)
[1775] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1776]
[1777] TLC: Rf 0.15 (hexane: AcOEt = 1: 1);
[1778] _{NMR (CDCl 3): δ 2.11} (m, 2H), 3.65 (dd, J = 14, 8Hz, 1H), 3.78 (dd, J = 14, 5Hz, 1H), 3.89 (m, 2H), 4.25 (m , 2H), 5.01 (dd, J = 8, 5 Hz, 1H), 7.12 (dd, J = 9,2Hz, 1H), 7.45-7.77 (m, 7H).
[1779] Example 20 (13)
[1780] 3-ylmethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1781]
[1782] Free body:
[1783] TLC: Rf 0.30 (ethyl acetate);
[1784] _{NMR (DMSO-d 6):} δ 3.79 (dd, J = 15.1, 3.2Hz, 1H), 4.00 (dd, J = 15.1, 9.4Hz, 1H), 5.27 (s, 2H), 5.74 (dd, J = 7.7 (dd, J = 7.8, 4.9 Hz, 1H), 7.57 (dd, J = 8.7, 2.2 Hz, 1H) J = 7.8, 2.0 Hz, 1H), 8.58 (dd, J = 4.9, 2.0 Hz, 1H), 8.71 (d, J = 2.0 Hz, 1H).
[1785] Hydrochloride:
[1786] TLC: Rf 0.65 (ethyl acetate: triethylamine = 10: 1);
[1787] _{NMR (DMSO-d 6):} δ 3.77 (dd, J = 15.0, 3.4Hz, 1H), 3.99 (dd, J = 15.0, 9.6Hz, 1H), 5.43 (s, 2H), 5.77 (dd, J = 2H), 7.74-7.82 (m, 4H), 7.41 (dd, J = 8.8, 2.2Hz, 1H) ), 8.02 (dd, J = 8.4, 5.6 Hz, 1H), 8.57 (d-form, J = 8.4 Hz, 1H), 8.88 1H).
[1788] Methanesulfonate:
[1789] TLC: Rf 0.30 (ethyl acetate);
[1790] _{NMR (DMSO-d 6):} δ 2.37 (3H, s), 3.77 (dd, J = 15.0, 3.3Hz, 1H), 4.00 (dd, J = 15.0, 9.3Hz, 1H), 5.77 (dd, J = (D, J = 8.7, 2.2 Hz, 1H), 7.59-7.66 (m, 2H), 7.74-7.83 (m, 4H J = 8.0 Hz, 1H), 8.06 (dd, J = 8.0, 5.6 Hz, 1H), 8.61 1.6 Hz, 1H).
[1791] Example 20 (14)
[1792] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene hydrochloride
[1793]
[1794] TLC: Rf 0.32 (ethyl acetate: methanol = 10: 1);
[1795] _{NMR (CD 3 OD): δ} 8.80 (1H, s), 8.71 (1H, d, J = 6Hz), 8.56 (1H, d, J = 8Hz), 8.02 (1H, t, J = 7Hz), 7.85- (2H, t, J = 6 Hz), 3.98-3.65 (2H, s), 7.42 (6H, m), 7.27 , m), 3.10 (2H, t, J = 7 Hz), 2.40-2.10 (2H, m).
[1796] Example 20 (15)
[1797] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1798]
[1799] TLC: Rf 0.43 (hexane: AcOEt = 1: 1);
[1800] _{NMR (CDCl 3): δ 2.29} (5 quint, J = 6.0Hz, 2H), 3.65-3.81 (m, 2H), 4.15 (t, J = 6.0Hz, 2H), 4.21 (t, J = 6.0Hz, 2H), 4.99 (dd, J = 7.3, 5.9 Hz, 1H), 6.89-6.99 (m, 3H), 7.08 (d, J = 2.2 Hz, 1H), 7.23 ), 7.25-7.33 (m, 2H), 7.45-7.52 (m, 2H), 7.62-7.70 (m, 3H), 7.85 (d, J = 8.8 Hz, 1H).
[1801] Example 20 (16)
[1802] Benzyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1803]
[1804] TLC: Rf 0.50 (hexane: AcOEt = 1: 1);
[1805] _{NMR (CDCl 3): δ 3.71} (dd, J = 14.7, 7.7Hz, 1H), 3.80 (dd, J = 14.7, 5.5Hz, 1H), 5.00 (dd, J = 7.7, 5.5Hz, 1H), 5.10 (s, 2H), 7.15 (d, J = 2.5 Hz, 1H), 7.30 (dd, J = 8.5, 2.5 Hz, 1H), 7.40-7.53 (m, 7H), 7.63-7.71 7.87 (d, J = 8.5 Hz, 1 H).
[1806] Example 20 (17)
[1807] 6-pentoxy-3-phenylsulfonyl-2,3-dihydro-1, 1-dioxide [
[1808]
[1809] TLC: Rf 0.26 (hexane: AcOEt = 2: 1);
[1810] _{NMR (CDCl 3): δ 0.94} (t, J = 6.4Hz, 3H), 1.42 (m, 4H), 1.81 (m, 2H), 3.70 (dd, J = 14.9, 7.6Hz, 1H), 3.79 (dd (D, J = 7.6 Hz, 1H), 7.04 (d, J = 2.4 Hz, 1H), 7.23 (dd, J = 8.8, 2.4 Hz, 1H), 7.46-7.54 (m, 2H), 7.64-7.72 (m, 3H), 7.84 (d, J = 8.8 Hz, 1H).
[1811] Example 20 (18)
[1812] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1813]
[1814] Free body:
[1815] TLC: Rf 0.27 (hexane: ethyl acetate: triethylamine = 2: 4: 1);
[1816] _{NMR (CDCl 3): δ 2.56} (t, J = 4.5Hz, 4H), 2.81 (t, J = 5.6Hz, 2H), 3.70-3.77 (m, 6H), 4.14 (t, J = 5.6Hz, 2H ), 5.01 (dd, J = 7.5, 5.7 Hz, 1H), 7.08 (d, J = 2.3 Hz, 1H), 7.25 (dd, J = 8.7, 2.3 Hz, 1H), 7.47-7.54 , 7.64-7.72 (m, 3H), 7.83 (d, J = 8.7 Hz, 1H).
[1817] Hydrochloride:
[1818] TLC: Rf 0.27 (hexane: ethyl acetate: triethylamine = 4: 8: 1);
[1819] _{NMR (CD 3 OD): δ} 3.43-3.53 (m, 4H), 3.68 (t, J = 4.8Hz, 2H), 3.80 (dd, J = 15.4, 8.4Hz, 1H), 3.95 (dd, J = 15.4 , 4.0 Hz, 1H), 3.92-4.02 (m, 4H), 4.51 (t, J = 4.8 Hz, 2H), 5.45 (dd, J = 8.4, 4.0 Hz, 1H) , 7.42 (dd, J = 8.8, 2.6 Hz, 1H), 7.55-7.63 (m, 2H), 7.71-7.81 (m, 4H).
[1820] Example 20 (19)
[1821] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1822]
[1823] TLC: Rf 0.22 (hexane: AcOEt = 1: 2);
[1824] _{NMR (CDCl 3): δ 2.06} (5 quint, J = 6.0Hz, 2H), 3.71 (dd, J = 14.6, 7.5Hz, 1H), 3.79 (dd, J = 14.6, 5.6Hz, 1H), 3.85 ( J = 6.0 Hz, 2H), 4.16 (t, J = 6.0 Hz, 2H), 5.00 (dd, J = 7.5, 5.6 Hz, 1H), 7.08 dd, J = 8.8, 2.4 Hz, 1H), 7.47-7.55 (m, 2H), 7.64-7.71 (m, 3H), 7.84 (d, J = 8.8 Hz, 1H).
[1825] Example 20 (20)
[1826] 6-Pyridin-3-ylmethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1827]
[1828] Free body:
[1829] TLC: Rf 0.39 (ethyl acetate);
[1830] _{NMR (DMSO-d 6):} δ 3.78 (dd, J = 15.2, 3.1Hz, 1H), 4.01 (dd, J = 15.2, 9.2Hz, 1H), 5.29 (s, 2H), 5.69 (dd, J = J = 8.0, 1.0 Hz, 1 H), 8.57 (m, 3H), 7.42-7.47 (m, 3H), 7.58-7.66 (dd, J = 4.8, 1.6 Hz, 1H), 8.69 (d, J = 1.6 Hz, 1H).
[1831] Hydrochloride:
[1832] TLC: Rf 0.39 (ethyl acetate);
[1833] _{NMR (DMSO-d 6):} δ 3.78 (dd, J = 15.2, 3.0Hz, 1H), 4.01 (dd, J = 15.2, 9.4Hz, 1H), 5.72 (dd, J = 9.4, 3.0Hz, 1H) , 7.46-7.51 (m, 2H), 7.59-7.66 (m, 3H), 7.75-7.83 (m, 3H), 7.99 (dd, J = 8.0,5.4Hz, 1H) , 8.87 (dd, J = 5.4, 1.2 Hz, 1H), 8.99 (d, J = 1.2 Hz, 1H).
[1834] Example 20 (21)
[1835] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1836]
[1837] TLC: Rf 0.55 (hexane: AcOEt = 1: 2);
[1838] _{NMR (DMSO-d 6):} δ 8.36-8.34 (m, 1H), 8.25-8.20 (m, 1H), 7.93 (d- type, J = 7.6Hz, 1H), 7.82-7.72 (m, 4H), 2H), 5.70 (dd, J = 9.4, 3.0 Hz, 1H), 5.40 (s, 2H), 4.02 (dd, J = 15.2, 9.4 Hz, 1H), 3.79 (dd, J = 15.2, 3.0 Hz, 1 H).
[1839] Example 20 (22)
[1840] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxo [b] thiophene
[1841]
[1842] TLC: Rf 0.60 (hexane: AcOEt = 1: 1);
[1843] _{NMR (CDCl 3): δ 2.35} (m, 2H), 3.60 (t, J = 6.0Hz, 2H), 3.70-3.91 (m, 2H), 4.17 (t, J = 6.0Hz, 2H), 5.01 (dd 2H), 7.67 (m, 3H), 7.89 (m, 1H), 7.09 (d, J = 3.0 Hz, 1H), 7.25 (m,
[1844] Example 20 (23)
[1845] 3-phenylsulfonyl-2, 3-dihydro-1, 1-dioxo [b] thiophene
[1846]
[1847] TLC: Rf 0.48 (hexane: AcOEt = 1: 1);
[1848] _{NMR (CDCl 3): δ 7.70-7.43} (7H, m), 6.99 (1H, d, J = 8.2Hz), 5.01 (1H, dd, J = 8.6, 5.4Hz), 4.07 (2H, t, J = 6.8 Hz), 3.73-3.68 (2H, m), 1.80 (2H, pentane, J = 6.8 Hz), 1.50-1.20 (4H, m), 0.89 (3H, t, J = 6.8 Hz).
[1849] Example 20 (24)
[1850] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1851]
[1852] TLC: Rf 0.27 (hexane: AcOEt = 1: 1);
[1853] _{NMR (CDCl 3): δ 7.70-6.88} (13H, m), 5.01 (1H, dd, J = 8.1, 5.4Hz), 4.50-4.40 (2H, m), 4.40-4.31 (2H, m), 3.76- 3.70 (2 H, m).
[1854] Example 20 (25)
[1855] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1856]
[1857] TLC: Rf 0.46 (ethyl acetate);
[1858] _{NMR (CDCl 3): δ 7.75-7.40} (7H, m), 7.07 (1H, d, J = 8.0Hz), 5.05 (1H, dd, J = 8.4, 5.4Hz), 4.26 (2H, t, J = 5.8 Hz), 3.85-3.65 (4H, m), 2.03 (2H, quintet, J = 5.8 Hz).
[1859] Example 20 (26a)
[1860] 3-ylmethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene hydrochloride
[1861]
[1862] TLC: Rf 0.30 (ethyl acetate: triethylamine = 20: 1);
[1863] _{NMR (DMSO-d 6):} δ 8.85-8.75 (2H, m), 8.27 (1H, d, J = 7.6Hz), 7.92-7.55 (7H, m), 7.43 (1H, d, J = 8.2Hz) , 7.26 (1H, d, J = 7.6 Hz), 5.80 (1H, dd, J = 9.4, 3.2 Hz), 5.51 (2H, s), 3.99 1H, dd, J = 15.3, 3.2 Hz).
[1864] Example 20 (26b)
[1865] 3-ylmethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1866]
[1867] TLC: Rf 0.26 (ethyl acetate: methanol: triethylamine = 16: 3: 1);
[1868] _{NMR (DMSO-d 6):} δ 8.38 (1H, s), 8.30 (1H, d, J = 5.4Hz), 7.90-7.42 (8H, m), 7.39 (1H, d, J = 7.8Hz), 7.23 (1H, d, J = 7.8 Hz), 5.78 (1H, dd, J = 9.7, 3.4 Hz), 5.39 (2H, s), 3.99 78 (1H, dd, J = 15, 3.4 Hz).
[1869] Example 20 (27)
[1870] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1871]
[1872] TLC: Rf 0.28 (hexane: AcOEt = 1: 1);
[1873] _{NMR (CDCl 3): δ 1.48} (s, 9H), 3.76 (dd, J = 14.9, 9.2Hz, 1H), 4.16 (d, J = 16.0Hz, 1H), 4.25 (dd, J = 1.9, 1.2Hz J = 8.1, 0.7 Hz, 1H), 7.35 (d, J = 9.1 Hz, 1H), 4.31 (d, J = 16.0 Hz, 7.4 Hz, 1H), 7.44-7.57 (m, 3H), 7.59-7.67 (m, 1H), 7.78-7.83 (m, 2H).
[1874] Example 20 (28)
[1875] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1876]
[1877] TLC: Rf 0.50 (hexane: AcOEt = 1: 1);
[1878] _{NMR (CDCl 3): δ 1.53} (s, 9H), 3.74 (d- type, J = 6Hz, 2H), 4.67 (m, 2H), 5.00 (t, J = 6Hz, 1H), 7.17 (dd, J = 7.52 (m, 2H), 7.55 (d, J = 8 Hz, 1H), 7.66 (m, 3H).
[1879] Example 20 (29)
[1880] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1881]
[1882] TLC: Rf 0.42 (hexane: AcOEt = 1: 1);
[1883] _{NMR (CDCl 3): δ 1.48} (s, 3H), 3.67-3.83 (m, 2H), 4.56 (s, 2H), 5.00 (dd, J = 7.4, 5.6Hz, 1H), 6.99 (d, J = 1H), 7.29 (dd, J = 8.8,2.6Hz, 1H), 7.46-7.53 (m, 2H), 7.61-7.70 (m, 3H), 7.89 (d, J = 8.8Hz, 1H).
[1884] Example 20 (30)
[1885] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1886]
[1887] TLC: Rf 0.28 (hexane: AcOEt = 1: 1);
[1888] NMR (CDCl ₃ ): 隆 7.70-7.47 (7H, m), 6.91-6.86 (1H, m), 5.02 (1H, dd, J = 8.3,5.6Hz) 2H, m), 1.44 (9H, s).
[1889] Example 20 (31)
[1890] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1891]
[1892] TLC: Rf 0.35 (hexane: AcOEt = 1: 2);
[1893] _{NMR (CDCl 3): δ 3.42-3.56} (m, 1H), 3.63-3.76 (m, 1H), 3.73 (dd, J = 15.2, 9.6Hz, 1H), 4.02-4.34 (m, 2H), 4.10 ( (d, J = 15.2, 1.2 Hz, 1H), 5.29 (dd, J = 9.6, 1.2 Hz, 1H), 5.78 , J = 7.5 Hz, 1H), 7.40-7.64 (m, 4H), 7.21-7.76 (m, 2H).
[1894] Example 20 (32)
[1895] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1896]
[1897] TLC: Rf 0.30 (hexane: AcOEt = 1: 2);
[1898] _{NMR (CDCl 3): δ 1.41} (s, 9H), 1.93 (m, 2H), 3.35 (m, 2H), 3.72 (dd, J = 15.0, 9.0Hz, 1H), 3.99 (t, J = 6.1Hz J = 9.0 Hz, 1 H), 7.02 (d, J = 7.5 Hz, 1 H), 7.25 (d, , J = 7.5 Hz, 1H), 7.43-7.67 (m, 4H), 7.70-7.75 (m, 2H).
[1899] Example 20 (33)
[1900] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1901]
[1902] TLC: Rf 0.40 (hexane: AcOEt = 1: 1);
[1903] _{NMR (CDCl 3): δ 1.47} (s, 9H), 3.54 (m, 2H), 3.66 (dd, J = 15, 8Hz, 1H), 3.80 (dd, J = 15, 5Hz, 1H), 4.13 (t (D, J = 8 Hz, 2H), 5.00 (dd, J = 8 Hz, 1H), 5.00 ), 7.55 (m, 3H), 7.72 (m, 3H).
[1904] Example 20 (34)
[1905] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene A solution of 6- (3- (t-butoxycarbonylamino)
[1906]
[1907] TLC: Rf 0.41 (hexane: AcOEt = 1: 2);
[1908] _{NMR (CDCl 3): δ 1.44} (s, 9H), 2.01 (5 quint, J = 6.2Hz, 2H), 3.32 (q, J = 6.2Hz, 2H), 3.71 (dd, J = 14.6, 7.7Hz, 1H), 3.79 (dd, J = 14.6,5.5 Hz, 1H), 4.06 (t, J = 6.2 Hz, 2H), 4.68 J = 8.8, 2.4 Hz, 1H), 7.47-7.54 (m, 2H), 7.64-7.72 (m, 3H), 7.85 (d, J = 8.8 Hz, 1H).
[1909] Example 20 (35)
[1910] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1911]
[1912] TLC: Rf 0.24 (hexane: AcOEt = 1: 1);
[1913] NMR (CDCl ₃ ): δ 1.46 (s, 9H), 3.56 (q, J = 5.4 Hz, 2H), 3.71 (dd, J = 14.8, 7.7 Hz, 1H) (D, J = 7.7, 5.6 Hz, 1H), 7.05 (d, J = 2.6 Hz, 1H), 7.24 (dd, J = 8.8, 2.6 Hz, 1H), 7.47-7.55 (m, 2H), 7.65-7.72 (m, 3H), 7.88 (d, J = 8.8 Hz, 1H).
[1914] Example 20 (36)
[1915] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1916]
[1917] TLC: Rf 0.36 (hexane: AcOEt = 2: 1);
[1918] _{NMR (CDCl 3): δ 7.72-7.40} (7H, m), 7.04 (1H, d, J = 8.2Hz), 5.22 (1H, bs), 5.02 (1H, dd, J = 8.7, 5.0Hz), 4.25 -4.10 (2H, m), 3.85-3.65 (2H, m), 3.60-3.46 (2H, m), 1.42 (9H, s).
[1919] Example 20 (37)
[1920] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1921]
[1922] TLC: Rf 0.19 (hexane: AcOEt = 1: 1);
[1923] _{NMR (CDCl 3): δ 7.80-7.38} (6H, m), 7.23 (1H, d, J = 8Hz), 7.05 (1H, d, J = 8Hz), 5.23 (1H, d, J = 9Hz), 4.70 (1H, m), 4.05 (1H, m), 4.08 (1H, d, J = 15Hz), 3.95-3.60 2.15-1.58 (4 H, m), 1.48 (9 H, s).
[1924] Example 20 (38)
[1925] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene (4-hydroxyphenyl)
[1926]
[1927] TLC: Rf 0.25 (hexane: AcOEt = 1: 3);
[1928] _{NMR (CDCl 3): δ 7.77} (2H, d, J = 8.2Hz), 7.70-7.55 (1H, m), 7.55-7.40 (2H, m), 6.95 (2H, s), 5.71 (1H, brs) , 5.40-5.15 (2H, m), 4.20-3.30 (10H, m), 1.43 (18H, s).
[1929] Example 20 (39)
[1930] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1931]
[1932] TLC: Rf 0.13 (hexane: AcOEt = 1: 1);
[1933] _{NMR (CDCl 3 + CD 3 OD} ): δ 8.35 (1H, s), 8.27 (1H, d, J = 8Hz), 7.87 (1H, d, J = 8Hz), 7.80-7.50 (5H, m), 7.50 (2H, m), 4.11 (1H, dd, J = 15Hz), 7.25-7.25 (3H, m), 7.13 , 1 Hz), 3.76 (1H, dd, J = 15, 9 Hz).
[1934] Example 21
[1935] 4-carboxymethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1936]
[1937] Trifluoroacetic acid (5 ml) was added to a dichloromethane (5 ml) solution of the compound (105 mg) prepared in Example 20 (27) at 0 deg. The reaction mixture was stirred at room temperature for 1 hour. The reaction mixture was concentrated. The residue was recrystallized from diethyl ether to give the compound (63 mg) of the present invention having the following physical data.
[1938] TLC: Rf 0.20 (CHCl 3: MeOH = 4: 1);
[1939] NMR (CDCl ₃ + CD ₃ OD): 3.79 (dd, J = 14.9, 9.0 Hz, 1H), 4.23 (dd, J = , 4.43 (d, J = 16.1 Hz, 1H), 5.45 (dd, J = 9.0,0.0 Hz, 1H) , 7.45-7.59 (m, 3H), 7.62-7.70 (m, 1H), 7.77-7.81 (m, 2H).
[1940] Examples 21 (1) to 21 (3)
[1941] The compound of the present invention shown below was obtained by following the procedure of Example 21 while using the compound prepared in Example 20 (28) - 20 (30) instead of the compound prepared in Example 20 (27) .
[1942] Example 21 (1)
[1943] 5-carboxymethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1944]
[1945] TLC: Rf 0.30 (CHCl 3: MeOH = 4: 1);
[1946] _{NMR (CDCl 3 + CD 3 OD} ): δ 3.79 (d- type, J = 6Hz, 2H), 4.76 (s, 2H), 5.10 (t, J = 6Hz, 1H), 7.20 (dd, J = 8, (D, J = 8 Hz, 1 H), 7.55 (m, 2H), 7.69 (m, 3H).
[1947] Example 21 (2)
[1948] 6-carboxymethoxy-3-phenylsulfonyl-2,3-dihydro-1, 1-dioxide [
[1949]
[1950] TLC: Rf 0.25 (CHCl 3: MeOH = 4: 1);
[1951] _{NMR (CDCl 3 + CD 3 OD} ): δ 3.70-3.85 (m, 2H), 4.68 (s, 2H), 5.07 (t- type, J = 6.6Hz, 1H), 7.07 (d, J = 2.5Hz, 1H), 7.32 (dd, J = 8.8,2.5 Hz, 1H), 7.47-7.55 (m, 2H), 7.63-7.73 (m, 3H), 7.83 (d, J = 8.8 Hz, 1H).
[1952] Example 21 (3)
[1953] 7-carboxymethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1954]
[1955] TLC: Rf 0.29 (ethyl acetate: acetic acid = 10: 1);
[1956] _{NMR (CDCl 3 + DMSO-d} 6): δ 7.52-7.26 (6H, m), 7.20 (1H, d, J = 7.8Hz), 6.77 (1H, d, J = 8.2Hz), 4.98 (1H, dd , J = 7.8, 5.6 Hz), 4.52 (2H, s), 3.58-3.54 (2H, m).
[1957] Example 22
[1958] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1959]
[1960] The thionyl chloride (10 ml) suspension of the compound (480 mg) prepared in Example 21 was refluxed for 15 minutes. The thionyl chloride was distilled off and the residue was dissolved in methylene chloride (5 ml). To the solution was added methylene chloride (10 ml) of 3- (aminomethyl) pyridine (0.15 ml) and triethylamine (1 ml) Under ice-cooling. The reaction mixture was stirred at room temperature for 2 hours. Water was added to the reaction mixture and extracted with ethyl acetate. The extract was washed successively with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and concentrated. The residue was purified by silica gel column chromatography (ethyl acetate: triethylamine = 100: 1) to obtain the compound (421 mg) of the present invention having the following physical data.
[1961] Free body:
[1962] TLC: Rf 0.49 (ethyl acetate: methanol: triethylamine = 8: 1: 1);
[1963] _{NMR (DMSO-d 6):} δ 4.03 (dd, J = 14.9, 8.4Hz, 1H), 4.11 (d, J = 14.5Hz, 1H), 4.12 (dd, J = 14.9, 1.6Hz, 1H), 4.33 (dd, J = 15.3, 6.0 Hz, 1H), 4.44 (dd, J = 15.3, 6.0 Hz, 1H), 4.57 (d, J = 14.5 Hz, 1H) J = 8.0 Hz, 1H), 7.49-7.54 (m, 2H), 7.34 (dd, J = 8.0, 4.7 Hz, J = 7.7 Hz, 1H), 7.63-7.73 (m, 5H), 8.39 (t, J = 6.0 Hz, 1H), 8.46 (dd, J = 4.7,
[1964] Hydrochloride:
[1965] TLC: Rf 0.49 (ethyl acetate: methanol: triethylamine = 8: 1: 1);
[1966] _{NMR (DMSO-d 6):} δ 4.04 (dd, J = 15.0, 8.7Hz, 1H), 4.12 (d, J = 14.7Hz, 1H), 4.13 (dd, J = 15.0, 1.5Hz, 1H), 4.49 (dd, J = 15.8, 6.2 Hz, 1H), 4.57 (dd, J = 15.8, 6.2 Hz, 1H), 4.60 J = 7.6 Hz, 1H), 7.52-7.57 (m, 2H), 7.64 (d, J = 8.2 Hz, 1H), 7.68 (d, J = 8.0 Hz, 1H), 8.78 (t, J = 6.2 Hz, 1H), 8.78 (d, J = = 5.4 Hz, 1 H), 8.81 (s 1H).
[1967] Example 22 (1) and 22 (2)
[1968] The procedure of Example 22 was repeated except that 3- (aminomethyl) pyridine was used instead of 3- (aminomethyl) pyridine, and if necessary, the compound of the present invention .
[1969] Example 22 (1)
[1970] Carbonylmethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[1971]
[1972] Free body:
[1973] TLC: Rf 0.29 (ethyl acetate: methanol: triethylamine = 8: 1: 1);
[1974] _{NMR (CDCl 3): δ 2.24} (s, 6H), 2.51 (t- type, J = 6.0Hz, 2H), 3.49 (m, J = 6.0Hz, 2H), 3.77 (dd, J = 15.3, 9.6Hz J = 14.2 Hz, 1H), 4.39 (d, J = 15.3, 1.3 Hz, 1H) J = 8.0 Hz, 1 H), 7.42-7.48 (m, 2H), 7.57 (t, J = 8.0 Hz, , 7.59-7.65 (m, IH), 7.70-7.74 (m, 2H), 7.94 (br, IH).
[1975] Hydrochloride:
[1976] TLC: Rf 0.29 (ethyl acetate: methanol: triethylamine = 8: 1: 1);
[1977] _{NMR (DMSO-d 6):} δ 2.76 (s, 6H), 3.14-3.18 (m, 2H), 3.44-3.56 (m, 2H), 4.00 (dd, J = 15.0, 9.3Hz, 1H), 4.03 ( (d, J = 14.4 Hz, 1H), 4.17 (d, J = 15.0 Hz, 1H), 4.50 J = 8.0 Hz, 1H), 7.39 (d, J = 8.0 Hz, 1H), 7.56-7.62 (m, 2H), 7.64 ), 8.23 (t, J = 5.5 Hz, 1 H).
[1978] Example 22 (2)
[1979] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene-2- ] Thiophene
[1980]
[1981] TLC: Rf 0.52 (ethyl acetate: methanol: triethylamine = 9: 1: 1);
[1982] _{NMR (CDCl 3): δ 2.22} (s, 3H), 2.29 (s, 3H), 2.44-2.55 (m, 2H), 3.29-3.35 (m, 1H), 3.56-3.60 (m, 1H), 3.73- (S, 1H), 4.76 (d, J = 15.0 Hz, 0.5H), 4.88 (s, J = 15.0 Hz, 0.5H), 7.10-7.36 (m, 6H), 7.41-7.53 (m, 4H) ), 7.61-7.68 (m, 3H).
[1983] Example 23
[1984] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene hydrochloride
[1985]
[1986] The compound prepared in Example 20 (31) was used in place of the compound prepared in Example 6 (8) to give the compound of the present invention having the following physical data.
[1987] TLC: Rf 0.21 (ethyl acetate: methanol: triethylamine = 8: 2: 1);
[1988] _{NMR (DMSO-d 6):} δ 2.66-2.78 (m, 1H), 3.02-3.12 (m, 1H), 3.83-4.18 (m, 4H), 6.23 (d- type, J = 6.6Hz, 1H), 7.27 (d, J = 8.0 Hz, 1H), 7.39 (d, J = 7.6 Hz, 1H), 7.58-7.68 (m, 3H), 7.72-7.79 (m, 3H), 8.02 (br, 2H).
[1989] Example 23 (1) to 23 (7)
[1990] The compound of the present invention shown below was obtained by following the procedure of Example 23 while using the compound prepared in Example 20 (32) to 20 (38) instead of the compound prepared in Example 20 (31) .
[1991] Example 23 (1)
[1992] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene hydrochloride
[1993]
[1994] TLC: Rf 0.12 (ethyl acetate: methanol: triethylamine = 8: 4: 1);
[1995] _{NMR (DMSO-d 6):} δ 1.85-1.93 (m, 2H), 2.93 (q, J = 6.4Hz, 2H), 3.87-4.08 (m, 2H), 3.97 (dd, J = 15.0, 8.4Hz, J = 7.8 Hz, 1H), 7.33 (d, J = 7.8 Hz, 1H) Hz, 1 H), 7.59-7.78 (m, 6 H), 8.15 (br, 3 H).
[1996] Example 23 (2)
[1997] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene hydrochloride
[1998]
[1999] TLC: Rf 0.25 (ethyl acetate: methanol: triethylamine = 8: 2: 1);
[2000] _{NMR (DMSO-d 6):} δ 7.81-7.72 (m, 4H), 7.66-7.59 (m, 2H), 7.32-7.27 (m, 2H), 5.77 (dd, J = 9, 3.5Hz, 1H), J = 15, 3.5 Hz, 1H), 3.38-3.32 (m, 2H), 4.27 (m, 2H), 3.94 (dd, J = 15,9Hz, 1H).
[2001] Example 23 (3)
[2002] 6- (3-aminopropyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene hydrochloride
[2003]
[2004] TLC: Rf 0.40 (ethyl acetate: methanol: triethylamine = 8: 2: 1);
[2005] _{NMR (DMSO-d 6):} δ 2.05 (5 quint, J = 6.8Hz, 2H), 2.95 (t, J = 6.8Hz, 2H), 3.76 (dd, J = 15.2, 3.0Hz, 1H), 4.00 ( 2H), 5.70 (dd, J = 9.4, 3.0 Hz, 1H), 7.29-7.38 (m, 2H), 7.56-7.67 (m, 3H), 7.76-7.79 (m, 3H), 8.08 (br, 2H).
[2006] Example 23 (4)
[2007] 6- (2-aminoethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene hydrochloride
[2008]
[2009] TLC: Rf 0.16 (ethyl acetate: methanol: triethylamine = 9: 1: 1);
[2010] _{NMR (DMSO-d 6):} δ 3.22 (t, J = 4.9Hz, 2H), 3.79 (dd, J = 15.1, 3.0Hz, 1H), 4.01 (dd, J = 15.1, 9.4Hz, 1H), 4.32 (t, J = 4.9 Hz, 2H), 5.73 (dd, J = 9.4, 3.0 Hz, 1H), 7.35 , 7.62 (d, J = 8.8 Hz, 1H), 7.64-7.66 (m, 2H), 7.76-7.81 (m, 3H), 8.35 (br, 3H).
[2011] Example 23 (5)
[2012] 7- (2-aminoethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene hydrochloride
[2013]
[2014] TLC: Rf 0.38 (ethyl acetate: acetic acid: water = 3: 1: 1);
[2015] _{NMR (DMSO-d 6):} δ 8.18 (3H, brs), 7.83-7.60 (6H, m), 7.40 (1H, d, J = 8Hz), 7.22 (1H, d, J = 8Hz), 5.81 (1H dd, J = 9.6, 3.2 Hz), 4.44-3.30 (2H, m), 3.96 (1H, dd, J = 15, 9.6 Hz), 3.76 2H, t, J = 6 Hz).
[2016] Example 23 (6)
[2017] 4-yl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene hydrochloride
[2018]
[2019] TLC: Rf 0.47 (ethyl acetate: acetic acid: water = 3: 1: 1);
[2020] _{NMR (DMSO-d 6):} δ 8.91 (2H, brs), 7.90-7.52 (6H, m), 7.41 (1H, d, J = 8Hz), 7.33 (1H, d, J = 8Hz), 5.71 (1H (d, J = 7 Hz), 4.95-4.70 (1H, m), 4.20-3.80 (2H, m), 3.50-2.95 (4H, m), 2.30-1.60 (4H, m).
[2021] Example 23 (7)
[2022] 4,7-bis [(2-aminoethyl) oxy] -3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene dihydrochloride
[2023]
[2024] TLC: Rf 0.22 (ethyl acetate: methanol: triethylamine = 4: 1: 1);
[2025] _{NMR (DMSO-d 6):} δ 8.10 (6H, brs), 7.85-7.70 (3H, m), 7.70-7.50 (2H, m), 7.37 (1H, d, J = 8.6Hz), 7.23 (1H, (2H, m), 4.15-3.90 (4H, m), 3.85-3.65 (1H, m), 3.25-3.15 (2 H, m), 3.15 - 2.90 (1 H, m).
[2026] Example 24
[2027] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2028]
[2029] Using the compound prepared in Example 23 instead of the compound prepared in Example 7, the compound of the present invention having the following physical data was obtained by operating in the same manner as in Example 8.
[2030] Free body:
[2031] TLC: Rf 0.47 (ethyl acetate: methanol: triethylamine = 8: 2: 1);
[2032] _{NMR (CDCl 3): δ 2.33} (s, 6H), 2.52-2.77 (m, 2H), 3.72 (dd, J = 15.0, 9.4Hz, 1H), 3.79-3.89 (m, 1H), 4.00-4.12 ( J = 8.8 Hz, 1H), 6.99 (d, J = 8.2 Hz, 1H), 7.28 (d, J = 7.2 Hz, 1H), 7.43-7.66 (m, 4H), 7.72-7.77 (m, 2H).
[2033] Hydrochloride:
[2034] TLC: Rf 0.47 (ethyl acetate: methanol: triethylamine = 8: 2: 1);
[2035] _{NMR (CD 3 OD): δ} 3.05 (s, 6H), 3.52-3.76 (m, 2H), 3.83-3.99 (m, 2H), 4.38-4.63 (m, 2H), 5.89 (t, J = 5.4Hz , 7.30 (d, J = 7.7 Hz, 1H), 7.39 (d, J = 7.7 Hz, 1H), 7.51-7.59 (m, 2H), 7.66-7.78 (m, 4H).
[2036] Example 24 (1) to 24 (5)
[2037] The procedure of Example 14 was repeated using the compound prepared in Example 23 (1) - (5) instead of the compound prepared in Example 23, and, if necessary, To give the corresponding compound of the present invention as shown below. However, when the compounds of Example 23 (1) and Example 23 (3) were used, the compounds of Example 24 (1b) and Example 24 (3b) were also produced.
[2038] Example 24 (1a)
[2039] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2040]
[2041] Free body:
[2042] TLC: Rf 0.35 (ethyl acetate: methanol: triethylamine = 8: 2: 1);
[2043] _{NMR (CDCl 3): δ 1.86} (5 quint, J = 7.0Hz, 2H), 2.26 (s, 6H), 2.47 (t, J = 7.0Hz, 2H), 3.74 (dd, J = 15.0, 9.2Hz, J = 8.8 Hz, 1H), 6.99 (d, J = 7.8 Hz, 1H), 3.83-4.03 (m, 2H), 4.21 (dd, J = ), 7.24 (d, J = 7.8 Hz, 1 H), 7.48-7.74 (m, 6H).
[2044] Hydrochloride:
[2045] TLC: Rf 0.35 (ethyl acetate: methanol: triethylamine = 8: 2: 1);
[2046] _{NMR (DMSO-d 6):} δ 2.15 (m, 2H), 2.80 (s, 6H), 3.31 (t, J = 7.5Hz, 2H), 3.75 (dd, J = 15.2, 9.2Hz, 1H), 4.15 (d, J = 9.2, 1.1 Hz, 1H), 7.32-7.39 (m, 2H), 7.55 (d, J = 7.72 (m, 3 H), 7.80 - 7.85 (m, 3 H).
[2047] Example 24 (1b)
[2048] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2049]
[2050] TLC: Rf 0.36 (ethyl acetate: triethylamine = 9: 1);
[2051] _{NMR (CDCl 3): δ 1.88} (5 quint, J = 6.6Hz, 2H), 2.38 (s, 3H), 2.69 (m, 2H), 3.51 (d, J = 17.0Hz, 1H), 3.61 (d, J = 17.0 Hz, 1H), 3.73 (dd, J = 15.0, 9.4 Hz, 1H), 3.96 (m, 2H), 4.13 (dd, J = = 8.4 Hz, 1H), 7.00 (d, J = 7.8 Hz, 1H), 7.24 (d, J = 7.8 Hz, 1H), 7.42-7.74 (m, 6H).
[2052] Example 24 (2)
[2053] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2054]
[2055] Free body:
[2056] TLC: Rf 0.55 (ethyl acetate: methanol: triethylamine = 8: 2: 1);
[2057] _{NMR (DMSO-d 6):} δ 2.23 (s, 6H), 2.66 (t, J = 6Hz, 2H), 3.77 (dd, J = 15, 3Hz, 1H), 3.98 (dd, J = 15, 10Hz, (Dd, J = 9, 2 Hz, 1H), 7.58-7.84 (m, 2H) (m, 6 H).
[2058] Hydrochloride:
[2059] TLC: Rf 0.55 (ethyl acetate: methanol: triethylamine = 8: 2: 1);
[2060] _{NMR (DMSO-d 6):} δ 2.84 (s, 6H), 3.56 (m, 2H), 3.75 (dd, J = 15, 4Hz, 1H), 3.97 (dd, J = 15, 9Hz, 1H), 4.45 (m, 2H), 5.76 (dd, J = 9, 4 Hz, 1H), 7.22 (d, J = 2 Hz, 1H), 7.33 7.79 (m, 4H).
[2061] Example 24 (3a)
[2062] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene A solution of 6- (3- (N,
[2063]
[2064] Free body:
[2065] TLC: Rf 0.53 (ethyl acetate: methanol: triethylamine = 8: 2: 1);
[2066] _{NMR (CDCl 3): δ 1.97} (5 quint, J = 6.6Hz, 2H), 2.25 (s, 6H), 2.44 (t, J = 6.6Hz, 2H), 3.71 (dd, J = 14.6, 7.6Hz, J = 6.6 Hz, 2H), 5.00 (dd, J = 7.6, 5.6 Hz, 1H), 7.08 (d, J = 2.6 Hz, 1H), 7.23 (dd, J = 8.8,2.6 Hz, 1H), 7.46-7.54 (m, 2H), 7.63-7.72 (m, 3H), 7.85 (d, J = 8.8 Hz, 1H).
[2067] Hydrochloride:
[2068] TLC: Rf 0.53 (ethyl acetate: methanol: triethylamine = 8: 2: 1);
[2069] _{NMR (DMSO-d 6):} δ 2.17 (m, 2H), 2.78 (s, 6H), 3.20 (t, J = 7.9Hz, 2H), 3.77 (dd, J = 15.4, 3.2Hz, 1H), 4.00 (dd, J = 15.4, 9.4 Hz, 1H), 4.18 (t, J = 6.0 Hz, 2H), 5.71 (dd, J = 9.4, 3.2 Hz, 1H), 7.30-7.38 7.67 (m, 3 H), 7.75 - 7.79 (m, 3 H).
[2070] Example 24 (3b)
[2071] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene A solution of 6- (3- (N-cyanomethyl-
[2072]
[2073] TLC: Rf 0.33 (ethyl acetate: hexane: triethylamine = 6: 3: 1);
[2074] _{NMR (CDCl 3): δ 1.97} (5 quint, J = 6.5Hz, 2H), 2.38 (s, 3H), 2.65 (t, J = 6.5Hz, 2H), 3.54 (s, 2H), 3.71 (dd, J = 14.8, 7.8 Hz, 1H), 3.79 (dd, J = 14.8, 5.2 Hz, 1H), 4.06 J = 9.0, 2.6 Hz, 1H), 7.47-7.55 (m, 2H), 7.65-7.72 (m, 3H), 7.84 (d, J = 9.0 Hz, 1H).
[2075] Example 24 (4)
[2076] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2077]
[2078] Free body:
[2079] TLC: Rf 0.47 (ethyl acetate: methanol: triethylamine = 9: 1: 1);
[2080] NMR (CDCl ₃ ): δ 2.34 (s, 6H), 2.75 (t, J = 5.4 Hz, 2H), 3.74 (dd, J = 14.8, 7.8 Hz, 1H) J = 5.4 Hz, 2H), 5.00 (dd, J = 7.8, 5.4 Hz, 1H), 7.06 (d, J = 2.4 Hz, 1H), 7.28 2.4 Hz, 1H), 7.47-7.52 (m, 2H), 7.62-7.69 (m, 3H), 7.84 (d, J = 8.8 Hz, 1H).
[2081] Hydrochloride:
[2082] TLC: Rf 0.47 (ethyl acetate: methanol: triethylamine = 9: 1: 1);
[2083] _{NMR (DMSO-d 6):} δ 2.83 (d, J = 4.5Hz, 6H), 3.50-3.54 (m, 2H), 3.78 (dd, J = 15.0, 3.0Hz, 1H), 4.01 (dd, J = 1H), 7.41-7.44 (m, 2H), 7.60-7.67 (m, 3H, J = ), 7.77-7.80 (m, 3H), 10.83 (br, IH).
[2084] Example 24 (5)
[2085] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene hydrochloride
[2086]
[2087] TLC: Rf 0.32 (ethyl acetate: methanol: triethylamine = 16: 3: 1);
[2088] _{NMR (DMSO-d 6):} δ 7.85-7.60 (6H, m), 7.37 (1H, d, J = 8.2Hz), 7.22 (1H, d, J = 8.2Hz), 5.81 (1H, dd, J = 9.4, 3.2 Hz), 4.65-4.56 (2H, m), 3.97 (1H, dd, J = 15,9.4Hz), 3.75 (1H, dd, J = 15, 3.2Hz) 45 (2H, m), 2.82 (6H, s).
[2089] Example 25
[2090] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2091]
[2092] The compound prepared in Example 20 (39) was used instead of the compound prepared in Example 10, and the procedure of Example 11 was repeated to give the compound of the present invention having the following physical data.
[2093] TLC: Rf 0.34 (chloroform: tetrahydrofuran: 28% aqueous ammonia = 100: 50: 1);
[2094] _{NMR (DMSO-d 6):} δ 7.80-7.55 (4H, m), 7.49 (2H, t, J = 8Hz), 7.31 (2H, dd, J = 12, 8Hz), 7.02 (1H, t, J = D, J = 12 Hz), 6.60-6.45 (2H, m), 5.54 (1H, d, J = 9 Hz), 5.10 ), 4.20 (1H, d, J = 15 Hz), 3.98 (1H, dd, J = 15, 9 Hz).
[2095] Example 26
[2096] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene A solution of 4- (3- (pyridin-
[2097]
[2098] To the pyridine (6 ml) solution of the compound (143 mg) prepared in Example 25 was added nicotinyl chloride hydrochloride (77 mg). And the mixture was stirred at room temperature for 1.5 hours. Water was added to the reaction mixture and extracted with ethyl acetate. The extract was washed successively with water and a saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and concentrated. The residue was recrystallized with ethanol to obtain the compound (127 mg) of the present invention having the following physical properties.
[2099] TLC: Rf 0.34 (ethyl acetate: methanol: 28% ammonia water = 100: 10: 1);
[2100] _{NMR (DMSO-d 6):} δ 9.12 (1H, d, J = 2Hz), 8.77 (1H, dd, J = 5, 2Hz), 8.31 (1H, d, J = 8Hz), 7.82 (1H, s) D, J = 7 Hz), 5.59 (1H, d, J = 8.5 Hz), 5.11 (1H, d, J = 7 Hz), 7.78-7.52 (7H, m), 7.52-7.25 D, J = 15, 8.5 Hz), 4.86 (1H, d, J = 12 Hz), 4.20 (1H, d, J = 15 Hz).
[2101] Example 26 (1)
[2102] 3-ylcarbonylamino) ethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2103]
[2104] The procedure of Example 26 was repeated using the compound prepared in Example 23 instead of the compound prepared in Example 25, and if necessary, converted into the corresponding salt by a known method to give To obtain a compound of the present invention.
[2105] Free body:
[2106] TLC: Rf 0.43 (ethyl acetate: methanol: triethylamine = 8: 1: 1);
[2107] _{NMR (DMSO-d 6):} δ 3.36-3.55 (m, 2H), 3.81-3.88 (m, 1H), 4.02 (dd, J = 15.0, 8.7Hz, 1H), 4.04-4.10 (m, 1H), 7.31 (d, J = 7.2 Hz, 1H), 7.31 (d, J = 8.1 Hz, 1H) ), 7.48 (dd, J = 8.1, 4.8 Hz, 1H), 7.56-7.68 (m, 3H), 7.71-7.77 (m, 3H), 8.15 (dt, J = 8.1, 1.8 Hz, 1H) 8.68 (m, 1H), 8.68 (dd, J = 4.8, 1.8 Hz, 1H), 8.98 (d, J = 1.8 Hz, 1H).
[2108] Hydrochloride:
[2109] TLC: Rf 0.43 (ethyl acetate: methanol: triethylamine = 8: 1: 1);
[2110] _{NMR (DMSO-d 6):} δ 3.41-3.56 (m, 2H), 3.83-3.89 (m, 1H), 4.01 (dd, J = 15.0, 8.7Hz, 1H), 4.07-4.12 (m, 1H), 8.14 (d, J = 15.0, 1.2 Hz, 1H), 5.67 (d-form, J = 7.5 Hz, 1H), 7.31 ), 7.56-7.61 (m, 2H), 7.65 (t, J = 8.0 Hz, 1H), 7.71-7.76 (m, 3H), 7.83 (dd, J = 8.1, 5.4 Hz, 1H) J = 8.1, 1.6 Hz, 1H), 8.87 (dd, J = 5.4, 1.6 Hz, 1H), 9.10 (t, J = 5.4 Hz, 1H), 9.19 (d, J = 1.6 Hz, 1H).
[2111] Example 27
[2112] 5-Methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxo [
[2113]
[2114] (0.5 ml), acetic acid (0.4 ml) and sodium benzenesulfonate (940 mg) were sequentially added to a solution of 5-methyl-1,1-dioxide benzo [b] thiophene (353 mg) in ethanol (19.5 ml) . The reaction mixture was refluxed for 7 hours. The reaction mixture was cooled to room temperature, and the precipitated crystals were collected by filtration. The crystals were washed sequentially with water, ethanol and hexane to obtain the compound (381 mg) of the present invention having the following physical data.
[2115] TLC: Rf 0.32 (hexane: AcOEt = 1: 1);
[2116] NMR (CDCl ₃ ): 2.52 (s, 3H), 3.66 (dd, J = 14.6, 8.7 Hz, 1H), 3.77 (dd, J = 14.6, 4.9 Hz, 1H) 4.9 Hz, 1 H), 7.41-7.57 (m, 4H), 7.64-7.69 (m, 3H), 7.80 (s-form, 1H).
[2117] Example 27 (1) to Example 27 (5)
[2118] 5-methyl-1,1-dioxide The procedure of Example 27 was repeated using the benzo [b] thiophene compound instead of benzo [b] thiophene to obtain the compound of the present invention shown below.
[2119] Example 27 (1)
[2120] Amino-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2121]
[2122] TLC: Rf 0.27 (dichloromethane: ethyl acetate = 8: 1);
[2123] _{NMR (DMSO-d 6):} δ 3.74 (dd, J = 15.1, 3.7Hz, 1H), 3.95 (dd, J = 15.1, 9.3Hz, 1H), 5.83 (dd, J = 9.3, 3.7Hz, 1H) (M, 2H), 7.58-7.65 (m, 2H), 7.66 (d, J = 8.7 Hz, 2H), 7.73-7.83 , 2.0 Hz, 1 H), 8.40 (d, J = 2.0 Hz, 1 H), 10.86 (s, 1 H).
[2124] Example 27 (2)
[2125] 4-Cyano-3-phenylsulfonyl-2,3-dihydro-1,1-dioxo [b] thiophene
[2126]
[2127] TLC: Rf 0.60 (dichloromethane: ethyl acetate = 8: 1);
[2128] _{NMR (DMSO-d 6):} δ 3.95 (dd, J = 15, 10Hz, 1H), 4.15 (d, J = 15Hz, 1H), 5.80 (d, J = 10Hz, 1H), 7.60-7.80 (m, 2H), 7.80-7.90 (m, 3H), 7.95 (t, J = 7.5 Hz, 1H), 8.20 (d, J = 7.5 Hz, 1H), 8.35 (d, J = 7.5 Hz, 1H).
[2129] Example 27 (3)
[2130] Nitro-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2131]
[2132] TLC: Rf 0.44 (hexane: AcOEt = 1: 1);
[2133] _{NMR (DMSO-d 6):} δ 3.97 (dd, J = 15.3, 3.0Hz, 1H), 4.16 (dd, J = 15.3, 9.3Hz, 1H), 6.00 (dd, J = 9.3, 3.0Hz, 1H) , 7.62-7.67 (m, 2H), 7.79-7.83 (m, 3H), 8.02 (d, J = 8.4 Hz, 1H) , 1H).
[2134] Example 27 (4)
[2135] 4,7-Dimethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2136]
[2137] TLC: Rf 0.48 (ethyl acetate);
[2138] _{NMR (DMSO-d 6):} δ 3.27 (s, 3H), 3.85 (s, 3H), 3.96 (dd, J = 15.2, 8.8Hz, 1H), 4.12 (dd, J = 15.2, 1.5Hz, 1H) , 5.49 (dd, J = 8.8,1.5Hz, 1H), 7.12 (d, J = 9.0Hz, 1H), 7.21 (d, J = 9.0Hz, 1H), 7.60-7.78 (m, 5H).
[2139] Example 27 (5)
[2140] 3,7-bis (3-hydroxypropyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2141]
[2142] TLC: Rf 0.34 (ethyl acetate: methanol = 9: 1);
[2143] _{NMR (DMSO-d 6):} δ 1.52-1.57 (m, 2H), 1.83 (5 quint, J = 6.3Hz, 2H), 3.43 (q, J = 6.3Hz, 2H), 3.55 (q, J = 5.8 J = 14.8 Hz, 1H), 3.60-3.67 (m, 1H), 3.80-3.87 (m, J = 5.1 Hz, 1H), 4.54 (d, J = 7.8 Hz, 1H), 7.14 (t, J = d, J = 9.0 Hz, 1H), 7.20 (d, J = 9.0 Hz, 1H), 7.58-7.63 (m, 2H), 7.72-7.77 (m, 3H).
[2144] Example 28
[2145] 4- (pyridin-3-ylmethyl) carbamoyl-l, l-dioxide benzo [b] thiophene
[2146]
[2147] Thionyl chloride (2.0 mL) was added to 4-carboxy-1,1-dioxide benzo [b] thiophene (prepared by the method described in the following Example 107) (270 mg) Lt; / RTI &gt; Methylene chloride (4.0 ml) solution of the previously obtained chloride was added dropwise to (pyridin-3-ylmethyl) amine (154 mg) dissolved in methylene chloride (6.0 ml) and triethylamine (260 mg), followed by stirring at room temperature for 2 hours . To the reaction mixture was added ice water and a 1N aqueous solution of sodium hydroxide (1.5 ml) and extracted with ethyl acetate (40 ml). The extract was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was recrystallized from a mixed solvent of ethyl acetate and hexane to obtain the compound (330 mg) of the present invention having the following physical data.
[2148] TLC: Rf 0.48 (methylene chloride: methanol = 10: 1);
[2149] NMR (CDCl ₃ ): 8.56 (d, J = 2.1 Hz, 1H), 8.53 (dd, J = 4.5, 2.1 Hz, 1H), 7.93 (dd, J = 7.2, 0.6 Hz, 1H), 7.79-7.72 (t, J = 7.8 Hz, 1H), 7.31 (dd, J = 7.8, 4.5 Hz, 1H), 6.86 (t, J = 6.3 Hz, 1H), 6.77 (d, J = 7.2 Hz, 1H), 4.65 (d, J = 6.3 Hz, 2H).
[2150] Examples 28 (1) to 28 (33)
[2151] 4-carboxy-1,1-dioxide benzo [b] thiophene was treated in the same manner as in Example 28 using an amine derivative corresponding to the corresponding carboxylic acid and (pyridin-3-ylmethyl) amine , And if necessary, converted into the corresponding salt by a known method to obtain the following compound of the present invention.
[2152] Further, in the production of the compound of Example 28 (33), 4-aminomethyl-1,1-dioxide benzo [b] thiophene and pyridine-3-ylcarboxylic acid were reacted.
[2153] Example 28 (1)
[2154] 4- (4-benzylpiperazin-1-yl) carbonyl-1, 1-dioxide benzo [b] thiophene
[2155]
[2156] TLC: Rf 0.30 (ethyl acetate: methanol = 50: 1);
[2157] _{NMR (CDCl 3): δ 7.75} (d, J = 7.4Hz, 1H), 7.56 (t, J = 7.4Hz, 1H), 7.47 (d, J = 7.4Hz, 1H), 7.40-7.20 (m, 6H ), 6.78 (d, J = 7.0 Hz, 1H), 3.83 (m, 2H), 3.55 (s, 2H), 3.34 (m, 2H), 2.55 (m,
[2158] Example 28 (2)
[2159] 4- (N- (2- (pyridin-3-yl) ethyl) -N-methylcarbamoyl) -1,1-dioxide benzo [b] thiophene
[2160]
[2161] MS (APCI, Pos.): M / z 361 (M + MeOH + H) &lt; ⁺ & gt ^; , 329 (m + H) &lt; ⁺ &gt;
[2162] Example 28 (3)
[2163] 4- (2- (2-hydroxyethoxy) ethyl) carbamoyl-1,1-dioxide benzo [b] thiophene
[2164]
[2165] MS (APCI, Pos.): M / z 330 (M + MeOH + H) ⁺ , 298 (M + H) ⁺ .
[2166] Example 28 (4)
[2167] 4- (2,4-dimethoxyphenylmethyl) carbamoyl-l, l-dioxide benzo [b] thiophene
[2168]
[2169] TLC: Rf 0.68 (ethyl acetate);
[2170] _{NMR (CDCl 3): δ 7.90} (d, J = 7.5Hz, 1H), 7.75 (d, J = 7.5Hz, 1H), 7.60 (d, J = 7.5Hz, 1H), 7.55 (t, J = 7.5 J = 7.5 Hz, 2H), 3.85 (d, J = 7.5 Hz, 1H), 7.25 (s, 3H), 3.80 (s, 3H).
[2171] Example 28 (5)
[2172] 4- (1-benzylpiperidin-4-yl) carbamoyl-l, l-dioxide benzo [b] thiophene
[2173]
[2174] Free body:
[2175] TLC: Rf 0.50 (ethyl acetate: methanol = 8: 1.5);
[2176] _{NMR (CDCl 3): δ 7.90} (d, J = 7.5Hz, 1H), 7.80 (d, J = 7.5Hz, 1H), 7.60 (d, J = 7.5Hz, 1H), 7.55 (t, J = 7.5 2H), 3.55 (s, 2H), 6.40 (d, J = 7.5 Hz, , 3.00-2.90 (m, 2H), 2.30-2.10 (m, 2H), 2.10-1.90 (m, 2H), 1.70-1.50 (m, 2H).
[2177] Hydrochloride:
[2178] TLC: Rf 0.44 (methanol: ethyl acetate = 1: 10);
[2179] _{NMR (CD 3 OD): δ} 7.90-7.75 (m, 3H), 7.75-7.45 (m, 6H), 7.08 (d, J = 7.0Hz, 1H), 4.34 (s, 2H), 4.27-4.05 (m 2H), 2.34-2.15 (m, 2H), 2.12-1.81 (m, 2H), 3.61-3.42 (m, 2H).
[2180] Methanesulfonate:
[2181] TLC: Rf 0.44 (methanol: ethyl acetate = 1: 10);
[2182] _{NMR (CD 3 OD): δ} 7.89-7.74 (m, 3H), 7.73-7.60 (m, 1H), 7.60-7.45 (m, 5H), 7.08 (d, J = 7.0Hz, 1H), 4.34 (s , 2H), 4.27-4.03 (m, 1H), 3.68-3.38 (m, 2H), 3.38-3.06 (m, 2H), 2.67 (s, 3H), 2.38-1.72 (m, 4H).
[2183] Example 28 (6)
[2184] 4- (pyridin-4-ylmethyl) carbamoyl-l, l-dioxide benzo [b] thiophene
[2185]
[2186] TLC: Rf 0.29 (ethyl acetate: methanol = 19: 1);
[2187] NMR (CDCl ₃ + CD ₃ OD): δ 8.50 (d, J = 7 Hz, 2H), 8.25 (broad t, J = 7 Hz, 1H)
[2188] (d, J = 7 Hz, 1H), 7.80 (d, J = 8 Hz, 2H), 7.60 , &Lt; / RTI &gt; 1H), 4.60 (d, J = 7 Hz, 2H).
[2189] Example 28 (7)
[2190] 4- (2-t-butoxycarbonylethyl) carbamoyl-1,1-dioxide benzo [b] thiophene
[2191]
[2192] TLC: Rf 0.40 (AcOEt: hexane = 3: 2);
[2193] _{NMR (CDCl 3): δ 8.00} (d, J = 7Hz, 1H), 7.80 (d, J = 8Hz, 1H), 7.70 (d, J = 8Hz, 1H), 7.60 (t, J = 8Hz, 1H) , 6.95 (broad-s, 1H), 6.80 (d, J = 7 Hz, 1H), 3.70 (q, J = 7 Hz, 2H), 2.60 (t, J = 7 Hz, 2H), 1.45 (s, 9H).
[2194] Example 28 (8)
[2195] 4- (thiophen-2-ylmethyl) carbamoyl-l, l-dioxide benzo [b] thiophene
[2196]
[2197] TLC: Rf 0.48 (CHCl 3: MeOH = 9: 1);
[2198] _{NMR (CDCl 3 + DMSO-d} 6): δ 8.50 (t, J = 7Hz, 1H), 7.95 (d, J = 6Hz, 1H), 7.85 (d, J = 8Hz, 1H), 7.75 (d, J J = 6 Hz, 1H), 7.05 (d, J = 3 Hz, 1H), 6.95 (dd, J = 3 Hz and 6 Hz, 1H), 7.55 ), 6.80 (d, J = 6 Hz, 1H), 4.75 (d, J = 7 Hz, 2H).
[2199] Example 28 (9)
[2200] 4-Benzylcarbamoyl-l, l-dioxide &lt; / RTI &gt; benzo [b] thiophene
[2201]
[2202] TLC: Rf 040 (ethyl acetate: hexane = 1: 1);
[2203] _{NMR (CDCl 3 + DMSO-d} 6): δ 7.99 (d, J = 7.2Hz, 1H), 7.81-7.75 (m, 2H), 7.56 (t, J = 7.5Hz, 1H), 7.43 (t, J = 5.7 Hz, 1H), 7.40-7.27 (m, 5H), 6.78 (d, J = 7.2 Hz, 1H), 4.63 (d, J = 5.7 Hz, 2H).
[2204] Example 28 (10)
[2205] 4- (pyridin-2-ylmethyl) carbamoyl-l, l-dioxide benzo [b] thiophene
[2206]
[2207] TLC: Rf 0.30 (ethyl acetate: hexane = 1: 1);
[2208] _{NMR (CDCl 3): δ 8.56} (d, J = 5.1Hz, 1H), 8.05 (dd, J = 7.2, 0.9Hz, 1H), 7.84 (t, J = 7.2Hz, 1H), 7.73 (dt, J = 0.9, 7.8 Hz, 1H), 7.68 (t, J = 5.1 Hz, 1H), 7.61 (t, J = 7.8 Hz, 1H), 7.33 (d, J = 7.8 Hz, 1H) (D, J = 6.9 Hz, 1H), 4.76 (d, J = 5.1 Hz, 2H).
[2209] Example 28 (11)
[2210] 4- (2- (piperidin-1-yl) ethyl) carbamoyl-l, l-dioxide benzo [b] thiophene
[2211]
[2212] Free body:
[2213] TLC: Rf 0.35 (methylene chloride: methanol = 10: 1);
[2214] _{NMR (CDCl 3): δ 8.04} (dd, J-7.2, 0.9Hz, 1H), 7.80 (dt, J = 7.8, 0.9Hz, 1H), 7.72 (dd, J = 7.8, 0.9Hz, 1H), 7.59 (t, J = 7.8 Hz, 1H), 7.02 (bs, 1H), 6.77 (d, J = 7.2 Hz, 1H), 3.54 , 2H), 2.50-2.40 (m, 4H), 1.76-1.43 (m, 6H).
[2215] Hydrochloride:
[2216] TLC: Rf 0.60 (methylene chloride: methanol: triethylamine = 8: 1.5: 0.5);
[2217] _{NMR (DMSO-d 6):} δ 10.20 (. Br s, 1H), 9.25-9.10 (m, 1H), 8.01 (d, J = 7.0Hz, 1H), 7.99 (d, J = 7.0Hz, 1H) , 7.93 (d, J = 6.9 Hz, 1H), 7.73 (t, J = 7.0 Hz, 1H), 7.47 (d, J = 6.9 Hz, 1H), 3.80-3.60 m, 2H), 3.45-3.15 (m, 2H), 3.10-2.80 (m, 2H), 2.00-1.70 (m, 5H), 1.55-1.30 (m,
[2218] Example 28 (12)
[2219] 4 - ((1S) -1-t-butoxycarbonyl-2-methylpropyl) carbamoyl-1,1-dioxide benzo [b] thiophene
[2220]
[2221] TLC: Rf 0.48 (hexane: AcOEt = 1: 1);
[2222] _{NMR (CDCl 3): δ 7.95} (d, J = 7.2Hz, 1H), 7.81 (d, J = 7.8Hz, 1H), 7.77 (d, J = 7.8Hz, 1H), 7.59 (t, J = 7.8 J = 8.4 Hz, 1H), 4.64 (dd, J = 8.4, 4.2 Hz, 1H), 2.36-2.27 (m, 1H, ), 1.51 (s, 9H), 1.02 (d, J = 6.9 Hz, 3H), 0.98 (d, J = 6.9 Hz, 3H).
[2223] Example 28 (13)
[2224] 4- (2-fluorophenylmethyl) carbamoyl-1, 1-dioxo [b] thiophene
[2225]
[2226] TLC: Rf 0.60 (CHCl 3: MeOH = 9: 1);
[2227] _{NMR (CDCl 3 + DMSO-d} 6): δ 7.95 (broad peak, 1H), 7.95 (d, J = 7Hz, 1H), 7.80 (d, J = 8Hz, 1H), 7.78 (d, J = 8Hz, J = 7 Hz, 1H), 4.62 (d, J = 7 Hz, 1H), 7.55 (t, J = 8 Hz, 1H), 7.50-7.20 (m, 2H), 7.20-7.00 , 2H).
[2228] Example 28 (14)
[2229] 4- (3-fluorophenylmethyl) carbamoyl-l, l-dioxo [b] thiophene
[2230]
[2231] TLC: Rf 0.50 (CHCl 3: MeOH = 9: 1);
[2232] _{NMR (CDCl 3 + DMSO-d} 6): δ 8.40 (broad peak, 1H), 7.98 (d, J = 7Hz, 1H), 7.85 (d, J = 8Hz, 1H), 7.80 (d, J = 8Hz, J = 7 Hz, 1H), 4.60 (d, J = 7 Hz, 1H), 7.55 (t, J = 8 Hz, 1H), 7.40-7.25 (m, 1H), 7.20-6.90 , 2H).
[2233] Example 28 (15)
[2234] 4- (3-methylphenylmethyl) carbamoyl-l, l-dioxo [b] thiophene
[2235]
[2236] TLC: Rf 0.60 (CHCl 3: MeOH = 9: 1);
[2237] _{NMR (CDCl 3): δ 7.95} (d, J = 7Hz, 1H), 7.75 (d, J = 8Hz, 1H), 7.65 (d, J = 8Hz, 1H), 7.52 (t, J = 8Hz, 1H) , 7.40-7.20 (m, 3H), 6.75 (d, J = 7 Hz, 1H), 6.40 (s, 3 H).
[2238] Example 28 (16)
[2239] 4- (2-methoxyphenylmethyl) carbamoyl-l, l-dioxide benzo [b] thiophene
[2240]
[2241] TLC: Rf 0.64 (CHCl 3: MeOH = 9: 1);
[2242] NMR (CDCl ₃ + DMSO-d ₆ ): 隆 7.93 (d, J = 7 Hz, 1H), 7.85-7.70 (m, 3H), 7.55
[2243] (D, J = 7 Hz, 1H), 7.30 (m, 2H), 6.92 (m, 2H), 6.78
[2244] Example 28 (17)
[2245] 4- (2, 3-dimethoxyphenylmethyl) carbamoyl-l, l-dioxide benzo [b] thiophene
[2246]
[2247] TLC: Rf 0.63 (CHCl 3: MeOH = 9: 1);
[2248] NMR (CDCl ₃ + DMSO-d ₆ ): 隆 7.97 (d, J = 7.2 Hz, 1H), 7.77 (d, J = 7.6 Hz, 1H) (t, J = 7.8 Hz, 1H), 7.00-6.85 (m, 2H), 6.77 (d, J = 7.2 Hz, 1H) , 4.63 (d, J = 5.6 Hz, 2H), 3.90 (s, 3H), 3.88 (s, 3H).
[2249] Example 28 (18)
[2250] 4- (3,4-dimethoxyphenylmethyl) carbamoyl-l, l-dioxide benzo [b] thiophene
[2251]
[2252] TLC: Rf 0.53 (CHCl 3: MeOH = 9: 1);
[2253] _{NMR (CDCl 3 + DMSO-d} 6): δ 8.57 (t- type, J = 5.8Hz, 1H), 7.97 (d, J = 7.2Hz, 1H), 7.86 (d, J = 7.8Hz, 1H), 4.77 (d, J = 7.8 Hz, 1H), 7.57 (t, J = 7.8 Hz, 1H), 7.00-6.80 (m, 4H), 4.53 ), 3.87 (s, 3H).
[2254] Example 28 (19)
[2255] 4- (2,5-difluorophenylmethyl) carbamoyl-l, l-dioxide benzo [b] thiophene
[2256]
[2257] TLC: Rf 0.45 (CHCl 3: MeOH = 9: 1);
[2258] _{NMR (CDCl 3 + DMSO-d} 6): δ 8.78 (t, J = 6.0Hz, 1H), 7.97 (dd, J = 7.0Hz and 1.0Hz, 1H), 7.89 (dd , J = 7.6Hz and 1.0Hz J = 7.6 Hz, 1H), 7.79 (d, J = 7.6 Hz, 1H), 7.59 (t, J = 7.6 Hz, 1H), 7.20-6.90 (d, J = 6.0 Hz, 1H).
[2259] Example 28 (20)
[2260] 4- (3,4,5-trimethoxyphenylmethyl) carbamoyl-l, l-dioxide benzo [b] thiophene
[2261]
[2262] TLC: Rf 0.33 (CHCl 3: MeOH = 9: 1);
[2263] _{NMR (CDCl 3 + DMSO-d} 6): δ 8.00 (broad peak, 1H), 7.98 (dd, J = 7.2Hz and 1.0Hz, 1H), 7.82 (dd , J = 7.6Hz and 1.0Hz, 1H), 7.78 (d, J = 7.6 Hz, 1H), 7.56 (t, J = 7.6 Hz, 1H), 6.79 Hz, 2H), 3.86 (s, 6H), 3.83 (s, 3H).
[2264] Example 28 (21)
[2265] 4- (Benzimidazol-2-ylmethyl) carbamoyl-l, l-dioxide benzo [b] thiophene
[2266]
[2267] TLC: Rf 0.28 (CHCl 3: MeOH = 9: 1);
[2268] _{NMR (CDCl 3 + DMSO-d} 6): δ 8.97 (t, J = 5.6Hz, 1H), 8.08 (d, J = 7.2Hz, 1H), 7.94 (dd, J = 7.8Hz and 1.0Hz, 1H) , 7.79 (dd, J = 7.8 Hz and 1.0 Hz, 1H), 7.62-7.50 (m, 3H), 7.30-7.15 (m, 2H), 6.81 (d, J = 7.2 Hz, 1H) J = 5.6 Hz, 2H).
[2269] Example 28 (22)
[2270] 4- (3,5-difluorophenylmethyl) carbamoyl-l, l-dioxide benzo [b] thiophene
[2271]
[2272] TLC: Rf 0.57 (CHCl 3: MeOH = 9: 1);
[2273] _{NMR (CDCl 3 + DMSO-d} 6): δ 9.11 (t, J = 5.8Hz, 1H), 7.98 (dd, J = 7.2Hz and 1.0Hz, 1H), 7.93 (dd , J = 7.6Hz and 1.0Hz J = 7.6 Hz, 1H), 7.81 (d, J = 7.6 Hz, 1H), 7.62 (t, J = 7.6 Hz, 1H), 7.00-6.90 -6.68 (m, 1 H), 4.55 (d, J = 5.8 Hz, 2 H).
[2274] Example 28 (23)
[2275] 4- (N-benzyl-N-methylcarbamoyl) -1,1-dioxide benzo [b] thiophene
[2276]
[2277] TLC: Rf 0.69 (CHCl 3: MeOH = 9: 1);
[2278] _{NMR (CDCl 3): δ 7.80-7.70} (m, 1H), 7.65-7.47 (m, 2H), 7.47-7.25 (m, 5H), 7.15-7.00 (m, 1H), 6.80-6.72 (m, 1H ), 4.78 and 4.44 (s, total 2H), 3.12 and 2.84 (s, total 3H, respectively).
[2279] Example 28 (24)
[2280] 4- (4-nitrophenylmethyl) carbamoyl-l, l-dioxide benzo [b] thiophene
[2281]
[2282] TLC: Rf 0.44 (CHCl 3: MeOH = 9: 1);
[2283] _{NMR (CDCl 3 + DMSO-d} 6): δ 9.20 (t, J = 5.8Hz, 1H), 8.20 (d, J = 8Hz, 2H), 7.98 (d, J = 7Hz, 1H), 7.93 (d, J = 7.5 Hz, 1H), 7.81 (d, J = 7.5 Hz, 1H), 7.62 , &Lt; / RTI &gt; 1H), 4.67 (d, J = 5.8 Hz, 2H).
[2284] Example 28 (25)
[2285] 5- (2-hydroxyethyl) carbamoyl-l, l-dioxide benzo [b] thiophene
[2286]
[2287] TLC: Rf 0.38 (ethyl acetate);
[2288] _{NMR (CDCl 3 + CD 3 OD} ): δ 7.98 (dd, J = 8.0Hz, 1.2Hz, 1H), 7.88 (d, J = 1.2Hz, 1H), 7.77 (d, J = 8.0Hz, 1H), (T, J = 4.8 Hz, 2H), 7.31 (d, J = 6.8 Hz, 1H), 6.81 (d, J = 6.8 Hz, 1H).
[2289] Example 28 (26)
[2290] 5- (Pyridin-3-ylmethyl) carbamoyl-4-methoxy-l, l-dioxide benzo [b] thiophene
[2291]
[2292] MS (APCI, Pos.): M / z 363 (M + MeOH + H) ⁺ , 331 (M + H) ⁺ .
[2293] Example 28 (27)
[2294] 5- (2-Dimethylaminoethyl) carbamoyl-4-methoxy-1,1-dioxo [b] thiophene
[2295]
[2296] TLC: Rf 0.27 (methylene chloride: methanol = 10: 1);
[2297] _{NMR (CDCl 3): δ 8.23} (d, J = 8.1Hz, 1H), 8.03 (t, J = 5.7Hz, 1H), 7.55 (d, J = 8.1Hz, 1H), 7.41 (d, J = 6.9 J = 5.7 Hz, 2H), 2.30 (d, J = 6.7 Hz, 1H), 6.76 s, 6H).
[2298] Example 28 (28)
[2299] 5-Dimethylcarbamoyl-4-methoxy-l, l-dioxide benzo [b] thiophene
[2300]
[2301] TLC: Rf 0.35 (methanol: ethyl acetate = 5: 95);
[2302] _{NMR (CDCl 3): δ 7.52-7.38} (m, 3H), 6.75 (d, J = 7.4Hz, 1H), 3.93 (s, 3H), 3.15 (s, 3H), 2.88 (s, 3H).
[2303] Example 28 (29)
[2304] 5 - (2,3,4,5,6,7-hexahydro-1H-azepin-1-yl) carbonyl-4-methoxy- 1,1-dioxide benzo [b] thiophene
[2305]
[2306] TLC: Rf 0.60 (methylene chloride: methanol = 10: 1);
[2307] _{NMR (CDCl 3): δ 7.48} (dd, J = 7.5, 0.9Hz, 1H), 7.42 (dd, J = 6.9, 0.9Hz, 1H), 7.38 (d, J = 7.5Hz, 1H), 6.74 (d 2H), 1.90-1.75 (m, 2H), 1.75-1.40 (m, 6H), 3.80-3.56 (m, ).
[2308] Example 28 (30)
[2309] 5- (2,3-dihydroindol-1-yl) carbonyl-4-methoxy-1,1-dioxide benzo [b] thiophene
[2310]
[2311] TLC: Rf 0.82 (methylene chloride: methanol = 10: 1);
[2312] _{NMR (CDCl 3): δ 8.31} (d, J = 7.8Hz, 1H), 7.54 (s, 2H), 7.45 (d, J = 6.9Hz, 1H), 7.33-7.20 (m, 2H), 7.20-7.07 (m, 1H), 6.77 (d, J = 6.9 Hz, 1H), 3.97 (s, 3H), 3.90-3.66 (m, 2H), 3.25-3.10 (m, 2H).
[2313] Example 28 (31)
[2314] 1-yl) carbonyl-4-methoxy-1,1-dioxide benzo [b] thiophene
[2315]
[2316] TLC: Rf 0.30 (ethyl acetate: hexane = 1: 1);
[2317] _{NMR (CDCl 3): δ 7.51} (d, J = 7.8Hz, 1H), 7.46 (d, J = 7.8Hz, 1H), 7.43-7.35 (m, 2H), 7.30-7.20 (m, 1H), 7.06 2H), 6.76 (d, J = 6.9 Hz, 1H), 4.10-3.90 (m, 2H), 3.98 (s, 3H), 3.54-3.37 (m, 2H), 3.20-2.90 , 4H).
[2318] Example 28 (32)
[2319] 1-yl) carbonyl-4-methoxy-1,1-dioxide benzo [b] thiophene A solution of 5- (4- (2- (2-trifluoromethylphenyl) ethyl) piperazin-
[2320]
[2321] TLC: Rf 0.33 (ethyl acetate);
[2322] _{NMR (CDCl 3): δ 7.63} (d, J = 7.8Hz, 1H), 7.49 (d, J = 7.5Hz, 2H), 7.46-7.40 (m, 2H), 7.40-7.27 (m, 2H), 6.75 (d, J = 7.5 Hz, 1H), 3.94 (s, 3H), 3.90-3.80 (m, 2H), 3.35-3.20 (m, 2H), 3.04-2.94 , 4H), 2.58-2.40 (m, 2H).
[2323] Example 28 (33)
[2324] Preparation of 4- (pyridin-3-ylcarbonyl) aminomethyl-1,1-dioxide benzo [b] thiophene
[2325]
[2326] MS (APCI, Pos.): M / z 333 (M + MeOH + H) ⁺ , 301 (M + H) ⁺ .
[2327] Example 29
[2328] 4- (3- (pyrrol-1-yl) propyl) oxy-1,1-dioxide benzo [b] thiophene
[2329]
[2330] (630 mg) and 1- (3-hydroxypropyl) pyrrole (300 mg) were dissolved in anhydrous tetrahydrofuran (5 ml) 15 ml), and an anhydrous tetrahydrofuran (4 ml) solution of diethyl azodicarboxylate (323 mg) was added dropwise under argon gas atmosphere, followed by stirring at room temperature for 2 hours. Methanol (3 ml) was added to the reaction mixture and the mixture was stirred for 10 minutes. The reaction mixture was concentrated. The residue was purified by silica gel column chromatography (hexane: ethyl acetate = 2: 1) to obtain the compound (473 mg) of the present invention having the following physical data.
[2331] TLC: Rf 0.47 (hexane: AcOEt = 1: 1);
[2332] _{NMR (CDCl 3): δ 7.55-7.35} (m, 2H), 7.30 (d, J = 8Hz, 1H), 6.97 (d, J = 8Hz, 1H), 6.75-6.54 (m, 3H), 6.16 (t 2H), 4.12 (t, J = 6 Hz, 2H), 4.00 (t, J = 6 Hz, 2H), 2.27 (q, J = 6 Hz, 2H).
[2333] Examples 30 to 30 (13)
[2334] The operation was carried out in the same manner as in Example 18 using an alcohol derivative corresponding to the compound prepared in Example 9 (12) and a halide corresponding to 4-nitrobenzyl bromide, , 1-dioxide benzo [b] thiophene, and the corresponding alcohol derivative to 1- (3-hydroxypropyl) pyrrole were used in the same manner as in Example 29 to give the following compounds of the present invention &Lt; / RTI &gt;
[2335] Example 30
[2336] 4- (quinolin-2-ylmethyl) oxy-1, 1-dioxide benzo [b] thiophene
[2337]
[2338] TLC: Rf 0.27 (hexane: AcOEt = 1: 1);
[2339] _{NMR (CDCl 3): δ 8.23} (d, J = 8Hz, 1H), 8.09 (d, J = 8Hz, 1H), 7.95-7.68 (m, 2H), 7.68-7.50 (m, 3H), 7.50-7.22 (m, 2H), 7.14 (d, J = 8 Hz, 1H), 6.66 (d, J = 7 Hz, 1H), 5.49 (s, 2H).
[2340] Example 30 (1)
[2341] 4- (2- (pyrrol-1-yl) ethyl) oxy-1,1-dioxide benzo [b] thiophene
[2342]
[2343] TLC: Rf 0.50 (ethyl acetate: hexane = 2: 1);
[2344] _{NMR (CDCl 3): δ 7.55-7.22} (m, 3H), 6.94 (d, J = 8Hz, 1H), 6.73 (t, J = 2Hz, 2H), 6.62 (d, J = 7Hz, 1H), 6.19 (t, J = 2 Hz, 2H), 4.32 (s, 4H).
[2345] Example 30 (2)
[2346] 4- (2- (4-methylthiazol-5-yl) ethyl) oxy-1,1-dioxide benzo [b] thiophene
[2347]
[2348] TLC: Rf 0.15 (ethyl acetate: hexane = 2: 1);
[2349] _{NMR (CDCl 3): δ 8.63} (s, 1H), 7.58-7.37 (m, 2H), 7.31 (d, J = 8Hz, 1H), 7.03 (d, J = 8Hz, 1H), 6.64 (d, J = 8 Hz, 1H), 4.26 (t, J = 6 Hz, 2H), 3.31 (t, J = 6 Hz, 2H), 2.46 (s, 3H).
[2350] Example 30 (3)
[2351] 4- (3- (pyridin-4-yl) propyl) oxy-1,1-dioxide benzo [b] thiophene
[2352]
[2353] TLC: Rf 0.36 (ethyl acetate: methanol = 10: 1);
[2354] _{NMR (CDCl 3): δ 8.53} (dd, J = 1.6, 4.5Hz, 2H), 7.60-7.22 (m, 3H), 7.14 (d, J = 5.8Hz, 2H), 7.00 (d, J = 8.0Hz J = 6.2 Hz, 2H), 2.84 (t, J = 7.4 Hz, 2H), 2.19 (quintet, J = 6.2 Hz, 2H).
[2355] Example 30 (4)
[2356] 4- (1-t-butoxycarbonylpiperidin-3-ylmethyl) oxy-1, 1-dioxide benzo [b] thiophene
[2357]
[2358] TLC: Rf 0.46 (hexane: AcOEt = 1: 1);
[2359] _{NMR (CDCl 3): δ 7.58-7.38} (m, 2H), 7.30 (d, J = 7.6Hz, 1H), 7.04 (d, J = 8.2Hz, 1H), 6.61 (d, J = 7.0Hz, 3.15 -2.50 (m, 4H), 1.45 (s, 9H).
[2360] Example 30 (5)
[2361] 4- (2- (pyrrolidin-1-yl) ethyl) oxy-1,1-dioxide benzo [b] thiophene
[2362]
[2363] TLC: Rf 0.36 (ethyl acetate: acetic acid: water = 3: 1: 1);
[2364] _{NMR (CDCl 3): δ 7.55-7.35} (m, 2H), 7.29 (d, J = 7Hz, 1H), 7.06 (d, J = 8Hz, 1H), 6.61 (d, J = 7Hz, 1H), 4.22 (t, J = 6 Hz, 2H), 2.94 (t, J = 6 Hz, 2H), 2.64 (t, J = 6 Hz, 4H), 2.20 - 1.65 (m, 4H).
[2365] Example 30 (6)
[2366] 4 - (2- (Piperidin-1-yl) ethyl) oxy-1, 1-dioxide benzo [b] thiophene
[2367]
[2368] TLC: Rf 0.44 (ethyl acetate: acetic acid: water = 3: 1: 1);
[2369] _{NMR (CDCl 3): δ 7.60-7.58} (m, 2H), 7.29 (d, J = 8Hz, 1H), 7.07 (d, J = 8Hz, 1H), 6.61 (d, J = 7Hz, 1H), 4.21 (t, J = 6 Hz, 2H), 2.80 (t, J = 6 Hz, 2H), 2.51 (t, J = 6 Hz, 4H), 1.90-1.35 (m 6H).
[2370] Example 30 (7)
[2371] 4- (2- (2-acetyloxyethoxy) ethyl) oxy-1,1-dioxide benzo [b] thiophene
[2372]
[2373] TLC: Rf 0.46 (ethyl acetate: hexane = 2: 1);
[2374] _{NMR (CDCl 3): δ 7.58-7.38} (m, 2H), 7.31 (d, J = 7Hz, 1H), 7.08 (d, J = 9Hz, 1H), 6.62 (d, J = 7Hz, 1H), 4.25 (t, J = 5 Hz, 4H), 3.88 (t, J = 5 Hz, 2H), 3.76 (t, J = 5 Hz, 2H), 2.07 (s, 3H).
[2375] Example 30 (8)
[2376] 4- (2- (4-benzylpiperazin-1-yl) ethyl) oxy-1,1-dioxide benzo [b] thiophene
[2377]
[2378] TLC: Rf 0.57 (CHCl 3: MeOH = 5: 1);
[2379] _{NMR (CDCl 3): δ 7.58-7.38} (m, 2H), 7.38-7.18 (m, 6H), 7.05 (d, J = 8Hz, 1H), 6.60 (d, J = 7Hz, 1H), 4.35-4.05 (m, 2H), 3.52 (s, 2H), 2.85 (t, J = 6 Hz, 2H), 2.78-2.35 (m, 8H).
[2380] Example 30 (9)
[2381] Diethylcarbamoylmethyloxy-1,1-dioxide benzo [b] thiophene
[2382]
[2383] TLC: Rf 0.25 (hexane: AcOEt = 1: 2);
[2384] _{NMR (CDCl 3): δ 7.52} (d, J = 7.0Hz, 1H), 7.46 (t, J = 8.0Hz, 1H), 7.32 (d, J = 8.0Hz, 1H), 7.05 (d, J = 8.0 (Q, J = 7.2 Hz, 2H), 3.63 (q, J = 7.2 Hz, 2H), 1.23 t, J = 7.2 Hz, 3H), 1.15 (t, J = 7.2 Hz, 3H).
[2385] Example 30 (10)
[2386] 4-Cyanomethyloxy-1,1-dioxo [b] thiophene
[2387]
[2388] TLC: Rf 0.30 (hexane: AcOEt = 1: 1);
[2389] _{NMR (CDCl 3): δ 7.65-7.35} (m, 3H), 7.15 (d, J = 7.5Hz, 1H), 6.70 (d, J = 7.5Hz, 1H), 4.90 (s, 2H).
[2390] Example 30 (11)
[2391] 5- (Pyridin-3-yloxy) methyl-4-methoxy-1,1-dioxo [
[2392]
[2393] MS (APCI, Pos.): M / z 336 (M + MeOH + H) ⁺ , 304 (M + H) ⁺ .
[2394] Example 30 (12)
[2395] Nitro-1, 1-dioxo [b] thiophene (2-t-butoxycarbonylaminoethyl)
[2396]
[2397] TLC: Rf 0.32 (hexane: AcOEt = 1: 1);
[2398] _{NMR (CDCl 3): δ 7.80} (d, J = 8.6Hz, 1H), 7.33 (d, J = 7.0Hz, 1H), 7.18 (d, J = 8.6Hz, 1H), 6.93 (d, J = 7.0 (T, J = 5.2 Hz, 2H), 3.57 (q, J = 5.2 Hz, 2H), 1.45 (s, 9H).
[2399] Example 30 (13)
[2400] 5 - ((2E) -3-ethoxycarbonyl-2-propenyl) oxy-1,1-dioxide benzo [b] thiophene
[2401]
[2402] TLC: Rf 0.51 (hexane: AcOEt = 1: 1);
[2403] _{NMR (CDCl 3): δ 7.65} (d, J = 8.8Hz, 1H), 7.14 (d, J = 6.8Hz, 1H), 7.12-6.85 (m, 4H), 6.74 (d, J = 6.8Hz, 1H ), 6.23-6.10 (m, 1H), 4.82-4.73 (m, 2H), 4.23 (q, J = 7.0 Hz, 2H), 1.31 (t, J = 7.0 Hz, 3H).
[2404] Example 31
[2405] 4- (2,4-dimethoxyphenylmethyl) aminomethyl-1,1-dioxide benzo [b] thiophene
[2406]
[2407] (198 mg) was dissolved in acetonitrile (10 ml), 2,4-dimethoxybenzylamine hydrochloride (188 mg) and triethylamine (0.26 ml) in acetonitrile (6 ml), and the mixture was stirred at room temperature for 1 hour. Saturated sodium hydrogencarbonate was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate and concentrated. The residue was purified by silica gel column chromatography (ethyl acetate: hexane = 1: 1 -> 2: 1) to obtain the compound (113 mg) of the present invention having the following physical data.
[2408] TLC: Rf 0.29 (ethyl acetate);
[2409] _{NMR (CDCl 3): δ 7.63-7.39} (m, 4H), 7.07 (d, J = 8.0Hz, 1H), 6.66 (d, J = 7.0Hz, 1H), 6.49-6.39 (m, 2H), 3.83 (s, 2H), 3.81 (s, 3H), 3.79 (s, 3H), 3.72 (s, 2H), 1.98
[2410] Example 31 (1) to 31 (12)
[2411] 4-Bromomethyl-1,1-dioxide benzo [b] thiophene and 2,4-dimethoxybenzylamine hydrochloride were treated in the same manner as in Example 31 using the corresponding amine derivative, If necessary, converted into the corresponding salt by a known method to obtain the compound of the present invention shown below.
[2412] Example 31 (1)
[2413] 4- (pyridin-3-ylmethyl) aminomethyl-1,1-dioxide benzo [b] thiophene dihydrochloride
[2414]
[2415] TLC: Rf 0.37 (ethyl acetate: methanol = 5: 1);
[2416] _{NMR (CD 3 OD): δ} 9.11 (d, J = 1.7Hz, 1H), 8.92 (dd, J = 5.5, 1.7Hz, 1H), 8.73 (dt, J = 8.2, 1.7Hz, 1H), 8.10 ( J = 7.4 Hz, 1H), 7.18 (d, J = 8.2, 5.5 Hz, 1H), 7.94-7.90 (m, 2H), 7.84 J = 7.4 Hz, 1 H), 4.68 (s, 2H), 4.63 (s, 2H).
[2417] Example 31 (2)
[2418] 4- (2- (dimethylamino) ethyl) aminomethyl-1,1-dioxide benzo [b] thiophene
[2419]
[2420] MS (APCI, Pos.): M / z 299 (M + MeOH + H) ⁺ , 267 (M + H) ⁺ .
[2421] Example 31 (3)
[2422] 4- (N, N-bis (2-hydroxyethyl) amino) methyl-1,1-dioxide benzo [b] thiophene
[2423]
[2424] MS (APCI, Pos.): M / z 316 (M + MeOH + H) ⁺ , 284 (M + H) ⁺ .
[2425] Example 31 (4)
[2426] 4- (2- (2-hydroxyethoxy) ethyl) aminomethyl-1,1-dioxide benzo [b] thiophene
[2427]
[2428] MS (APCI, Pos.): M / z 599 (2M + MeOH + H) +, 567 (2M + H) +, 316 (m + MeOH + H) +, 284 (m + H) +.
[2429] Example 31 (5)
[2430] 4- (4-Benzylpiperazin-1-yl) methyl-1,1-dioxo [b] thiophene
[2431]
[2432] Free body:
[2433] TLC: Rf 0.27 (ethyl acetate: hexane = 1: 1);
[2434] _{NMR (CDCl 3): δ 7.71} (d, J = 7.0Hz, 1H), 7.62 (t, J = 4.6Hz, 1H), 7.44 (d, J = 4.6Hz, 2H), 7.35-7.25 (m, 5H ), 6.68 (d, J = 7.0 Hz, 1H), 3.60 (s, 2H), 3.51 (s, 2H), 2.46 (brs, 8H).
[2435] Dihydrochloride:
[2436] TLC: Rf 0.32 (ethyl acetate);
[2437] _{NMR (CD 3 OD): δ} 7.86 (d, J = 7.2Hz, 1H), 7.76-7.70 (m, 2H), 7.63 (d, J = 7.8Hz, 1H), 7.58-7.47 (m, 5H), 2H), 4.13 (s, 2H), 3.41 (br, 4H), 3.13 (br, 4H).
[2438] Example 31 (6)
[2439] Yl) methyl-l, l-dioxide &lt; / RTI &gt; benzo [b] thiophene
[2440]
[2441] MS (APCI, Pos.): M / z 374 (M + MeOH + H) ⁺ , 342 (M + H) ⁺ .
[2442] Example 31 (7)
[2443] 4- (4-ethoxycarbonylpiperazin-1-yl) methyl-1,1-dioxo [b] thiophene
[2444]
[2445] MS (APCI, Pos.): M / z 369 (M + MeOH + H) ⁺ , 337 (M + H) ⁺ .
[2446] Example 31 (8)
[2447] Yl) methyl-1,1-dioxo [b] thiophene [b] thiophene
[2448]
[2449] MS (APCI, Pos.): M / z 649 (2M + MeOH + H) +, 617 (2M + H) +, 341 (M + MeOH + H) +, 309 (M + H) +.
[2450] Example 31 (9)
[2451] 4-yl) piperazin-1-yl) methyl-1, 1 -dioxidobenzo [b] thiophene
[2452]
[2453] MS (APCI, Pos.): M / z 374 (M + MeOH + H) ⁺ , 342 (M + H) ⁺ .
[2454] Example 31 (10)
[2455] 4-Benzylaminomethyl-l, l-dioxide &lt; / RTI &gt; benzo [b] thiophene
[2456]
[2457] Free body:
[2458] TLC: Rf 0.66 (ethyl acetate);
[2459] _{NMR (CDCl 3): δ 7.62} (d, J = 7.2Hz, 1H), 7.56 (d, J = 7.5Hz, 1H), 7.52 (d, J = 7.5Hz, 1H), 7.46 (t, J = 7.5 1H), 7.39-7.24 (m, 5H), 6.69 (d, J = 7.2 Hz, 1H), 3.89 (s, 2H), 3.81 (s, 2H), 1.59
[2460] Hydrochloride:
[2461] TLC: Rf 0.47 (AcOEt: hexane = 2: 1);
[2462] _{NMR (CD 3 OD): δ} 7.95-7.18 (m, 8H), 7.15 (d, J = 7Hz, 1H), 6.98 (d, J = 7Hz, 1H), 4.48 (s, 2H), 4.36 (s, 2H).
[2463] Example 31 (11)
[2464] 4- (l-benzylpiperidin-4-yl) aminomethyl-l, l-dioxide &lt;
[2465]
[2466] Free body:
[2467] TLC: Rf 0.27 (ethyl acetate: methanol = 4: 1);
[2468] _{NMR (CDCl 3): δ 7.65} (d, J = 7.0Hz, 1H), 7.61 (d, J = 6.8Hz, 1H), 7.56-7.40 (m, 2H), 7.34-7.22 (m, 5H), 6.68 2H), 2.91-2.77 (m, 2H), 2.60-2.43 (m, 1H), 2.12-1.95 (m, 2H, ), 1.95-1.80 (m, 2H), 1.60-1.32 (m, 3H).
[2469] Dihydrochloride:
[2470] TLC: Rf 0.30 (ethyl acetate: methanol: triethylamine = 8: 1.5: 0.5);
[2471] _{NMR (DMSO-d 6 + CD} 3 OD): δ 7.97 (d, J = 7.2Hz, 1H), 7.95 (d, J = 7.8Hz, 1H), 7.88 (d, J = 7.5Hz, 1H), 7.65 2H), 2.50 (m, 3H), 2.50 (m, 2H), 2.50 -2.35 (m, 2 H), 2.35 - 2.05 (m, 2 H).
[2472] Example 31 (12)
[2473] 4- (morpholin-4-yl) methyl-1,1-dioxo [b] thiophene
[2474]
[2475] TLC: Rf 0.31 (ethyl acetate: methylene chloride = 1: 1);
[2476] _{NMR (CDCl 3): δ 7.69} (d, J = 7.2Hz, 1H), 7.64 (t, J = 4.8Hz, 1H), 7.46 (d, J = 4.8Hz, 2H), 6.71 (d, J = 7.2 Hz, 1H), 3.68 (t, J = 4.5 Hz, 4H), 3.60 (s, 2H), 2.44 (t, J = 4.5 Hz, 4H).
[2477] Example 32
[2478] 4-ethoxycarbonyl-l, l-dioxide benzo [b] thiophene
[2479]
[2480] 4-carboxy-1,1-dioxide benzo [b] thiophene (2.42 g) was dissolved in dimethylformamide (50 ml), potassium carbonate (3.10 g) and bromoethane (44.3 g) And stirred overnight. Water was added to the reaction mixture and extracted with ethyl acetate. The extract was washed successively with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated to obtain the compound (2.08 g) of the present invention having the following physical data.
[2481] TLC: Rf 0.24 (ethyl acetate: hexane = 1: 4);
[2482] _{NMR (CDCl 3): δ 8.25} (d, J = 7.4Hz, 1H), 8.20 (d, J = 7.8Hz, 1H), 7.88 (d, J = 7.8Hz, 1H), 7.61 (t, J = 7.8 Hz, 1H), 6.84 (d, J = 7.4 Hz, 1H), 4.44 (q, J = 7.2 Hz, 2H), 1.44 (t, J = 7.2 Hz, 3H).
[2483] Example 32 (1)
[2484] 4-Benzyloxycarbonyl-1,1-dioxo [b] thiophene
[2485]
[2486] Benzo [b] thiophene and benzoyl bromide in place of 4-carboxy-1,1-dioxide benzo [b] thiophene and bromoethane, the compound of the present invention having the following physical data was obtained.
[2487] MS (APCI, Pos.): M / z 301 (M + H) &lt; ⁺ & gt ^; .
[2488] Example 33
[2489] 4- (Pyridin-3-yl) -1,1-dioxo [b] thiophene
[2490]
[2491] (3-pyridyl) borane (440 mg), tripotassium phosphate (637 mg) was added to a dimethylformamide (5.0 ml) solution of 4-bromo-1,1-dioxide benzo [b] thiophene ) And tetrakis (triphenylphosphine) palladium (0) (116 mg) were added thereto, followed by stirring at 80 ° C for 2 hours. Water was added to the reaction mixture and extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was purified by silica gel column chromatography (chloroform: methanol = 50: 1) to obtain the compound (490 mg) of the present invention having the following physical data.
[2492] TLC: Rf 0.59 (CHCl 3: MeOH = 9: 1);
[2493] MS (APCI, Pos.): M / z 276 (M + MeOH + H) ⁺ , 244 (M + H) ⁺ .
[2494] Example 33 (1)
[2495] 6- (Pyridin-3-yl) -1,1-dioxo [b] thiophene
[2496]
[2497] Example 33 (4-Bromo-1, 1 -dioxo) benzo [b] thiophene was prepared using 6-bromo- , The compound of the present invention having the following physical properties was obtained.
[2498] MS (APCI, Pos.): M / z 276 (M + MeOH + H) ⁺ , 244 (M + H) ⁺ .
[2499] Example 34
[2500] 4- (4,4-dimethyl-4,5-dihydrooxazol-2-yl) -1,1-dioxide benzo [b] thiophene
[2501]
[2502] Thionyl chloride (2.1 ml) was added to the compound (519 mg) prepared in the following Example 72, and the mixture was stirred at room temperature for 1 hour. Ethyl acetate was added to the reaction mixture, and an aqueous 1N sodium hydroxide solution was added to the reaction mixture to obtain an alkali, followed by extraction with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous sodium sulfate and concentrated to obtain the compound (392 mg) of the present invention having the following physical data.
[2503] TLC: Rf 0.42 (ethyl acetate: hexane = 1: 1);
[2504] _{NMR (CDCl 3): δ 8.43} (d, J = 7.0Hz, 1H), 8.08 (d, J = 7.8Hz, 1H), 7.78 (d, J = 7.8Hz, 1H), 7.56 (t, J = 7.8 Hz, 1H), 6.76 (d, J = 7.0 Hz, 1H), 4.13 (s, 2H), 1.40 (s, 6H).
[2505] Examples 35 to 35 (68)
[2506] (33), Example 29, Examples 30 to 30 (13), Examples 31 to 31 (12) and Example (5) instead of 5-methyl-1,1- The procedure of Example 27 was repeated, except that the compounds prepared in Examples 32 to 32 (1), Examples 33 to 33 (1) and Example 34 or the corresponding derivatives were used, and if necessary, To obtain the compound of the present invention having the following physical properties.
[2507] Example 35
[2508] 3-ylmethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2509]
[2510] Free body:
[2511] TLC: Rf 0.44 (methylene chloride: methanol = 10: 1);
[2512] _{NMR (DMSO-d 6):} δ 9.41 (t, J = 5.7Hz, 1H), 8.67 (d, J = 1.8Hz, 1H), 8.46 (. Dd J = 4.8, 1.8Hz, 1H), 8.06 (d J = 6.9 Hz, 1H), 7.90-7.67 (m, 5H), 7.66-7.58 (m, 2H), 7.36 (dd, J = 8.1, 5.1 Hz, J = 6.9 Hz, 1H), 4.54 (d, J = 5.7 Hz, 2H), 4.10 (dd, J = 15.6, 9.3 Hz, 1H), 3.98 Hz, 1H).
[2513] Hydrochloride:
[2514] TLC: Rf 0.45 (CHCl 3: MeOH = 9: 1);
[2515] _{NMR (DMSO-d 6):} δ 9.70-9.62 (br, 1H), 8.95 (s, 1H), 8.75 (d, J = 5.4Hz, 1H), 8.55 (d, J = 7.5Hz, 1H), 8.13 (d, J = 7.5 Hz, 1H), 7.98 (d, J = 6.9 Hz, 1H), 7.94 (d, J = 7.5 Hz, 1H), 7.91-7.85 (Dd, J = 15.6, 5.1 Hz, 1H), 7.67-7.58 (m, 4H), 6.21 ), 4.07 (dd, J = 15.0, 9.0 Hz, 1H), 3.93 (d, J = 15.0 Hz, 1H).
[2516] Example 35 (1)
[2517] 4-benzylpiperazin-1-yl) carbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene hydrochloride
[2518]
[2519] TLC: Rf 0.46 (CHCl 3: MeOH = 19: 1);
[2520] _{NMR (DMSO-d 6):} δ 11.60-11.40 and 11.40 to 11.20 (each br, total 1H), 8.05-7.52 (m, 10H ), 7.51-7.23 (m, 3H), 5.88 and 5.81 (each d, J = 9.3 Hz, total 1H), 4.80-3.85 (m, 6H), 3.70-2.78 (m, 6H).
[2521] Example 35 (2)
[2522] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene · Hydrochloride
[2523]
[2524] TLC: Rf 0.27 (CHCl 3: MeOH = 19: 1);
[2525] _{NMR (DMSO-d 6):} δ 8.96 and 8.81 (each s, total 1H), 8.75 and 8.73 (each d, J = 5.4Hz, total 1H), 8.55 and 8.32 (each d, J = 7.5Hz, total 1H ), 7.95-7.62 (m, 9H), 5.81 and 5.79 (d, J = 8.4 Hz, total 1H), 4.15-3.84 and 3.73-3.62 (m, total 4H), 3.50-3.05 , 3.16 and 3.13 (s, total 3H, respectively).
[2526] Example 35 (3)
[2527] Carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2528]
[2529] TLC: Rf 0.55 (methylene chloride: methanol = 9: 1);
[2530] _{NMR (DMSO-d 6):} δ 8.84 (t, J = 5.4Hz, 1H), 7.98-7.90 (m, 2H), 7.84 (d, J = 7.5Hz, 1H), 7.81-7.73 (m, 3H) , 7.69-7.60 (m, 2H), 6.36 (d, J = 8.9 Hz, 1H), 4.58 (t, J = 5.1 Hz, 1H), 4.09 (dd, J = 15.3, 8.9 Hz, 1H) (d, J = 15.3 Hz, 1H), 3.67-3.53 (m, 2H), 3.53-3.35 (m, 6H).
[2531] Example 35 (4)
[2532] Carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2533]
[2534] TLC: Rf 0.48 (methylene chloride: methanol = 95: 5);
[2535] _{NMR (DMSO-d 6):} δ 9.04 (t, J = 5Hz, 1H), 8.03 (d, J = 7.2Hz, 1H), 7.92 (d, J = 7.2Hz, 1H), 7.90-7.70 (m, J = 8.4 Hz, 1H), 6.57 (d, J = 2.4 Hz, 1H), 6.47 (dd, J = 8.4, 2.4 Hz, 1H) J = 15, 5 Hz, 1H), 4.27 (d, J = 8.5 Hz, 1H), 4.47 (dd, J = Hz, 1H), 3.97 (d, J = 15 Hz, 1H), 3.83 (s, 3H), 3.74 (s, 3H).
[2536] Example 35 (5)
[2537] 4-yl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2538]
[2539] Free body:
[2540] TLC: Rf 0.30 (methylene chloride: methanol = 9: 1);
[2541] NMR (CDCl ₃ + CD ₃ OD): δ 8.00-7.50 (m, 8H), 7.45-7.20 (m, 5H), 6.25 (dd, J = 7.5, 2.5 Hz, 1H), 4.10-3.90 2H), 3.10-2.90 (m, 2H), 2.30-1.95 (m, 4H), 3.80 (dd, J = 1.90-1.70 (m, 2H).
[2542] Hydrochloride:
[2543] TLC: Rf 0.40 (methanol: ethyl acetate = 1: 10);
[2544] _{NMR (CD 3 OD): δ} 8.04-7.43 (m, 13H), 6.15 (dd, J = 8.2Hz, 2.6Hz, 1H), 4.35 (s, 2H), 4.34-4.06 (m, 1H), 3.94 ( dd, J = 15.2 Hz, 8.2 Hz, 1H), 3.83 (dd, J = 15.2 Hz, 2.6 Hz, 1H), 3.74-3.08 (m, 4H), 2.56-1.56 (m, 4H).
[2545] Methanesulfonate:
[2546] TLC: Rf 0.40 (methanol: ethyl acetate = 1: 10);
[2547] _{NMR (CD 3 OD): δ} 8.06-7.44 (m, 13H), 6.14 (dd, J = 8.2Hz, 2.6Hz, 1H), 4.34 (s, 2H), 4.32-4.12 (m, 1H), 4.01- 3.77 (m, 2H), 3.68-3.08 (m, 4H), 2.69 (s, 3H), 2.54 - 1.74 (m, 4H).
[2548] Example 35 (6)
[2549] 4-ylmethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2550]
[2551] TLC: Rf 0.35 (CHCl 3: MeOH = 9: 1);
[2552] _{NMR (DMSO-d 6):} δ 9.45 (. T J = 7Hz, 1H), 8.50 (d, J = 8Hz, 2H), 8.10 (d, J = 8Hz, 1H), 8.00 (d, J = 8Hz, J = 8 Hz, 1H), 7.90 (t, J = 8 Hz, 1H), 7.80-7.55 (m, 5H), 7.45 , 2H), 4.10 (dd, J = 7 Hz and 15 Hz, 1H), 4.00 (dd, J = 1 Hz and 15 Hz, 1H).
[2553] Example 35 (7)
[2554] Carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2555]
[2556] TLC: Rf 0.37 (AcOEt: hexane = 3: 2);
[2557] _{NMR (DMSO-d 6):} δ 8.90 (t, J = 7Hz, 1H), 8.00-7.55 (m, 8H), 6.25 (dd, J = 1Hz and 7Hz, 1H), 4.10 (dd , J = 7Hz and 1H), 3.95 (dd, J = 1 Hz and 15 Hz, 1H), 3.45 (m, 2H), 2.60 (t, J = 7 Hz, 2H).
[2558] Example 35 (8)
[2559] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2560]
[2561] TLC: Rf 0.67 (CHCl 3: MeOH = 4: 1);
[2562] _{NMR (DMSO-d 6):} δ 9.40 (t, J = 7Hz, 1H), 8.00-7.60 (m, 8H), 7.40 (d, J = 6Hz, 1H), 7.10 (d, J = 4Hz, 1H) J = 7 Hz and 16 Hz, 1H), 4.75 (dd, J = 7 Hz and 6 Hz, 1H), 6.30 (dd, J = 4.10 (dd, J = 7 Hz and 12 Hz, 1H), 4.00 (dd, J = 1 Hz and 12 Hz, 1H).
[2563] Example 35 (9)
[2564] Benzylcarbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxo [b] thiophene
[2565]
[2566] TLC: Rf 0.58 (methylene chloride: methanol = 10: 1);
[2567] _{NMR (CDCl 3 + DMSO-d} 6): δ 8.74 (t, J = 5.7Hz, 1H), 8.03 (dd, J = 7.8, 0.9Hz, 1H), 7.93-7.80 (m, 3H), 7.78-7.68 (m, 2H), 7.59 (t, J = 7.8 Hz, 2H), 7.50 (d, J = 6.9 Hz, 2H), 7.39-7. J = 15.0 Hz, 1H), 4.69 (dd, J = 14.9, 5.7 Hz, 1H), 4.62 Hz, 1H).
[2568] Example 35 (10)
[2569] 2-ylmethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2570]
[2571] TLC: Rf 0.56 (methylene chloride: methanol = 10: 1);
[2572] _{NMR (DMSO-d 6):} δ 9.42 (t, J = 6.3Hz, 1H), 8.54 (d, J = 5.1Hz, 1H), 8.11 (d, J = 7.5Hz, 1H), 7.97 (d, J J = 8.1 Hz, 1H), 7.95-7.82 (m, 1H), 7.80-7.70 (m, 4H), 7.62 J = 16.0, 4.8 Hz, 1 H), 4.54 (dd, J = 16.0, 4.8 Hz, 1 H), 4.10 (d, J = dd, J = 15.6, 4.8 Hz, 1H), 4.00 (d, J = 15.6, 9.3 Hz, 1H).
[2573] Example 35 (11)
[2574] Yl) ethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2575]
[2576] Free body:
[2577] TLC: Rf 0.10 (methylene chloride: methanol = 10: 1);
[2578] _{NMR (CDCl 3): δ 7.90-7.78} (m, 4H), 7.75-7.64 (m, 2H), 7.62-7.51 (m, 2H), 7.42 (bs, 1H), 6.29 (d, J = 8.1Hz, 1H), 3.84 (dd, J = 15.0,1.5 Hz, 1H), 3.75-3.60 (m, 2H), 3.58-3.45 (m, 1H), 2.77-2.60 4H), 1.80-1.40 (m, 6H).
[2579] Hydrochloride:
[2580] TLC: Rf 0.30 (ethyl acetate: methanol: triethylamine = 8: 1.5: 0.5);
[2581] _{NMR (DMSO-d 6):} δ 10.25 (. Br s, 1H), 9.32 (t, J = 5.4Hz, 1H), 8.10 (dd, J = 7, 1.4Hz, 1H), 8.00-7.80 (m, J = 8.8 Hz, 1H), 3.97 (d, J = 8 Hz, 2H), 7.80-7.70 (m, 3H), 7.70-7.55 2H), 3.70-3.50 (m, 2H), 3.50-3.10 (m, 3H), 3.10-2.80 (m, 2H), 2.00-1.60 , 1.60-1.20 (m, 1H).
[2582] Methanesulfonate:
[2583] TLC: Rf 0.30 (ethyl acetate: methanol: triethylamine = 8: 1.5: 0.5);
[2584] _{NMR (DMSO-d 6):} δ 9.13 (t, J = 5Hz, 1H), 9.00 (. Br s, 1H), 8.05 (dd, J = 7, 1.4Hz, 1H), 8.00-7.80 (m, 2H ), 7.80-7.70 (m, 3H), 7.70-7.55 (m, 2H), 6.28 (d, J = 8.2 Hz, 1H), 4.12 (dd, J = 16, 8.2 Hz, 1H) (M, 2H), 3.10-2.90 (m, 2H), 2.00-1.60 (m, 4H), 1.60-1.30 ).
[2585] Example 35 (12a)
[2586] 2-methylpropyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2587]
[2588] TLC: Rf 0.34 (hexane: AcOEt = 1: 1);
[2589] _{NMR (CDCl 3): δ 7.99} (dd, J = 7.5, 0.9Hz, 1H), 7.87-7.84 (m, 3H), 7.75 (t, J = 7.5Hz, 1H), 7.72-7.67 (m, 1H) J = 8.8 Hz, 1H), 7.60-7.55 (m, 2H), 6.80 (d, J = 8.8 Hz, (d, J = 15.0 Hz, 1H), 3.65 (dd, J = 15.0, 8.7 Hz, 1H), 2.47-2.41 (m, 1H), 1.54 , 3H), 1.06 (d, J = 7.0 Hz, 3H).
[2590] (The solid of the carbon atom to which the phenylsulfonyl group is bonded is not determined but is a single substance)
[2591] Example 35 (12b)
[2592] 2-methylpropyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2593]
[2594] TLC: Rf 0.34 (hexane: AcOEt = 1: 1);
[2595] _{NMR (CDCl 3): δ 7.98} (d, J = 7.8Hz, 0.5H), 7.91-7.80 (m, 3.5H), 7.76-7.67 (m, 2H), 7.60-7.55 (m, 2H), 6.92 ( (dd, J = 9.3, 1.5 Hz, 1H), 6.84 (d, J = 8.7 Hz, 0.5H), 6.25 J = 8.1, 5.3 Hz, 0.5H), 3.87 (dd, J = 15.0, 1.5 Hz, 0.5H), 3.80 (dd, J = (dd, J = 15.0, 1.5 Hz, 0.5H), 3.67 (dd, J = 15.0,9.3Hz, 0.5H), 2.41-2.36 (m, 0.5H), 2.33-2.24 (d, J = 6.9 Hz, 1.5H), 1.07 (d, J = 6.9 Hz, 1.5H), 1.06 (d, J = 6.9 Hz, 1.5H), 1.05 (d, J = 6.9 Hz, 1.5H).
[2596] Example 35 (13)
[2597] Carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2598]
[2599] TLC: Rf 0.60 (CHCl 3: MeOH = 9: 1);
[2600] _{NMR (DMSO-d 6):} δ 9.35 (t, J = 7Hz, 1H), 8.05 (d, J = 8Hz, 1H), 7.95 (d, J = 8Hz, 1H), 7.85 (t, J = 8Hz, J = 10 Hz, 1H), 4.60 (dd, J = 16 Hz and 7 Hz, 1H), 4.45 (dd, J = 16 Hz and 7 Hz, 1H), 4.10 (dd, J = 16 Hz and 10 Hz, 1H), 4.00 (d, J = 16 Hz, 1H).
[2601] Example 35 (14)
[2602] Carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2603]
[2604] TLC: Rf 0.60 (CHCl 3: MeOH = 9: 1);
[2605] _{NMR (DMSO-d 6):} δ 9.40 (t, J = 7Hz, 1H), 8.05 (d, J = 8Hz, 1H), 7.95 (d, J = 8Hz, 1H), 7.85 (t, J = 8Hz, 1H), 7.80-7.70 (m, 3H), 7.70-7.55 (m, 2H), 7.45-7. 20 (m, d, J = 7 Hz, 2H), 4.10 (dd, J = 16 Hz and 10 Hz, 1H), 3.97 (dd, J = 16 Hz, 1H).
[2606] Example 35 (15)
[2607] Carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2608]
[2609] TLC: Rf 0.69 (CHCl 3: MeOH = 9: 1);
[2610] _{NMR (DMSO-d 6):} δ 9.31 (t, J = 6.0Hz, 1H), 8.06 (d, J = 7.6Hz, 1H), 7.96 (d, J = 7.6Hz, 1H), 7.85 (t, J = 7.6 Hz, 1 H), 7.80-7.70 (m, 3H), 7.70-7.55 (m, 2H), 7.30-7.15 (m, 3H), 7.15-7.00 (Dd, J = 15 Hz and 8.6 Hz, 1H), 3.98 (dd, J = 15 Hz and 2.0 Hz, 1H), 2.27 (s, 3H).
[2611] Example 35 (16)
[2612] Carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2613]
[2614] TLC: Rf 0.70 (CHCl 3: MeOH = 9: 1);
[2615] _{NMR (DMSO-d 6):} δ 9.15 (t- type, J = 6Hz, 1H), 8.08 (d, J = 7.5Hz, 1H), 7.95 (d, J = 7.5Hz, 1H), 7.85 (t, 1H), 7.80-7.70 (m, 3H), 7.70-7.55 (m, 2H), 7.50-7.35 J = 16 Hz and 6 Hz, 1 H), 4.10 (dd, J = 15.5 Hz and 8 Hz, 2H), 6.28 (d, J = 8 Hz, , &Lt; / RTI &gt; 1H), 4.00 (d, J = 15.5 Hz, 1H), 3.85 (s, 3H).
[2616] Example 35 (17)
[2617] Carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2618]
[2619] TLC: Rf 0.52 (CHCl 3: MeOH = 9: 1);
[2620] _{NMR (DMSO-d 6):} δ 9.22 (t, J = 5.5Hz, 1H), 8.05 (d, J = 7.0Hz, 1H), 7.95 (d, J = 7.0Hz, 1H), 7.85 (t, J = 7.0 Hz, 1H), 7.80-7.70 (m, 3H), 7.70-7.57 (m, 2H), 7.15-6.90 (m, 3H), 6.29 (dd, J = 8.5 Hz and 2.0 Hz, J = 15.0 Hz and 5.5 Hz, 1H), 4.38 (dd, J = 15.0 Hz and 5.5 Hz, 1H), 4.11 (dd, J = 15.0 Hz and 5.5 Hz, 1H) 15.5 Hz and 2.0 Hz, IH), 3.82 (s, 6H).
[2621] Example 35 (18)
[2622] Carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2623]
[2624] TLC: Rf 0.48 (CHCl 3: MeOH = 9: 1);
[2625] _{NMR (DMSO-d 6):} δ 9.27 (t, J = 6.0Hz, 1H), 8.04 (d, J = 7.5Hz, 1H), 7.95 (d, J = 7.5Hz, 1H), 7.85 (t, J = 7.5 Hz, 1 H), 7.80-7.70 (m, 3H), 7.70-7.57 (m, 2H), 7.44 (s, (Dd, J = 15.0 Hz and 8.6 Hz, 1H), 3.99 (dd, J = 15.0 Hz and 1.4 Hz, 1H), 3.73 (s, 3H) 3.72 (s, 3 H).
[2626] Example 35 (19)
[2627] Carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2628]
[2629] TLC: Rf 0.59 (CHCl 3: MeOH = 9: 1);
[2630] _{NMR (DMSO-d 6):} δ 9.41 (t, J = 5.8Hz, 1H), 8.09 (dd, J = 7.6Hz and 1.5Hz, 1H), 7.98 (dd , J = 7.6Hz qnd 1.5Hz, 1H) , 7.87 (t, J = 7.6 Hz, 1H), 7.80-7.70 (m, 3H), 7.70-7.57 (m, 2H), 7.50-7.35 J = 15 Hz and 8.4 Hz, 1H), 4.54 (d, J = 5.8 Hz, 2H), 4.10 (dd, J = 15 Hz and 8.4 Hz, 1H).
[2631] Example 35 (20)
[2632] Carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2633]
[2634] TLC: Rf 0.58 (CHCl 3: MeOH = 9: 1);
[2635] _{NMR (DMSO-d 6):} δ 9.31 (m, 1H), 8.06 (d, J = 7.6Hz, 1H), 7.95 (d, J = 7.6Hz, 1H), 7.85 (t, J = 7.6Hz, 1H ), 7.80-7.70 (m, 3H), 7.70-7.55 (m, 2H), 6.79 (s, 2H), 6.32 (d, J = 8.4 Hz, (Dd, J = 15 Hz and 8.4 Hz, 1H), 3.99 (d, J = 15 Hz, 1H), 3.73 (s, 6H) , &Lt; / RTI &gt; 3.61 (s, 3H).
[2636] Example 35 (21)
[2637] Benzimidazol-2-ylmethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2638]
[2639] TLC: Rf 0.27 (CHCl 3: MeOH = 9: 1);
[2640] _{NMR (DMSO-d 6):} δ 12.23 (broad-s, 1H), 9.48 (m, 1H), 8.17 (d, J = 7Hz, 1H), 8.00-7.80 (m, 2H), 7.80-7.70 (m J = 8 Hz, 1H), 4.89 (dd, J = 16 Hz and 6 Hz, 1H), 4.51 (dd, J = 16 Hz and 5 Hz, 1H), 4.13 (dd, J = 15 Hz and 8 Hz, 1H), 3.99 (d, J = 15 Hz, 1H).
[2641] Example 35 (22)
[2642] Carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2643]
[2644] TLC: Rf 0.63 (CHCl 3: MeOH = 9: 1);
[2645] _{NMR (DMSO-d 6):} δ 9.44 (t, J = 5.6Hz, 1H), 8.11 (d, J = 7.4Hz, 1H), 7.98 (d, J = 7.4Hz, 1H), 7.88 (t, J = 7.4 Hz, 1 H), 7.80-7.70 (m, 3H), 7.70-7.55 (m, 2H), 7.30-7.00 (m, 3H), 6.29 (dd, J = 8.5 Hz and 2 Hz, m, 2H), 4.11 (dd, J = 15 Hz and 8.5 Hz, 1H), 3.98 (dd, J = 15 Hz and 2 Hz, 1H).
[2646] Example 35 (23)
[2647] Benzyl-N-methylcarbamoyl) -3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2648]
[2649] _{NMR (CDCl 3): δ 8.00-7.25} (m, 13H), 6.00-5.90 (m, 1H), 5.19 (d, J = 15Hz) and 5.03 (d, J = 18Hz, total of 1H), 4.49 (d, J = 15 Hz) and 4.40 (d, J = 18 Hz, total 1H), 3.75 (dd, J = 2 Hz and 15 Hz, 1H), 3.63 (dd, J = 8.5 Hz and 15 Hz, 1H), 3.18 and 3.12 , Total 3H).
[2650] Example 35 (24)
[2651] Carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2652]
[2653] TLC: Rf 0.50 (CHCl 3: MeOH = 9: 1);
[2654] _{NMR (DMSO-d 6):} δ 9.52 (m, 1H), 8.30-7.55 (m, 13H), 6.27 (d, J = 6.4Hz, 1H), 4.65 (m, 2H), 4.10 (dd, J = 15.5 Hz and 6.4 Hz, 1H), 3.97 (d, J = 15.5 Hz, 1H).
[2655] Example 35 (25)
[2656] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2657]
[2658] TLC: Rf 0.39 (ethyl acetate: methanol = 95: 5);
[2659] _{NMR (DMSO-d 6):} δ 8.79 (t, J = 5.7Hz, 1H), 8.18 (brs, 1H), 8.14 (d, J = 8.1Hz, 1H), 7.91 (d, J = 8.1Hz, 1H ), 7.82-7.75 (m, 3H), 7.68-7.58 (m, 2H), 5.83 (dd, J = 9.4 Hz, 3.0 Hz, 1H), 4.77 (t, J = 5.7 Hz, 1H) J = 15.0 Hz, 9.6 Hz, 1H), 3.84 (dd, J = 15.0 Hz, 3.0 Hz, 1H), 3.54 (q, J = 5.7 Hz, 2H) .
[2660] Example 35 (26)
[2661] Carbamoyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2662]
[2663] Free body:
[2664] TLC: Rf 0.32 (ethyl acetate: methanol = 9: 1);
[2665] _{NMR (CDCl 3): δ 8.59-8.56} (m, 2H), 8.04 (d, J = 8.5Hz, 1H), 7.74-7.68 (m, 3H), 7.58-7.53 (m, 1H), 7.47-7.31 ( J = 15.0, 6.0 Hz, 1H), 4.59 (dd, J = 15.0, 6.0 Hz, 1H), 4.11 (d, J = = 15.0 Hz, 1H), 3.77 (dd, J = 15.0, 8.5 Hz, 1H), 3.67 (s, 3H).
[2666] Hydrochloride:
[2667] TLC: Rf 0.32 (ethyl acetate: methanol = 9: 1);
[2668] _{NMR (DMSO-d 6):} δ 9.37 (t, J = 5.5Hz, 1H), 8.90 (s, 1H), 8.84 (d, J = 5.5Hz, 1H), 8.49 (d, J = 8.0Hz, 1H ), 8.02 (dd, J = 8.0,5.5 Hz, 1H), 7.85-7.75 (m, 4H), 7.67-7.56 (m, 3H), 5.70 (d, J = 9.0 Hz, 1H), 4.72-4.60 m, 2H), 4.15 (d, J = 15.0 Hz, 1H), 4.02 (dd, J = 15.0, 9.0 Hz, 1H), 3.56 (s, 3H).
[2669] Example 35 (27)
[2670] Carbamoyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2671]
[2672] Free body:
[2673] TLC: Rf 0.24 (ethyl acetate: methanol: triethylamine = 8: 1: 1);
[2674] _{NMR (CDCl 3): δ 8.00} (d, J = 8.0Hz, 1H), 7.76-7.73 (m, 2H), 7.67-7.61 (m, 1H), 7.51-7.41 (m, 3H), 7.32 (bt, J = 5.0 Hz, 1H), 5.23 (t, J = 9.0 Hz, 1H), 4.19 (d, J = 15.0 Hz, 1H), 3.81 (dd, J = 3H), 3.64-3.42 (m, 2H), 2.51 (t, J = 6.0 Hz, 1H), 2.28 (s, 6H).
[2675] Hydrochloride:
[2676] TLC: Rf 0.24 (ethyl acetate: methanol: triethylamine = 8: 1: 1);
[2677] _{NMR (DMSO-d 6):} δ 10.47 (br, 1H), 8.90 (t, J = 5.5Hz, 1H), 7.86-7.76 (m, 4H), 7.69-7.64 (m, 2H), 7.56 (d, J = 8.0 Hz, 1H), 5.69 (d, J = 8.5 Hz, 1H), 4.13 (d, J = 15.0 Hz, 1H), 4.00 m, 2H), 3.63 (s, 3H), 3.25 (t, J = 6.0 Hz, 2H), 2.82 (s, 6H).
[2678] Example 35 (28)
[2679] 5-dimethylcarbamoyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2680]
[2681] TLC: Rf 0.35 (ethyl acetate);
[2682] _{NMR (DMSO-d 6):} δ 7.83 (d, J = 8.0Hz, 2H), 7.44 (t, J = 7.5Hz, 1H), 7.63 (dd, J = 8.0Hz, 7.5Hz, 2H), 7.49 ( J = 8.5 Hz, 1H), 4.13 (d, J = 14.5 Hz, 1H), 4.02 (dd, J = J = 14.5 Hz, 8.5 Hz, 1H), 3.59 (s, 3H), 3.01 (s, 3H), 2.78 (s, 3H).
[2683] Example 35 (29)
[2684] (2,3,4,5,6,7-hexahydro-1H-azepin-1-yl) carbonyl-4-methoxy-3-phenylsulfonyl- 1-dioxide benzo [b] thiophene
[2685]
[2686] TLC: Rf 0.21 (ethyl acetate: hexane = 2: 1);
[2687] _{NMR (DMSO-d 6):} δ 7.87-7.70 (m, 3H), 7.70-7.60 (m, 2H), 7.60-7.53 (m, 2H), 5.67 (d, J = 8.7Hz, 1H), 4.26 ( (d, J = 15.0 Hz, 1H), 4.05 (dd, J = 15.0, 8.7 Hz, 1H), 3.70-3.54 (m, 2H), 3.48 -1.40 (m, 8H).
[2688] Example 35 (30)
[2689] Benzo [b] thiophene &lt; RTI ID = 0.0 &gt; (5-methoxyphenylsulfonyl) -2,3-dihydro-
[2690]
[2691] TLC: Rf 0.54 (ethyl acetate: hexane = 2: 1);
[2692] _{NMR (DMSO-d 6):} δ 8.13 (d, J = 7.8Hz, 1H), 7.87 (d, J = 7.5Hz, 1H), 7.83-7.70 (m, 2H), 7.70-7.56 (m, 2H) , 7.66 (t, J = 7.8 Hz, 2H), 7.31 (d, J = 7.5 Hz, 1H), 7.25 (d, J = 8.7 Hz, 1H), 4.39-3.97 (m, 2H), 3.76 (dd, J = 18.6, 8.7 Hz, 1H), 3.70-3.50 3.21-3.08 (m, 2H).
[2693] Example 35 (31)
[2694] Yl) carbonyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2695]
[2696] TLC: Rf 0.78 (methylene chloride: methanol = 10: 1);
[2697] _{NMR (CDCl 3 + DMSO-d} 6): δ 7.94-7.86 (m, 1H), 7.77-7.66 (m, 2H), 7.64-7.50 (m, 4H), 7.44-7.16 (m, 2H), 7.10- (M, 2H), 3.50-2.80 (m, 2H), 3.99-3.65 (m, , 6H).
[2698] Example 35 (32)
[2699] 1-yl) carbonyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1- Dioxo [b] thiophene
[2700]
[2701] TLC: Rf 0.51 (methylene chloride: methanol = 10: 1);
[2702] _{NMR (CDCl 3): δ 7.93-7.86} (m, 1H), 7.74-7.43 (m, 7H), 7.40-7.30 (m, 3H), 5.31-5.20 (m, 1H), 4.24-3.64 (m, 7H ), 3.34-3.10 (m, 2H), 3.06-2.90 (m, 2H), 2.70-2.30 (m, 6H).
[2703] Example 35 (33)
[2704] 3-ylcarbonyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2705]
[2706] Free body:
[2707] TLC: Rf 0.38 (ethyl acetate: methanol = 9: 1);
[2708] _{NMR (DMSO-d 6):} δ 9.31 (t, J = 6.0Hz, 1H), 9.05 (d, J = 1.5Hz, 1H), 8.72 (dd, J = 5.0, 1.5Hz, 1H), 8.23 (dt J = 8.0, 5.0 Hz, 1H), 6.05 (d, J = 8.5 Hz, 1H), 5.01 (dd, J = 16.0, 6.0 Hz, 1H), 4.78 (dd, J = 16.0, 6.0 Hz, 1H), 4.02 (dd, J = 15.3, 8.5 Hz, 1H), 3.86 (d, J = 15.3 Hz, 1H).
[2709] Hydrochloride:
[2710] TLC: Rf 0.38 (ethyl acetate: methanol = 9: 1);
[2711] _{NMR (DMSO-d 6):} δ 9.63-9.59 (m, 1H), 9.20 (s, 1H), 8.86 (d, J = 5.0Hz, 1H), 8.57-8.54 (m, 1H), 7.87-7.63 ( J = 15.8, 5.7 Hz, 1H), 4.00 (dd, J = 8.5 Hz, 1H), 6.01 (dd, J = = 15.5, 8.5 Hz, 1H), 3.86 (d, J = 15.5 Hz, 1H).
[2712] Example 35 (34)
[2713] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2714]
[2715] TLC: Rf 0.20 (ethyl acetate: hexane = 1: 1);
[2716] _{NMR (CDCl 3): δ 7.75-7.35} (m, 6H), 7.24 (d, J = 8Hz, 1H), 6.93 (d, J = 8Hz, 1H), 6.68 (t, J = 2Hz, 2H), 6.15 2H), 5.21 (d, J = 9 Hz, 1H), 4.53-4.00 (m, 2H), 4.10 (d, J = 15 Hz, 1H), 4.00-3.65 3.73 (dd, J = 9,15 Hz, 1H), 2.19 (quintet, J = 5 Hz, 2H).
[2717] Example 35 (35)
[2718] 2-ylmethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2719]
[2720] Free body:
[2721] TLC: Rf 0.21 (benzene: ethyl acetate = 2: 1);
[2722] _{NMR (CDCl 3): δ 8.42} (d, J = 9Hz, 1H), 8.03 (d, J = 8Hz, 2H), 7.90-7.20 (m, 11H), 5.80 (d, J = 8Hz, 1H), 5.31 (d, J = 13 Hz, 1H), 5.09 (d, J = 13 Hz, 1H), 4.24 (d, J = 15 Hz, 1H), 4.02 (dd, J = 8, 15 Hz, 1H).
[2723] Hydrochloride:
[2724] TLC: Rf 0.30 (hexane: AcOEt = 1: 2);
[2725] _{NMR (DMSO-d 6):} δ 8.64 (d, J = 8.5Hz, 1H), 8.20 (d, J = 8.5Hz, 1H), 8.13 (d, J = 8.5Hz, 1H), 7.92 (t- type J = 8.5 Hz, 1H), 7.81-7.65 (m, 5H), 7.48-7.31 (m, 5H), 5.91 (d, , 5.21 (d, J = 13.5 Hz, 1H), 4.22 (d, J = 15.0 Hz, 1H), 4.02 (dd, J = 9.0 Hz, 1H).
[2726] Example 35 (36)
[2727] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene A solution of 4- (2- (pyrrol-
[2728]
[2729] TLC: Rf 0.36 (hexane: AcOEt = 1: 2);
[2730] _{NMR (CDCl 3 + CD 3 OD} ): δ 7.85-7.58 (m, 3H), 7.58-7.42 (m, 3H), 7.28 (d, J = 8Hz, 1H), 6.92 (d, J = 8Hz, 1H) , 6.74 (t, J = 2 Hz, 2H), 6.18 (t, J = 2 Hz, 2H), 5.16 (d, J = 9 Hz, 1H), 4.30-4.05 , 15 Hz, 1H).
[2731] Example 35 (37)
[2732] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene hydrochloride
[2733]
[2734] TLC: Rf 0.25 (ethyl acetate);
[2735] _{NMR (CD 3 OD): δ} 9.88 (s, 1H), 7.80-7.40 (m, 6H), 7.26 (d, J = 8Hz, 1H), 7.25 (d, J = 8Hz, 1H), 5.48 (d, J = 9 Hz, 1H), 3.42-3.15 (m, 2H), 4.08 (d, J = , &Lt; / RTI &gt; 2.60 (s, 3H).
[2736] Example 35 (38)
[2737] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2738]
[2739] Free body:
[2740] TLC: Rf 0.26 (ethyl acetate: methanol = 10: 1);
[2741] _{NMR (CDCl 3): δ 8.53} (dd, J = 1, 5Hz, 2H), 7.78-7.35 (. M 6H), 7.25 (d, J = 7Hz, 1H), 7.17 (d, J = 6Hz, 2H) , 6.95 (d, J = 8 Hz, 1H), 5.17 (d, J = 9 Hz, 1H), 4.14 (d, J = 15 Hz, 1H), 4.05-3.82 , 15 Hz, 1H), 2.87 (t, J = 6 Hz, 2H), 2.10 (quintet, J = 6 Hz, 2H).
[2742] Hydrochloride:
[2743] TLC: Rf 0.39 (ethyl acetate: methanol: aqueous ammonia = 100: 10: 1);
[2744] _{NMR (DMSO-d 6):} δ 8.83 (d, J = 6Hz, 2H), 7.90 (d, J = 5Hz, 2H), 7.85-7.52 (m, 6H), 7.34 (d, J = 8Hz, 1H) , 7.24 (d, J = 8 Hz, 1H), 5.64 (d, J = 9 Hz, 1H), 4.18 (m, 2 H), 2.10-1.60 (m, 2 H).
[2745] Example 35 (39)
[2746] 3-ylmethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2747]
[2748] TLC: Rf 0.23 (hexane: AcOEt = 1: 1);
[2749] NMR (CD ₃ OD): 7.95-7.45 (m, 6H), 7.40-7.05 (m, 2H), 5.53 (d, J = 9 Hz, 1H) dd, J = 9, 15 Hz, 1H), 4.05-3.55 (m, 4H), 3.20-2.40 (m, 2H), 2.00-1.20 (m, 5H), 1.47 and 1.44 (s, 9H respectively).
[2750] Example 35 (40)
[2751] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2752]
[2753] Free body:
[2754] TLC: Rf 0.17 (CHCl 3: MeOH = 10: 1);
[2755] _{NMR (CDCl 3): δ 7.85-7.68} (m, 2H), 7.68-7.35 (m, 4H), 7.28 (d, J = 8Hz, 1H), 6.97 (d, J = 8Hz, 1H), 5.30 (d J = 9 Hz, 1H), 4.23 (d, J = 15 Hz, 1H), 4.15-3.95 (m, 1H), 3.95-3.70 2.78 (t, J = 6 Hz, 2H), 2.70-2. 45 (m, 4H), 1.95-1.60 (m, 4H).
[2756] Hydrochloride:
[2757] TLC: Rf 0.36 (ethyl acetate: acetic acid: water = 3: 1: 1);
[2758] _{NMR (CDCl 3 + CD 3 OD} ): δ 7.98-7.82 (m, 2H), 7.80-7.45 (m, 4H), 7.34 (d, J = 8Hz, 1H), 7.26 (d, J = 8Hz, 1H) , 6.20-6.05 (m, 1H), 4.75-4.50 (m, 1H), 4.50-4.25 (m, 1H), 4.10-3.85 (m, 2H), 3.85-3.45 m, 2H), 2.40-2.00 (m, 4H).
[2759] Example 35 (41)
[2760] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2761]
[2762] Free body:
[2763] TLC: Rf 0.24 (CHCl 3: MeOH = 10: 1);
[2764] _{NMR (CDCl 3): δ 7.85-7.67} (m, 2H), 7.67-7.36 (m, 4H), 7.27 (d, J = 8Hz, 1H), 6.97 (d, J = 8Hz, 1H), 5.29 (d J = 9 Hz, 1H), 4.25 (d, J = 15 Hz, 1H), 4.18-3.92 (m, 1H), 3.92-3.65 2.62 (t, J = 6 Hz, 2H), 2.46 (t, J = 6 Hz, 4H), 1.90 - 1.35 (m, 6H).
[2765] Hydrochloride:
[2766] TLC: Rf 0.40 (ethyl acetate: acetic acid: water = 3: 1: 1);
[2767] _{NMR (CDCl 3 + CD 3 OD} ): δ 7.95-7.75 (m, 2H), 7.75-7.45 (m, 4H), 7.32 (d, J = 8Hz, 1H), 7.30 (d, J = 8Hz, 1H) , 6.05-5.85 (m, 1H), 4.75-4.38 (m, 2H), 3.95-3.42 (m, 6H), 3.15-2.85 (m, 2H), 2.35-1.35 (m, 6H).
[2768] Example 35 (42)
[2769] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2770]
[2771] TLC: Rf 0.17 (ethyl acetate: hexane = 2: 1);
[2772] _{NMR (CDCl 3): δ 7.82-7.70} (m, 2H), 7.65-7.35 (m, 4H), 7.27 (d, J = 8Hz, 1H), 7.00 (d, J = 8Hz, 1H), 5.30 (d 1H), 4.32-4.05 (m, 4H), 4.05-3.88 (m, 1H), 3.84-3.75 (m, 5H), 2.05 (s, 3H).
[2773] Example 35 (43)
[2774] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene (4-benzylpiperazin-
[2775]
[2776] Free body:
[2777] TLC: Rf 0.42 (CHCl 3: MeOH = 5: 1);
[2778] NMR (CDCl ₃ ): 7.80-7.68 (m, 2H), 7.68-7.37 (m, 4H), 7.37-7.18 (m, 6H), 6.96 (d, J = 8Hz, 1H) = 9 Hz, 1H), 4.22 (d, J = 15 Hz, 1H), 4.15-3.94 (m, 1H), 3.94-3.70 s, 2H), 2.68 (t, J = 6 Hz, 2H), 2.63 - 2.35 (m, 8H).
[2779] Dihydrochloride:
[2780] TLC: Rf 0.28 (ethyl acetate: acetic acid: water = 3: 1: 1);
[2781] _{NMR (CD 3 OD): δ} 7.90-7.22 (m, 13H), 6.13-6.00 (m, 1H), 4.68-4.35 (m, 2H), 4.46 (s, 2H), 4.10-3.40 (m, 12H) .
[2782] Example 35 (44)
[2783] Diethylcarbamoylmethyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2784]
[2785] TLC: Rf 0.40 (ethyl acetate);
[2786] _{NMR (CDCl 3): δ 7.83-7.77} (m, 2H), 7.68-7.59 (m, 1H), 7.56-7.45 (m, 3H), 7.32 (d, J = 7.6Hz, 1H), 7.01 (d, J = 7.6 Hz, 1H), 5.44 (d, J = 8.8 Hz, 1H), 4.59 (d, J = 14.5 Hz, 1H) J = 7.0 Hz, 2H), 1.22 (t, J = 7.0 Hz, 2H), 3.74 (dd, J = 15.0, 8.8 Hz, 1H) 7.0 Hz, 3H), 1.14 (t, J = 7.0 Hz, 3H).
[2787] Example 35 (45)
[2788] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2789]
[2790] TLC: Rf 0.27 (hexane: AcOEt = 1: 2);
[2791] _{NMR (DMSO-d 6):} δ 7.82-7.72 (m, 4H), 7.68-7.60 (m, 2H), 7.50 (d, J = 8.0Hz, 1H), 7.41 (d, J = 8.0Hz, 1H) , 5.60 (dd, J = 9.0, 1.2 Hz, 1H), 5.04 (d, J = 16.0 Hz, 1H), 4.90 1H), 4.00 (dd, J = 15.2, 9.0 Hz, 1H).
[2792] Example 35 (46)
[2793] Methyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2794]
[2795] Free body:
[2796] TLC: Rf 0.27 (ethyl acetate);
[2797] _{NMR (CDCl 3): δ 8.37-8.36} (m, 1H), 8.31-8.29 (m, 1H), 7.76-7.71 (m, 3H), 7.66-7.61 (m, 1H), 7.49-7.43 (m, 3H J = 12.5 Hz, 1H), 4.15 (d, J = 12.5 Hz, 1H) (dd, J = 15.0, 1.0 Hz, 1H), 3.90 (s, 3H), 3.81 (dd, J = 15.0, 9.5 Hz, 1H).
[2798] Hydrochloride:
[2799] TLC: Rf 0.27 (ethyl acetate);
[2800] _{NMR (DMSO-d 6):} δ 8.76 (d, J = 2.5Hz, 1H), 8.52 (d, J = 5.0Hz, 1H), 8.15 (dd, J = 8.5, 2.5Hz, 1H), 7.93-7.74 (m, 5H), 7.65-7.60 (m, 3H), 5.78 (d, J = 8.5 Hz, 1H), 5.35 J = 15.0, 8.5 Hz, 1 H), 3.69 (s, 3 H).
[2801] Example 35 (47)
[2802] Nitro-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2803]
[2804] TLC: Rf 0.34 (hexane: AcOEt = 1: 2);
[2805] _{NMR (CDCl 3): δ 7.86-7.70} (m, 4H), 7.63-7.54 (m, 2H), 7.41 (d, J = 8.8Hz, 1H), 5.69 (dd, J = 9.0, 1.8Hz, 1H) J = 15.0, 1.8 Hz, 1H), 3.75 (dd, J = 15.0, 9.0 Hz, 1H), 3.68-3.52 (m, 2H) , &Lt; / RTI &gt; 2H), 1.46 (s, 9H).
[2806] Example 35 (48)
[2807] 5 - ((2E) -3-ethoxycarbonyl-2-propenyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2808]
[2809] TLC: Rf 0.41 (hexane: AcOEt = 1: 1);
[2810] _{NMR (CDCl 3): δ 7.72-7.65} (m, 3H), 7.62-7.46 (m, 4H), 7.15 (dd, J = 8.7, 2.1Hz, 1H), 7.08 (dt, J = 15.6, 4.2Hz, 2H), 4.24 (q, J = 7.2 Hz, 2H), 6.20 (dt, J = 15.6, 2.1 Hz, 1H), 5.01 (dd, J = 8.7, 4.8 Hz, ), 3.77 (dd, J = 14.7, 4.8 Hz, 1H), 3.70 (dd, J = 14.7, 8.7 Hz, 1H), 1.31 (t, J = 7.2 Hz, 3H).
[2811] Example 35 (49)
[2812] Dimethylamino-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2813]
[2814] Free body:
[2815] TLC: Rf 0.35 (ethyl acetate);
[2816] _{NMR (CDCl 3): δ 7.69} (dd, J = 6.9, 1.5Hz, 1H), 7.64-7.50 (m, 5H), 7.46-7.41 (m, 2H), 7.01 (d, J = 8.0Hz, 1H) , 6.45 (d, J = 2.5 Hz, 1H), 6.43 (dd, J = 8.0, 2.5 Hz, 1H), 6.06 (dd, J = 9.3, 1.2 Hz, 1H) 1H), 3.91 (d, J = 14.1 Hz, 1H), 3.85 (dd, J = 15.0, 1.2 Hz, 1H) Hz, 1H), 3.66 (d, J = 13.0 Hz, 1H), 3.65 (dd, J = 15.0, 9.3 Hz, 1H).
[2817] Hydrochloride:
[2818] TLC: Rf 0.35 (ethyl acetate);
[2819] _{NMR (DMSO-d 6):} δ 9.40 (br, 2H), 8.20-8.11 (m, 1H), 7.86-7.59 (m, 7H), 7.42 (d, J = 8.4Hz, 1H), 6.61-6.56 ( (m, 2H), 6.09 (dd, J = 6.8, 3.0 Hz, 1H), 4.65 (d, J = 13.8 Hz, 1H) ), 3.88-3.85 (m, 2H), 3.80 (s, 3H), 3.79 (s, 3H).
[2820] Example 35 (50)
[2821] 4-Pyridin-3-ylmethyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene dihydrochloride
[2822]
[2823] TLC: Rf 0.44 (CHCl 3: MeOH = 9: 1);
[2824] _{NMR (CD 3 OD): δ} 9.21 (s, 1H), 8.95 (d, J = 5.6Hz, 1H), 8.92-8.84 (m, 1H), 8.22 (dd, J = 6.6, 2.2Hz, 1H), (Dd, J = 8.0, 5.6 Hz, 1H), 7.93-7.74 (m, 5H), 7.68-7.58 (m, 2H), 6.20 J = 13.2 Hz, 1H), 4.83-4.70 (m, 3H), 3.92 (dd, J = 15.4, 8.6 Hz, 1H), 3.77 (dd, J = 15.4, 1.6 Hz, 1H).
[2825] Example 35 (51)
[2826] 4- (2-dimethylaminoethyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene dihydrochloride
[2827]
[2828] TLC: Rf 0.51 (chloroform: methanol: triethylamine = 9: 1: 1);
[2829] _{NMR (DMSO-d 6):} δ 10.85-10.50 (br, 1H), 10.10-9.75 (br, 1H), 9.72-9.40 (br, 1H), 8.22 (dd, J = 5.4, 3.0Hz, 1H), J = 1.5 Hz, 1H), 4.72 (brd, J = 12.0 Hz, 1H), 7.90-7.85 (m, 2H), 7.82-7.75 ), 4.51 (brd, J = 12.0 Hz, 1H), 3.91-3.84 (m, 2H), 3.70-3.30 (m, 4H), 2.85 (s, 6H).
[2830] Example 35 (52)
[2831] Methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene hydrochloride (4-
[2832]
[2833] TLC: Rf 0.53 (CHCl 3: MeOH = 9: 1);
[2834] _{NMR (DMSO-d 6):} δ 10.15-9.90 (br, 1H), 8.24 (d, J = 6.6Hz, 1H), 7.95-7.72 (m, 5H), 7.69-7.58 (m, 2H), 6.16 ( (brd, J = 13.8 Hz, 1H), 4.70 (brd, J = 13.8 Hz, 1H), 4.02 (dd, J = 15.0 , 8.7 Hz, 1H), 3.94-3.70 (m, 4H), 3.82 (d, J = 15.0 Hz, 1H), 3.47-3.18 (m, 3H), 3.12-2.92 (m, 1H).
[2835] Example 35 (53)
[2836] Methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene hydrochloride
[2837]
[2838] TLC: Rf 0.46 (methylene chloride: methanol = 9: 1);
[2839] _{NMR (DMSO-d 6):} δ 9.40-9.10 (br, 2H), 8.16 (dd, J = 6.3, 2.4Hz, 1H), 7.91-7.75 (m, 5H), 7.68-7.59 (m, 2H), (Dd, J = 7.5, 2.4 Hz, 1H), 4.90-4.30 (br, 1H), 4.75-4.63 (m, 1H), 4.50-4.35 2H), 3.58-3.47 (m, 4H), 3.28-3.15 (m, 2H), 3.74 (d, J = .
[2840] Example 35 (54)
[2841] 4-Benzylpiperazin-1-yl) methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2842]
[2843] Free body:
[2844] TLC: Rf 0.29 (CHCl 3: MeOH = 19: 1);
[2845] _{NMR (CDCl 3): δ 7.68-7.57} (m, 4H), 7.56-7.50 (m, 2H), 7.50-7.42 (m, 2H), 7.36-7.20 (m, 5H), 6.33 (d, J = 9.0 J = 15.0 Hz, 1H), 3.72 (dd, J = 15.0, 9.0 Hz, 1H), 3.51 (s, 2H) 3.41 (d, J = 14.1 Hz, 1H), 2.70-2.25 (m, 8H).
[2846] Dihydrochloride:
[2847] TLC: Rf 0.29 (CHCl 3: MeOH = 19: 1);
[2848] _{NMR (DMSO-d 6):} δ 8.30-7.95 (br, 1H), 7.93-7.72 (m, 5H), 7.70-7.55 (m, 4H), 7.50-7.40 (m, 3H), 6.65-6.20 (br J = 15.6, 9.0 Hz, 1H), 3.84 (d, J = 15.6 Hz, 1H), 3.70 (br, 2H) 2.80 (m, 6 H).
[2849] Example 35 (55)
[2850] Yl) methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2851]
[2852] Free body:
[2853] TLC: Rf 0.43 (CHCl 3: MeOH = 19: 1);
[2854] _{NMR (CDCl 3): δ 8.23-8.16} (m, 1H), 7.71-7.52 (m, 6H), 7.52-7.42 (m, 3H), 6.68-6.62 (m, 2H), 6.30 (d, J = 9.0 J = 15.0 Hz, 1H), 3.76 (dd, J = 15.0, 9.0 Hz, 1H), 3.62-3. (D, J = 14.1 Hz, 1H), 2.73-2.61 (m, 2H), 2.58-2.44 (m, 2H).
[2855] Trihydrochloride:
[2856] TLC: Rf 0.43 (CHCl 3: MeOH = 19: 1);
[2857] _{NMR (DMSO-d 6):} δ 12.05-11.70 (br, 1H), 8.35 (d, J = 6.3Hz, 1H), 8.15-8.09 (m, 1H), 7.96-7.84 (m, 3H), 7.83- J = 8.7 Hz, 1H), 6.93 (t, J = 6.3 Hz, 1H), 6.46 (d, J = 8.7 Hz, 1H), 7.75 (m, 3H), 7.68-7.58 ), 4.87 (d, J = 13.8 Hz, 1H), 4.62 (d, J = 13.8 Hz, 1H), 4.55-4.30 (d, J = 15.0 Hz, 1H), 3.72-3.50 (m, 2H), 3.50-3.15 (m, 4H).
[2858] Example 35 (56)
[2859] Methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2860]
[2861] Free body:
[2862] TLC: Rf 0.45 (CHCl 3: MeOH = 19: 1);
[2863] _{NMR (CDCl 3): δ 7.69-7.52} (m, 6H), 7.51-7.41 (m, 2H), 6.16 (d, J = 9.0Hz, 1H), 4.71 (d, J = 14.4Hz, 1H), 4.15 (d, J = 15.0, 9.0 Hz, 1H), 3.54-3.39 (m, 5H), 2.55-2.46 (q, J = 7.2 Hz, 2H), 3.91 m, 2H), 2.41-2.29 (m, 2H), 1.27 (t, J = 7.2 Hz, 3H).
[2864] Hydrochloride:
[2865] TLC: Rf 0.45 (CHCl 3: MeOH = 19: 1);
[2866] _{NMR (DMSO-d 6):} δ 11.60-11.30 (br, 1H), 8.40-8.20 (br, 1H), 8.00-7.74 (m, 5H), 7.68-7.58 (m, 2H), 6.31 (brd, J = 8.1 Hz, 1H), 4.98-4.70 (m, 1H), 4.70-4.52 (m, 1H), 4.20-3.89 (m, 2H), 4.07 J = 15.3 Hz, 1H), 3.77-3.60 (m, 1H), 3.52-2.90 (m, 6H), 1.18 (t, J = 7.2 Hz, 3H).
[2867] Example 35 (57)
[2868] Yl) methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2869]
[2870] Free body:
[2871] TLC: Rf 0.31 (CHCl 3: MeOH = 9: 1);
[2872] _{NMR (CDCl 3): δ 7.70-7.50} (m, 6H), 7.50-7.41 (m, 2H), 6.29 (d, J = 9.0Hz, 1H), 4.72 (d, J = 14.1Hz, 1H), 3.91 (d, J = 15.0 Hz, 1H), 3.73 (dd, J = 15.0, 9.0 Hz, 1H), 3.63 -2.30 (m, 10H).
[2873] Dihydrochloride:
[2874] TLC: Rf 0.31 (CHCl 3: MeOH = 9: 1);
[2875] _{NMR (DMSO-d 6):} δ 11.50-10.60 (br, 1H), 8.30-8.00 (br, 1H), 7.88-7.73 (m, 5H), 7.67-7.58 (m, 2H), 6.60-6.30 (br J = 15.0, 8.7 Hz, 1H), 3.86 (d, J = 15.0 Hz, 1H), 3.81 (br, 3.74 (m, 2H), 3.73 - 2.80 (m, 10H).
[2876] Example 35 (58)
[2877] Yl) methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2878]
[2879] Free body:
[2880] TLC: Rf 0.36 (CHCl 3: MeOH = 9: 1);
[2881] _{NMR (DMSO-d 6):} δ 8.14 (d, J = 6.6Hz, 2H), 7.88-7.81 (m, 1H), 7.81-7.74 (m, 3H), 7.74-7.68 (m, 2H), 7.67- J = 9.0 Hz, 1H), 4.16 (d, J = 14.4 Hz, 1H), 4.05 (dd, J = J = 15.0 Hz, 1H), 3.57 (d, J = 14.4 Hz, 1H), 3.42-3.18 (m, 4H), 2.43 (t, J = 4.8 Hz, 4H).
[2882] Trihydrochloride:
[2883] TLC: Rf 0.36 (CHCl 3: MeOH = 9: 1);
[2884] _{NMR (DMSO-d 6):} δ 14.20-13.80 (br, 1H), 12.30-11.90 (br, 1H), 8.46-8.20 (br, 1H), 8.35 (d, J = 6.9Hz, 2H), 7.98- J = 8.7 Hz, 1H), 5.05 (m, 2H), 7.82-7.74 (m, 3H), 7.67-7.57 1H), 3.75-3.55 (m, 6H), 3.84 (m, 2H) (d, J = 15.3 Hz, 1H).
[2885] Example 35 (59)
[2886] 4-Benzylaminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide To a solution of benzo [b] thiophene
[2887]
[2888] Free body
[2889] TLC: Rf 0.46 (ethyl acetate);
[2890] _{NMR (CDCl 3): δ 7.74} (dd, J = 7.2, 1.5Hz, 1H), 7.65-7.51 (m, 5H), 7.45-7.40 (m, 2H), 7.36-7.25 (m, 5H), 5.84 ( (d, J = 9.3,1.0 Hz, 1H), 4.49 (d, J = 14.1 Hz, 1H), 3.98 J = 15.0, 1.0 Hz, 1H), 3.77 (d, J = 12.7, 1H), 3.65 (dd, J = 15.0, 9.3 Hz, 1H).
[2891] Hydrochloride:
[2892] TLC: Rf 0.49 (ethyl acetate: triethylamine = 6: 0.5);
[2893] _{NMR (DMSO-d 6):} δ 9.87 (brs, 1H), 9.57 (brs, 1H), 8.16 (d, J = 6.6Hz, 1H), 7.90-7.75 (m, 3H), 7.75-7.57 (m, (D, J = 13.5 Hz, 1H), 4.40 (d, J = 13.5 Hz, 1H), 4.30 (s, 2H), 7.50-7.41 ), 3.93-3.80 (m, 2H).
[2894] Example 35 (60)
[2895] 4-yl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2896]
[2897] Free body:
[2898] TLC: Rf 0.30 (ethyl acetate: methanol = 2: 1);
[2899] NMR (CDCl ₃ ): 7.70 (dd, J = 7.3, 1.3 Hz, 1H), 7.65-7.41 (m, 7H), 7.32-7.24 J = 15.0, 1H), 3.72 (dd, J = 14.0 Hz, 1H), 4.61 2H), 2.90-2.81 (m, 2H), 2.58-2.51 (m, 1H), 2.09-1.96 (m, 3H), 1.83-1.79 1.38 (m, 2H).
[2900] Dihydrochloride:
[2901] TLC: Rf 0.30 (ethyl acetate: methanol = 2: 1);
[2902] _{NMR (CD 3 OD): δ} 8.16-8.12 (m, 1H), 7.91-7.74 (m, 5H), 7.65-7.49 (m, 7H), 6.06 (dd, J = 8.4, 1.8Hz, 1H), 4.84 J = 15.4, 1.8 Hz, 1 H), 3.80-3.60 (m, 3H), 3.48 (m, 2H) ), 3.30-3.15 (m, 2H), 2.58-2.43 (m, 2H), 2.35-2.13 (m, 2H).
[2903] Example 35 (61)
[2904] Synthesis of 4- (morpholin-4-yl) methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2905]
[2906] Free body:
[2907] TLC: Rf 0.34 (hexane: AcOEt = 1: 2);
[2908] _{NMR (CDCl 3): δ 7.68-7.51} (m, 6H), 7.48-7.42 (m, 2H), 6.21 (dd, J = 9.3, 0.9Hz, 1H), 4.68 (d, J = 14.3Hz, 1H) (Dd, J = 15.0, 0.9 Hz, 1H), 3.74 (dd, J = 15.0, 9.3 Hz, 1H), 3.74-3.64 (m, 4H), 3.45 2.58-2.52 (m, 2H), 2.40-2.33 (m, 2H).
[2909] Hydrochloride:
[2910] TLC: Rf 0.34 (hexane: AcOEt = 1: 2);
[2911] _{NMR (DMSO-d 6):} δ 11.48 (br, 1H), 8.31 (d, J = 7.2Hz, 1H), 7.94-7.79 (m, 5H),
[2912] 2H), 6.44 (d, J = 8.1 Hz, 1H), 4.85-4.79 (m, 1H), 4.62-4.57 (m, 1H), 4.05-3.81 3.13 (m, 4 H).
[2913] Example 35 (62)
[2914] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2915]
[2916] TLC: Rf 0.18 (methylene chloride);
[2917] _{NMR (CDCl 3): δ 8.24} (dd, J = 7.8Hz, 1.5Hz, 1H), 7.86 (dd, J = 7.8Hz, 1.5Hz, 1H), 7.75 (t, J = 7.8Hz, 1H), 7.71 2H), 3.94 (dd, J = 15.0 Hz, 1 H), 7.96 (m, 1.5 Hz, 1H), 3.77 (dd, J = 15.0 Hz, 9.3 Hz, 1H), 1.47 (t, J = 7.2 Hz, 3H).
[2918] Example 35 (63)
[2919] Benzyloxycarbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2920]
[2921] TLC: Rf 0.37 (chloroform: ethyl acetate = 19: 1);
[2922] _{NMR (CDCl 3): δ 8.26} (dd, J = 7.5, 1.2Hz, 1H), 7.85 (dd, J = 7.8, 1.2Hz, 1H), 7.78-7.70 (m, 1H), 7.69-7.60 (m, 3H), 7.55-7.47 (m, 4H), 7.47-7.35 (m, 3H), 6.13 (dd, J = 9.3, 1.2 Hz, 1H) J = 12.3 Hz, 1H), 3.91 (dd, J = 15.0, 1.2 Hz, 1H), 3.73 (dd, J = 15.0, 9.3 Hz, 1H).
[2923] Example 35 (64)
[2924] 4-Pyridin-3-yl) -3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene hydrochloride
[2925]
[2926] TLC: Rf 0.55 (CHCl 3: MeOH = 9: 1);
[2927] _{NMR (DMSO-d 6):} δ 9.11 (s, 1H), 8.86 (d, J = 5.4Hz, 1H), 8.57 (d, J = 5.4Hz, 1H), 7.99-7.84 (m, 4H), 7.73 J = 7.2, 3.0 Hz, 1H), 4.07 (dd, J = 15.3, 7.2 Hz, 1H), 7.56-7.43 (m, , 1H), 4.01 (dd, J = 15.3, 3.0 Hz, 1H).
[2928] Example 35 (65)
[2929] 6-Pyridin-3-yl) -3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene hydrochloride
[2930]
[2931] TLC: Rf 0.60 (CHCl 3: MeOH = 9: 1);
[2932] _{NMR (DMSO-d 6):} δ 9.29 (d, J = 2.1Hz, 1H), 8.85 (d, J = 5.1Hz, 1H), 8.76 (d, J = 7.8Hz, 1H), 8.37 (s, 1H ), 8.29 (dd, J = 8.4, 2.1 Hz, 1H), 7.96 (dd, J = 8.4, 5.1 Hz, 1H), 7.89-7.75 (m, 4H), 7.71-7.60 (m, 2H) (Dd, J = 9.3, 3.0 Hz, 1H), 4.06 (dd, J = 15.0, 9.3 Hz, 1H), 3.85 (dd, J = 15.0, 3.0 Hz, 1H).
[2933] Example 35 (66)
[2934] Dihydrooxazol-2-yl) -3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[2935]
[2936] TLC: Rf 0.22 (ethyl acetate: hexane = 1: 1);
[2937] _{NMR (CDCl 3): δ 8.23} (d, J = 6.0Hz, 1H), 7.73-7.67 (m, 2H), 7.67-7.54 (m, 3H), 7.48-7.40 (m, 2H), 6.36 (dd, J = 9.0 Hz, 1.8 Hz, 1H), 4.26 (d, J = 7.5 Hz, 1H), 4.22 3.78 (dd, J = 15.0 Hz, 9.0 Hz, 1H), 1.50 (s, 3H), 1.45 (s, 3H).
[2938] Example 35 (67)
[2939] 6-Bromo-3-phenylsulfonyl-2,3-dihydro-l, l-dioxide benzo [b] thiophene
[2940]
[2941] TLC: Rf 0.24 (methylene chloride);
[2942] _{NMR (DMSO-d 6):} δ 8.13 (d, J = 2.0Hz, 1H), 8.02 (dd, J = 8.5, 2.0Hz, 1H), 7.83-7.76 (m, 3H), 7.67-7.60 (m, 3H), 5.79 (dd, J = 9.5, 3.0 Hz, 1H), 4.05 (dd, J = 15.5, 9.5 Hz, 1H), 3.85 (dd, J = 15.5, 3.0 Hz, 1H).
[2943] Example 35 (68)
[2944] 6-amino-3-phenylsulfonyl-2,3-dihydro-1,1-dioxo [b] thiophene
[2945]
[2946] TLC: Rf 0.34 (hexane: AcOEt = 1: 2);
[2947] _{NMR (DMSO-d 6):} δ 7.79-7.71 (m, 3H), 7.64-7.56 (m, 2H), 7.28 (d, J = 8.5Hz, 1H), 6.89 (dd, J = 8.5, 2.2Hz, J = 9.2, 3.0 Hz, 1H), 3.89 (dd, J = 15.2, 9.2 Hz, 1H), 6.71 (d, J = 3.64 (dd, J = 15.2, 3.0 Hz, 1 H).
[2948] Examples 36 to 36 (3)
[2949] 4-carboxy-1,1-dioxide benzo [b] thiophene was treated in the same manner as in Example 28 using an amine derivative corresponding to the corresponding carboxylic acid and (pyridin-3-ylmethyl) amine The following compounds of the present invention were obtained.
[2950] Example 36
[2951] 5-methylcarbamoyl-4-methoxy-l, l-dioxo [b] thiophene
[2952]
[2953] TLC: Rf 0.38 (methanol: ethyl acetate = 5: 95);
[2954] _{NMR (DMSO-d 6):} δ 8.40 (d, J = 4.8Hz, 1H), 7.75 (d, J = 7.0Hz, 1H), 7.65 (d, J = 7.8Hz, 1H), 7.59 (d, J = 7.8 Hz, 1H), 7.44 (d, J = 7.0 Hz, 1H), 3.89 (s, 3H), 2.78 (d, J = 4.8 Hz, 3H).
[2955] Example 36 (1)
[2956] 4-dimethylcarbamoyl-l, l-dioxide &lt; / RTI &gt; benzo [b] thiophene
[2957]
[2958] TLC: Rf 0.34 (methanol: ethyl acetate = 5: 95);
[2959] _{NMR (CDCl 3): δ 7.76} (dd, J = 7.0Hz, 1.4Hz, 1H), 7.58 (t, J = 7.0Hz, 1H), 7.51 (dd, J = 7.0Hz, 1.4Hz, 1H), 7.33 (d, J = 6.8 Hz, IH), 6.78 (d, J = 6.8 Hz, IH), 3.17 (s, 3H), 3.00 (s, 3H).
[2960] Example 36 (2)
[2961] 4-Carbamoyl-l, l-dioxide &lt; / RTI &gt; benzo [b] thiophene
[2962]
[2963] TLC: Rf 0.50 (methanol: ethyl acetate = 5: 95);
[2964] _{NMR (DMSO-d 6):} δ 8.22 (brs, 1H), 7.96 (d, J = 7.2Hz, 1H), 7.88 (d, J = 8.0Hz, 1H), 7.78 (brs, 1H), 7.67 (t J = 8.0 Hz, 1H), 7.55 (d, J = 8.0 Hz, 1H), 7.43 (d, J = 7.2 Hz, 1H).
[2965] Example 36 (3)
[2966] 4- (furan-2-ylmethyl) carbamoyl-l, l-dioxide benzo [b] thiophene
[2967]
[2968] TLC: Rf 0.36 (ethyl acetate: hexane = 1: 1);
[2969] NMR (CDCl ₃ + DMSO-d ₆ ): 7.96 (dd, J = 7.2, 0.9 Hz, 1H), 7.81-7.76 (m, 2H), 7.56 (t, J = 7.8 Hz, 1H), 7.51 J = 5.7 Hz, 1H), 7.40-7.38 (m, 1H), 6.78 (d, J = 7.2 Hz, 1H), 6.37-6.30 .
[2970] Examples 37 to 37 (6)
[2971] The operation was carried out in the same manner as in Example 18 using the corresponding alcohol derivative and the corresponding halide corresponding to 4-nitrobenzyl bromide in the compound prepared in Example 9 (12), or by using 4-hydroxy-1,1 -Dioxane benzo [b] thiophene and the corresponding alcohol derivative of 1- (3-hydroxypropyl) pyrrole in the same manner as in the method of Example 29, the following compounds of the present invention were obtained .
[2972] Example 37
[2973] 4- (2- (pyridin-4-yl) ethyl) oxy-1,1-dioxide benzo [b] thiophene
[2974]
[2975] TLC: Rf 0.23 (hexane: AcOEt = 1: 3);
[2976] _{NMR (CDCl 3): δ 8.56} (d, J = 6.0Hz, 2H), 7.46 (t, J = 8.0Hz, 1H), 7.31 (d, J = 7.2Hz, 1H), 7.29 (d, J = 8.0 J = 8.0 Hz, 1H), 6.60 (d, J = 7.2 Hz, 1H), 4.33 (t, J = 6.5 Hz, 1H) 2H), 3.14 (t, J = 6.5 Hz, 2H).
[2977] Example 37 (1)
[2978] 4- (2- (pyridin-3-yl) ethyl) oxy-1, 1-dioxide benzo [b] thiophene
[2979]
[2980] TLC: Rf 0.38 (ethyl acetate);
[2981] _{NMR (CDCl 3): δ 8.56} (d, J = 1.8Hz, 1H), 8.52 (dd, J = 4.8, 1.8Hz, 1H), 7.60 (d, J = 8.2Hz, 1H), 7.45 (t, J J = 7.6 Hz, 1H), 7.35 (d, J = 7.6 Hz, 1H), 7.28 J = 6.4 Hz, 2H), 6.60 (d, J = 7.0 Hz, 1H), 4.30 (t, J = 6.4 Hz, 2H).
[2982] Example 37 (2)
[2983] 4-ethoxycarbonylmethyloxy-1,1-dioxide benzo [b] thiophene
[2984]
[2985] TLC: Rf 0.38 (hexane: AcOEt = 1: 1);
[2986] _{NMR (CDCl 3): δ 7.53} (d, J = 7.2Hz, 1H), 7.47 (t, J = 8.0Hz, 1H), 7.34 (d, J = 8.0Hz, 1H), 6.94 (d, J = 8.0 J = 7.0 Hz, 3H), 6.65 (d, J = 7.2 Hz, 1H), 4.72 (s, 2H), 4.27 (q, J = 7.0 Hz, 2H).
[2987] Example 37 (3)
[2988] 6-ethoxycarbonylmethyloxy-1,1-dioxide benzo [b] thiophene
[2989]
[2990] TLC: Rf 0.30 (hexane: AcOEt = 1: 1);
[2991] _{NMR (CDCl 3): δ 7.28} (d, J = 8.4Hz, 1H), 7.24 (d, J = 2.6Hz, 1H), 7.17 (d, J = 7.0Hz, 1H), 7.05 (dd, J = 8.4 , 2.6 Hz, 1H), 6.63 (d, J = 7.0 Hz, 1H), 4.68 (s, 2H), 4.29 (q, J = 7.0 Hz, 2H), 1.31 (t,
[2992] Example 37 (4)
[2993] 6-Cyanomethyloxy-1,1-dioxo [b] thiophene
[2994]
[2995] TLC: Rf 0.30 (hexane: AcOEt = 1: 1);
[2996] _{NMR (CDCl 3): δ 7.36} (d, J = 8.4Hz, 1H), 7.34 (dd, J = 2.6, 0.8Hz, 1H), 7.20 (dd, J = 7.0, 0.8Hz, 1H), 7.14 (dd , J = 8.4, 2.6 Hz, 1H), 6.69 (d, J = 7.0 Hz, 1H), 4.84 (s, 2H).
[2997] Example 37 (5)
[2998] 5-ethoxycarbonylmethyloxy-1,1-dioxide benzo [b] thiophene
[2999]
[3000] TLC: Rf 0.31 (ethyl acetate: hexane = 1: 1);
[3001] _{NMR (CDCl 3): δ 7.64} (d, J = 8.2Hz, 1H), 7.15 (d, J = 6.8Hz, 1H), 6.98-6.86 (m, 2H), 6.74 (d, J = 6.8Hz, 1H ), 4.69 (s, 2H), 4.29 (q, J = 7.2 Hz, 2H), 1.31 (t, J = 7.2 Hz, 3H).
[3002] Example 37 (6)
[3003] 7-Ethoxycarbonylmethyloxy-1,1-dioxide benzo [b] thiophene
[3004]
[3005] TLC: Rf 0.28 (ethyl acetate: hexane = 1: 1);
[3006] _{NMR (CDCl 3): δ 7.46} (dd, J = 8.6Hz, 7.0Hz, 1H), 7.14 (d, J = 7.0Hz, 1H), 6.96 (d, J = 7.0Hz, 1H), 6.89 (d, J = 8.6 Hz, 1H), 6.68 (d, J = 7.0 Hz, 1H), 4.84 (s, 2H), 4.28 .
[3007] Examples 38 to 38 (3)
[3008] 4-carboxy-1,1-dioxide benzo [b] thiophene The title compound was obtained in the same manner as in Example 32 using the corresponding carboxylic acid derivative and bromoethane as the corresponding halide, Compound.
[3009] Example 38
[3010] 5-Benzyloxycarbonyl-4-methoxy-1,1-dioxo [b] thiophene
[3011]
[3012] TLC: Rf 0.28 (hexane: AcOEt = 2: 1);
[3013] _{NMR (CDCl 3): δ 7.98} (d, J = 8.0Hz, 1H), 7.51-7.36 (m, 7H), 6.73 (d, J = 7.0Hz, 1H), 5.38 (s, 2H), 3.87 (s , 3H).
[3014] Example 38 (1)
[3015] 5-ethoxycarbonyl-1,1-dioxide benzo [b] thiophene
[3016]
[3017] TLC: Rf 0.43 (hexane: AcOEt = 1: 1);
[3018] _{NMR (CDCl 3): δ 8.22} (dd, J = 8.0, 1.0Hz, 1H), 8.03 (d, J = 1.0Hz, 1H), 7.79 (d, J = 8.0Hz, 1H), 7.15 (d, J = 7.0 Hz, 1H), 6.80 (d, J = 7.0 Hz, 1H), 4.43 (q, J = 7.0 Hz, 1H), 1.42 (t, J = 7.0 Hz, 3H).
[3019] Example 38 (2)
[3020] 7-methoxycarbonyl-l, l-dioxide &lt; / RTI &gt; benzo [b] thiophene
[3021]
[3022] TLC: Rf 0.15 (hexane: AcOEt = 2: 1);
[3023] _{NMR (CDCl 3): δ 8.11} (d, J = 8Hz, 1H), 7.66 (t, J = 8Hz, 1H), 7.55 (d, J = 8Hz, 1H), 7.20 (d, J = 7Hz, 1H) , 6.77 (d, J = 7 Hz, 1 H), 4.05 (s, 3H).
[3024] Example 38 (3)
[3025] 7-ethoxycarbonyl-l, l-dioxo [b] thiophene
[3026]
[3027] TLC: Rf 0.39 (ethyl acetate: hexane = 1: 1);
[3028] _{NMR (CDCl 3): δ 8.13} (dd, J = 7.6Hz, 1.2Hz, 1H), 7.65 (t, J = 7.6Hz, 1H), 7.52 (dd, J = 7.6Hz, 1.2Hz, 1H), 7.18 (d, J = 6.8 Hz, 1H), 6.76 (d, J = 6.8 Hz, 1H), 4.53 (q, J = 7.2 Hz, 2H), 1.48 (t, J = 7.2 Hz, 1H).
[3029] Example 39
[3030] 5-t-Butoxycarbonyl-4-methoxy-l, l-dioxide &lt;
[3031]
[3032] A suspension of benzene (15 ml) of 5-carboxy-4-methoxy-1,1-dioxide benzo [b] thiophene (934 mg) was heated under reflux and dimethylformamide di-t-butyl acetal (4.02 g) And the mixture was heated to reflux for 1 hour. Water was added to the reaction mixture and extracted with benzene. The extract was washed successively with saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous sodium sulfate and concentrated. The residue was purified by silica gel column chromatography (ethyl acetate: hexane = 1: 10) to obtain the compound (942 mg) of the present invention having the following physical data.
[3033] TLC: Rf 0.25 (ethyl acetate: hexane = 1: 4);
[3034] _{NMR (CDCl 3): δ 7.87} (d, J = 7.8Hz, 1H), 7.47 (d, J = 7.8Hz, 1H), 7.45 (d, J = 7.0Hz, 1H), 6.73 (d, J = 7.0 Hz, &lt; / RTI &gt; 1H), 3.95 (s, 3H), 1.62 (s, 9H).
[3035] Example 40
[3036] 5 - ((E) -2- (ethoxycarbonyl) ethenyl) -4-methoxybenzo [b] thiophene
[3037]
[3038] 62.5% Sodium hydride (920 mg) was suspended in anhydrous tetrahydrofuran (40 ml), and a solution of triethylphosphonoacetate (5.83 g) in anhydrous tetrahydrofuran (20 ml) was added dropwise at room temperature and stirred for 15 minutes. To the reaction mixture, anhydrous tetrahydrofuran (20 ml) solution of 5-formyl-4-methoxybenzo [b] thiophene (3.84 g) was added dropwise and the mixture was stirred at room temperature for 1 hour. Acetic acid (1.5 mL) was added to the reaction mixture and concentrated. The residue was purified by silica gel column chromatography (hexane: ethyl acetate = 9: 1) to obtain the present compound (5.17 g) having the following physical data.
[3039] TLC: Rf 0.37 (hexane: AcOEt = 5: 1);
[3040] _{NMR (CDCl 3): δ 8.13} (d, J = 16.2Hz, 1H), 7.62-7.41 (m, 4H), 6.53 (d, J = 16.2Hz, 1H), 4.29 (q, J = 7.2Hz, 2H ), 4.00 (s, 3H), 1.36 (t, J = 7.2 Hz, 3H).
[3041] Example 41
[3042] 5- (2- (ethoxycarbonyl) ethyl) -4-methoxybenzo [b] thiophene
[3043]
[3044] The compound (5.16 g) prepared in Example 40 was dissolved in ethanol (100 ml), 10% palladium carbon (200 mg) was added, and the mixture was stirred at room temperature under a hydrogen atmosphere. The reaction mixture was filtered through celite and the filtrate was concentrated. The residue was purified by silica gel column chromatography (hexane: ethyl acetate = 9: 1) to obtain the present compound (3.23 g) having the following physical data.
[3045] TLC: Rf 0.40 (hexane: AcOEt = 5: 1);
[3046] _{NMR (CDCl 3): δ 7.56} (d, J = 8.1Hz, 1H), 7.41 (q, J = 5.4Hz, 2H), 7.20 (d, J = 8.1Hz, 1H), 4.14 (q, J = 7.2 J = 8.0 Hz, 2H), 3.97 (s, 3H), 3.07 (t, J = 8.0 Hz, 2H), 2.66 (t,
[3047] Example 42
[3048] 5- (2- (ethoxycarbonyl) ethyl) -4-methoxy-1,1-dioxide benzo [b] thiophene
[3049]
[3050] The compound prepared in Example 41 was used instead of the compound prepared in Example 1, and the compound of the present invention having the following physical properties was obtained in the same manner as in Example 3 except that 3- Chloro and benzoic acid were used).
[3051] TLC: Rf 0.25 (hexane: AcOEt = 2: 1);
[3052] _{NMR (CDCl 3): δ 7.45-7.36} (m, 3H), 6.70 (d, J = 6.8Hz, 1H), 4.15 (q, J = 7.4Hz, 2H), 3.92 (s, 3H), 3.01 (t J = 7.6 Hz, 2H), 2.62 (t, J = 7.6 Hz, 2H), 1.24 (t, J = 7.4 Hz, 3H).
[3053] Example 43
[3054] 5 - (4,4-dimethyl-4,5-dihydrooxazol-2-yl) -1,1-dioxo [
[3055]
[3056] B) thiophene and (2-hydroxy-benzothiazol-3-ylmethyl) amine instead of 5-carboxy- 1,1-dimethylethyl) amine, the procedure of Example 28 was followed, and the obtained compound was treated in the same manner as in Example 34 to give the compound of the present invention having the following physical data .
[3057] TLC: Rf 0.39 (ethyl acetate: hexane = 1: 1);
[3058] _{NMR (CDCl 3): δ 8.08} (dd, J = 8.0Hz, 1.2Hz, 1H), 7.98 (d, J = 1.2Hz, 1H), 7.75 (d, J = 8.0Hz, 1H), 7.23 (d, J = 7.0 Hz, 1H), 6.77 (d, J = 7.0 Hz, 1H), 4.16 (s, 2H), 1.40 (s, 6H).
[3059] Examples 44 to 44 (24)
[3060] (2), Examples 37 to 37 (6), Examples 38 to 38 (3), Example 39, Example 42, Example 36 (3), the compound prepared in Example 43 or a derivative thereof and a thiol derivative corresponding to thiophenol were used in the same manner as in Example 1 to obtain the following compounds of the present invention.
[3061] Example 44
[3062] Methylcarbamoyl-4-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3063]
[3064] TLC: Rf 0.58 (methanol: ethyl acetate = 5: 95);
[3065] _{NMR (CDCl 3): δ 8.10} (d, J = 5.6Hz, 1H), 7.56 (d, J = 5.6Hz, 1H), 7.54-7.48 (m, 2H), 7.43-7.35 (m, 3H), 7.17 (s, 3H), 3.72 (dd, J = 9.4 Hz, 4.6 Hz, 1H), 3.63 (dd, J = 9.4 Hz, 1.4 Hz, 1H), 3.07 (d, J = 4.8 Hz, 3H).
[3066] Example 44 (1)
[3067] 4-dimethylcarbamoyl-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3068]
[3069] TLC: Rf 0.52 (methanol: ethyl acetate = 5: 95);
[3070] NMR (CDCl ₃ ): 7.78 (dd, J = 7.5 Hz, 1.8 Hz, 1H), 7.63-7.51 (m, 4H), 7.43-7.34 (Dd, J = 14.1 Hz, 7.8 Hz, 1H), 3.61 (dd, J = 14.1 Hz, 1.8 Hz, 1H), 3.17 (s, 3H), 3.00 (s, 3H).
[3071] Example 44 (2)
[3072] 4-Carbamoyl-3-phenylthio-2,3-dihydro-1,1-dioxo [
[3073]
[3074] TLC: Rf 0.49 (methanol: ethyl acetate = 5: 95);
[3075] _{NMR (DMSO-d 6):} δ 8.19 (brs, 1H), 7.96-7.64 (m, 4H), 7.52-7.30 (m, 5H), 5.87 (d, J = 7.4Hz, 1H), 4.10 (dd, J = 14.6 Hz, 7.4 Hz, 1H), 3.61 (d, J = 14.6 Hz, 1H).
[3076] Example 44 (3)
[3077] 3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3078]
[3079] TLC: Rf 0.44 (ethyl acetate: methanol = 10: 1);
[3080] _{NMR (CDCl 3): δ 8.50} (d, J = 6Hz, 2H), 7.60-7.13 (m, 9H), 7.07 (d, J = 8Hz, 1H), 4.93 (dd, J = 2, 7Hz, 1H) , 4.50-4.15 (m, 2H), 3.80-3.50 (m, 2H), 3.15 (t, J = 7 Hz, 2H).
[3081] Example 44 (4)
[3082] 3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3083]
[3084] TLC: Rf 0.38 (ethyl acetate);
[3085] _{NMR (CDCl 3): δ 8.57} (d, J = 1.8Hz, 1H), 8.48 (dd, J = 5.0Hz, 1.8Hz, 1H), 7.63 (m, 1H), 7.54-7.32 (m, 7H), (Dd, J = 7.8 Hz, 4.0 Hz, 1H), 7.05 (d, J = 8.0 Hz, 1H), 4.97 (dd, J = 14.2 Hz, 6.2 Hz, 1H), 3.58 (dd, J = 14.2 Hz, 1.8 Hz, 1H), 3.16 (t, J = 7.2 Hz, 2H).
[3086] Example 44 (5)
[3087] 3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3088]
[3089] TLC: Rf 0.45 (hexane: AcOEt = 1: 1);
[3090] _{NMR (CDCl 3): δ 7.57-7.53} (m, 2H), 7.49 (d, J = 8.1Hz, 1H), 7.38-7.33 (m, 4H), 6.96 (d, J = 8.1Hz, 1H), 5.16 J = 7.0, 1.8 Hz, 1H), 4.71 (s, 2H), 4.28 (q, J = 7.2 Hz, 2H), 3.72 (dd, J = J = 14.0, 1.8 Hz, 1H), 1.30 (t, J = 7.2 Hz, 3H).
[3091] Example 44 (6)
[3092] 6-ethoxycarbonylmethyloxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3093]
[3094] TLC: Rf 0.54 (hexane: AcOEt = 1: 1);
[3095] NMR (CDCl ₃ ): 7.62 (d, J = 8.7 Hz, 1H), 7.43-7.40 (m, 2H), 7.35-7.33 J = 7.2 Hz, 2H), 3.81 (dd, J = 6.8 Hz, 1H), 7.10 (d, J = 2.4 Hz, 13.7, 6.8 Hz, 1H), 3.52 (dd, J = 13.7, 6.8 Hz, 1H), 1.31 (t, J = 7.2 Hz, 3H).
[3096] Example 44 (7)
[3097] 6-Cyanomethyloxy-3-phenylthio-2,3-dihydro-1, 1-dioxide benzo [b] thiophene
[3098]
[3099] TLC: Rf 0.54 (hexane: AcOEt = 2: 1);
[3100] NMR (CDCl ₃ ): 隆 7.69 (d, J = 8.4 Hz, 1H), 7.44-7.41 (m, 2H), 7.38-7.34 , 7.24 (d, J = 2.4 Hz, 1H), 4.93 (t, J = 6.9 Hz, 1H), 4.83 (s, 2H), 3.83 (dd, J = 13.7, 6.9 Hz, 1H) J = 13.7, 6.9 Hz, 1 H).
[3101] Example 44 (8)
[3102] 5-ethoxycarbonylmethyloxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3103]
[3104] TLC: Rf 0.45 (ethyl acetate: hexane = 1: 1);
[3105] _{NMR (CDCl 3): δ 7.64} (d, J = 8.6Hz, 1H), 7.48-7.30 (m, 5H), 7.15 (d, J = 2.2Hz, 1H), 7.06 (dd, J = 8.6Hz, 2.2 J = 7.4 Hz, 2H), 3.79 (dd, J = 13.6 Hz, 7. 0 Hz, 1H) ), 3.50 (dd, J = 13.6 Hz, 7.0 Hz, 1H), 1.32 (t, J = 7.4 Hz, 3H).
[3106] Example 44 (9)
[3107] 3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3108]
[3109] TLC: Rf 0.43 (ethyl acetate: hexane = 1: 1);
[3110] NMR (CDCl ₃ ): 隆 7.55 (t, J = 8.4 Hz, 1H), 7.46-7.27 (m, 6H), 6.82 (d, J = 8.4 Hz, 1H) J = 7.6 Hz, 1H), 3.54 (dd, J = 13.6 Hz, 6.6 Hz, 1H), 4.80 (s, 2H), 4.26 , 1 H), 1.28 (t, J = 7.2 Hz, 3 H).
[3111] Example 44 (10)
[3112] Benzyloxycarbonyl-4-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3113]
[3114] TLC: Rf 0.55 (hexane: AcOEt = 1: 1);
[3115] _{NMR (CDCl 3): δ 7.99} (d, J = 8.0Hz, 1H), 7.54-7.34 (m, 1H), 5.40 (s, 2H), 5.08 (dd, J = 6.0, 2.5Hz, 1H), 3.97 (s, 3H), 3.69 (dd, J = 14.0, 6.0 Hz, 1H), 3.60 (dd, J = 14.0, 2.5 Hz, 1H).
[3116] Example 44 (11)
[3117] 5-ethoxycarbonyl-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3118]
[3119] TLC: Rf 0.55 (hexane: AcOEt = 1: 1);
[3120] _{NMR (CDCl 3): δ 8.36} (s, 1H), 8.20 (d, J = 8.2Hz, 1H), 7.78 (d, J = 8.2Hz, 1H), 7.47-7.33 (m, 5H), 4.97 (t J = 7.0 Hz, 1H), 4.44 (q, J = 7.0 Hz, 2H), 3.84 (dd, J = (t, J = 7.0 Hz, 3H).
[3121] Example 44 (12)
[3122] Methoxycarbonyl-3-phenylthio-2,3-dihydro-1, 1-dioxide benzo [b] thiophene
[3123]
[3124] TLC: Rf 0.39 (ethyl acetate: hexane = 1: 1);
[3125] _{NMR (CDCl 3): δ 8.12} (d, J = 7.8Hz, 1H), 7.93 (d, J = 7.8Hz, 1H), 7.72 (t, J = 7.8Hz, 1H), 7.48-7.33 (m, 5H (Dd, J = 7.6 Hz, 6.8 Hz, 1H), 4.01 (s, 3H), 3.86 (dd, J = 13.6 Hz, 7.6 Hz, 1H), 3.56 Hz, 1H).
[3126] Example 44 (13)
[3127] 3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3128]
[3129] TLC: Rf 0.60 (ethyl acetate: hexane = 1: 1);
[3130] _{NMR (CDCl 3): δ 8.13} (d, J = 7.8Hz, 1H), 7.91 (d, J = 7.8Hz, 1H), 7.72 (t, J = 7.8Hz, 1H), 7.46-7.38 (m, 2H J = 7.2 Hz, 2H), 3.84 (dd, J = 13.5 Hz, 7.8 Hz, 1H), 7.38-7.30 (m, 3H), 4.92 (dd, J = 7.8 Hz, 6.9 Hz, 1H), 3.55 (dd, J = 13.5 Hz, 6.9 Hz, 1H), 1.44 (t, J = 7.2 Hz, 3H).
[3131] Example 44 (14)
[3132] 5-t-Butoxycarbonyl-4-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3133]
[3134] TLC: Rf 0.22 (ethyl acetate: hexane = 1: 4);
[3135] _{NMR (CDCl 3): δ 7.88} (d, J = 8.0Hz, 1H), 7.58-7.49 (m, 2H), 7.46 (d, J = 8.0Hz, 1H), 7.43-7.34 (m, 3H), 5.10 (dd, J = 6.0 Hz, 2.8 Hz, 1H), 4.08 (s, 3H), 3.70 (dd, J = 13.8 Hz, 6.0 Hz, 1H) , &Lt; / RTI &gt; 1.63 (s, 9H).
[3136] Example 44 (15)
[3137] Methoxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3138]
[3139] TLC: Rf 0.25 (hexane: AcOEt = 2: 1);
[3140] _{NMR (CDCl 3): δ 7.55-7.50} (m, 2H), 7.44 (s, 2H), 7.43-7.30 (m, 3H), 5.08 (dd, J = 6.9, 2.1Hz, 1H), 4.15 (q, J = 7.2 Hz, 2H), 4.05 (s, 3H), 3.68 (dd, J = 15.2, 7.2 Hz, 1H), 3.60 (dd, J = 15.2, 2.1 Hz, 1H), 3.18-3.00 ), 2.66 (t, J = 7.8 Hz, 2H), 1.25 (t, J = 7.2 Hz, 3H).
[3141] Example 44 (16)
[3142] Yl) methyl] carbamoyl-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3143]
[3144] TLC: Rf 0.37 (ethyl acetate: benzene = 1: 2);
[3145] _{NMR (DMSO-d 6):} δ 9.24 (t, J = 5.6Hz, 1H), 7.93-7.82 (m, 2H), 7.77-7.66 (m, 1H), 7.55-7.51 (m, 1H), 7.47- J = 7.6 Hz, 1H), 4.46 (d, J = 5.6 Hz, 2H), 4.12 (dd, J = 14.2 Hz, 7.6 (m, 2H) Hz, 1 H), 3.62 (d, J = 14.2 Hz, 1 H).
[3146] Example 44 (17)
[3147] Dihydrooxazol-2-yl) -3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3148]
[3149] TLC: Rf 0.50 (ethyl acetate: hexane = 1: 1);
[3150] _{NMR (CDCl 3): δ 8.32} (brs, 1H), 8.12 (d, J = 8.2Hz, 1H), 7.75 (d, J = 8.2Hz, 1H), 7.50-7.30 (m, 5H), 4.96 (dd J = 7.2 Hz, 6.6 Hz, 1H), 4.18 (s, 2H), 3.82 (dd, J = 13.8 Hz, 7.2 Hz, 1H), 3.54 (dd, J = 13.8 Hz, 6.6 Hz, 1H) 1.42 (s, 6 H).
[3151] Example 44 (18)
[3152] 3-Benzylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3153]
[3154] TLC: Rf 0.52 (hexane: AcOEt = 1: 1);
[3155] _{NMR (CDCl 3): δ 3.42} (dd, J = 13.8Hz, 6.3Hz, 1H), 3.69 (dd, J = 13.8Hz, 7.8Hz, 1H), 3.78 (d, J = 13.7Hz, 1H), 3.86 (m, 2H), 7.59-7.62 (m, 2H), 7.27-7.33 ), 7.71 (d, J = 7.6 Hz, 1 H).
[3156] Example 44 (19)
[3157] Preparation of 3- (3,4-dichlorophenyl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3158]
[3159] TLC: Rf 0.57 (hexane: AcOEt = 1: 1);
[3160] _{NMR (CDCl 3): δ 3.48} (dd, J = 13.6Hz, 5.8Hz, 1H), 3.83 (dd, J = 13.6Hz, 7.6Hz, 1H), 4.97 (t- type, J = 6.8Hz, 1H) , 7.23 (dd, J = 8.3 Hz, 2.2 Hz, 1H), 7.41 (d, J = 8.3 Hz, 1H), 7.51 (d, J = 2.2 Hz, 1H), 7.54-7.62 -7.69 (m, 2H), 7.74 (d, J = 76 Hz, 1 H).
[3161] Example 44 (20)
[3162] Preparation of 3- (4-nitrophenyl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3163]
[3164] TLC: Rf 0.15 (methylene chloride);
[3165] NMR (CDCl ₃ ): 隆 3.55 (dd, J = 13.8 Hz, 6.0 Hz, 1H), 3.97 (dd, J = 13.8 Hz, 7.5 Hz, 1H) , 7.47 (d, J = 8.7 Hz, 2H), 7.55-7.64 (m, 1H), 7.68-7.70 Hz, 2H).
[3166] Example 44 (21)
[3167] 5-hydroxymethyl-4-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3168]
[3169] TLC: Rf 0.64 (ethyl acetate);
[3170] _{NMR (CDCl 3): δ 7.68} (d, J = 7.8Hz, 1H), 7.55-7.47 (m, 3H), 7.39-7.35 (m, 3H), 5.08 (dd, J = 6.6, 2.5Hz, 1H) , 4.84 (d, J = 6.0 Hz, 2H), 4.06 (s, 3H), 3.69 (dd, J = 13.9, 6.6 Hz, 1H), 3.58 (dd, J = 13.9, 2.5 Hz, 1H) t, J = 6.0 Hz, 1H).
[3171] Example 44 (22)
[3172] 3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3173]
[3174] TLC: Rf 0.22 (chloroform: ethyl acetate = 4: 1);
[3175] _{NMR (CDCl 3): δ 7.77-7.66} (m, 2H), 7.61 (d, J = 7.4Hz, 1H), 7.57-7.44 (m, 2H), 7.43-7.32 (m, 3H), 5.20 (dd, J = 6.8, 2.0 Hz, 1H), 5.03 (s, 2H), 3.72 (dd, J = 14.0, 6.8 Hz, 1H), 3.62 (dd, J = 14.0, 2.0 Hz, 1H), 2.45-2.15 , 1H).
[3176] Example 44 (23)
[3177] 6-Fluoro-3-phenylthio-2,3-dihydro-1,1-dioxide [0154] Benzo [b] thiophene
[3178]
[3179] TLC: Rf 0.62 (ethyl acetate: hexane = 1: 4);
[3180] NMR (CDCl ₃ ): 隆 7.70 (ddd, J = 7.6 Hz, 4.4 Hz, 0.4 Hz, 1H), 7.47-7.29 (m, 7H), 4.93 (t, J = 7.0 Hz, 1H) J = 13.8 Hz, 7.0 Hz, 1H), 3.55 (dd, J = 13.8 Hz, 7.0 Hz, 1H).
[3181] Example 44 (24)
[3182] Fluoro-3-phenylthio-2,3-dihydro-1, 1-dioxide benzo [b] thiophene
[3183]
[3184] TLC: Rf 0.55 (ethyl acetate: hexane = 1: 4);
[3185] _{NMR (CDCl 3): δ 7.64-7.45} (m, 4H), 7.42-7.27 (m, 4H), 5.06 (dd, J = 7.4Hz, 2.8Hz, 1H), 3.77 (dd, J = 14.2Hz, 7.4 Hz, 1H), 3.63 (dd, J = 14.2 Hz, 2.8 Hz, 1H).
[3186] Example 44 (45) to 45 (22)
[3187] The procedure of Example 3 was repeated using the compounds prepared in Examples 44 to 44 (15) and Examples 44 (18) to 44 (24) instead of the compound prepared in Example 1, Chloro-benzoic acid instead of oxone, and, if necessary, conversion into the corresponding salt by a known method to give the compound of the present invention shown below.
[3188] Example 45
[3189] 5-Methylcarbamoyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3190]
[3191] TLC: Rf 0.33 (methanol: ethyl acetate = 5: 95);
[3192] _{NMR (DMSO-d 6):} δ 8.47 (q- type, J = 3.4Hz, 1H), 7.87-7.73 (m, 3H), 7.69-7.60 (m, 3H), 7.50 (d, J = 5.4Hz, (D, J = 10.2 Hz, 6.0 Hz, 1H), 3.59 (s, 3H), 2.77 (d, (d, J = 3.4 Hz, 3H).
[3193] Example 45 (1)
[3194] 4-dimethylcarbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxo [b] thiophene
[3195]
[3196] TLC: Rf 0.55 (methanol: ethyl acetate = 5: 95);
[3197] NMR (DMSO-d ₆ ): 7.93-7.73 (m, 6H), 7.70-7.62 (m, 2H), 5.86 (d, J = 9.3 Hz, 1H), 4.12 , 3.91 (d, J = 15.3 Hz, 1H), 3.07 (s, 3H), 3.03 (s, 3H).
[3198] Example 45 (2)
[3199] 4-Carbamoyl-3-phenylsulfonyl-2,3-dihydro-1, 1-dioxo [
[3200]
[3201] TLC: Rf 0.43 (methanol: ethyl acetate = 5: 95);
[3202] _{NMR (DMSO-d 6):} δ 8.30 (brs, 1H), 8.03 (d, J = 7.8Hz, 1H), 7.91 (d, J = 7.8Hz, 1H), 7.86-7.72 (m, 5H), 7.68 (t, J = 7.8 Hz, 1H), 6.37 (d, J = 9.3 Hz, 1H), 4.08 (dd, J = 15.3 Hz, 9.3 Hz, 1H), 3.95 = 15.3 Hz, 1H).
[3203] Example 45 (3)
[3204] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3205]
[3206] Free body:
[3207] TLC: Rf 0.25 (ethyl acetate: methanol = 10: 1);
[3208] _{NMR (CDCl 3): δ 8.58} (d, J = 6Hz, 2H), 7.80-7.35 (m, 6H), 7.35-7.14 (m, 3H), 6.98 (d, J = 8Hz, 1H), 5.12 (d J = 9 Hz, 1H), 4.30-4.05 (m, 3H), 3.70 (dd, J = 9,15 Hz, 1H), 3.25-2.90 (m, 2H).
[3209] Hydrochloride:
[3210] TLC: Rf 0.25 (ethyl acetate: methanol = 10: 1);
[3211] _{NMR (DMSO-d 6):} δ 8.83 (d, J = 6.6Hz, 2H), 7.96 (d, J = 6.6Hz, 2H), 7.78-7.58 (m, 6H), 7.35-7.30 (m, 2H) , 5.40 (d, J = 8.5 Hz, IH), 4.36-4.28 (m, IH), 4.19-4.12 (m, IH), 4.11 , 8.5 Hz, 1 H), 3.24-3.15 (m, 1 H), 3.11-3.01 (m, 1 H).
[3212] Methanesulfonate:
[3213] TLC: Rf 0.25 (ethyl acetate: methanol = 10: 1);
[3214] _{NMR (DMSO-d 6):} δ 8.85 (d, J = 6.6Hz, 2H), 7.98 (d, J = 6.6Hz, 2H), 7.78-7.58 (m, 6H), 7.35-7.30 (m, 2H) , 5.39 (d, J = 8.5 Hz, 1H), 4.36-4.29 (m, IH), 4.19-4.13 (m, IH), 4.11 , 8.5 Hz, 1 H), 3.25-3.17 (m, 1 H), 3.11-3.02 (m, 1 H).
[3215] Example 45 (4)
[3216] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3217]
[3218] Free body:
[3219] TLC: Rf 013 (ethyl acetate);
[3220] _{NMR (DMSO-d 6):} δ 8.46 (d, J = 1.8Hz, 1H), 8.43 (dd, J = 4.8Hz, 1.8Hz, 1H), 7.86-7.54 (m, 6H), 7.42-7.30 (m , 4H), 5.43 (d, J = 7.4 Hz, 1H), 4.26-3.82, (m, 4H), 2.75 (t, J = 6.6 Hz, 2H).
[3221] Hydrochloride:
[3222] TLC: Rf 0.13 (ethyl acetate);
[3223] _{NMR (DMSO-d 6):} δ 8.88 (s, 1H), 8.80 (d, J = 5.7Hz, 1H), 8.49 (d, J = 7.8Hz, 1H), 8.04-7.92 (m, 1H), 7.78 J = 7.8 Hz, 1H), 7.24 (d, J = 8.4 Hz, 1H), 5.47 (d, J = 7.8 Hz, 1H), 4.34-4.20 (m, 1H), 4.16-3.91 (m, 3H), 3.19-2.94 (m, 2H).
[3224] Example 45 (5)
[3225] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3226]
[3227] TLC: Rf 0.17 (hexane: AcOEt = 1: 1);
[3228] _{NMR (CDCl 3): δ 7.82-7.78} (m, 2H), 7.68-7.60 (m, 1H), 7.58-7.44 (m, 3H), 7.36 (d, J = 8.0Hz, 1H), 6.86 (d, J = 8.0 Hz, 1H), 5.38 (d, J = 8.5 Hz, 1H), 4.45 (d, J = 16.2 Hz, 1H) 7.0 Hz, 2H), 4.24 (d, J = 15.0 Hz, 1H), 3.76 (dd, J = 15.0, 8.5 Hz, 1H), 1.30 (t, J = 7.0 Hz, 3H).
[3229] Example 45 (6)
[3230] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3231]
[3232] TLC: Rf 0.31 (hexane: AcOEt = 1: 1);
[3233] _{NMR (CDCl 3): δ 7.90} (d, J = 8.8Hz, 1H), 7.71-7.62 (m, 3H), 7.55-7.46 (m, 2H), 7.30 (dd, J = 8.8, 2.4Hz, 1H) , 7.02 (d, J = 2.4 Hz, 1H), 5.00 (dd, J = 7.8, 5.4 Hz, 1H), 4.67 (s, 2H), 4.28 J = 15.0, 5.4 Hz, 1H), 3.72 (dd, J = 15.0, 7.8 Hz, 1H), 1.30 (t, J = 7.2 Hz, 3H).
[3234] Example 45 (7)
[3235] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3236]
[3237] TLC: Rf 0.32 (hexane: AcOEt = 2: 1);
[3238] _{NMR (DMSO-d 6):} δ 7.81-7.75 (m, 3H), 7.68-7.60 (m, 3H), 7.53 (d, J = 2.5Hz, 1H), 7.48 (dd, J = 8.5, 2.5Hz, J = 15.0, 3.0 Hz, 1H), 5.73 (dd, J = 9.5, 3.0 Hz, 1H), 5.33 (s, 2H), 4.03 ).
[3239] Example 45 (8)
[3240] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3241]
[3242] TLC: Rf 0.35 (ethyl acetate: hexane = 1: 1);
[3243] _{NMR (CDCl 3): δ 7.73-7.61} (m, 3H), 7.58-7.45 (m, 3H), 7.44 (d, J = 2.2Hz, 1H), 7.18 (dd, J = 8.8Hz, 2.2Hz, 1H J = 7.2 Hz, 2H), 3.81-3.65 (m, 2H), 1.35 (t, J = 7.2 Hz, , 3H).
[3244] Example 45 (9)
[3245] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3246]
[3247] TLC: Rf 0.17 (ethyl acetate: hexane = 1: 1);
[3248] _{NMR (CDCl 3): δ 7.72-7.47} (m, 7H), 6.91 (d, J = 6.9Hz, 1H), 5.03 (dd, J = 8.7Hz, 5.4Hz, 1H), 4.76 (s, 2H), J = 7.2 Hz, 2H), 3.79 (dd, J = 14.7 Hz, 5.4 Hz, 1H), 3.73 (dd, J = 14.7 Hz, Hz, 3H).
[3249] Example 45 (10)
[3250] Benzyloxycarbonyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3251]
[3252] TLC: Rf 0.30 (hexane: AcOEt = 1: 1);
[3253] _{NMR (CDCl 3): δ 7.90} (d, J = 8.0Hz, 1H), 7.76-7.71 (m, 2H), 7.63-7.55 (m, 1H), 7.47-7.36 (m, 8H), 5.37 (s, J = 15.0, 1.0 Hz, 1H), 3.74 (s, 3H), 3.73 (dd, J = 15.0, 9.0 Hz, 1H) ).
[3254] Example 45 (11)
[3255] 5-ethoxycarbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3256]
[3257] TLC: Rf 0.34 (hexane: AcOEt = 1: 1);
[3258] _{NMR (DMSO-d 6):} δ 8.23 (d- type, J = 8.0Hz, 1H), 8.12 (s, 1H), 7.97 (d, J = 8.0Hz, 1H), 7.85-7.78 (m, 3H) J = 7.0 Hz, 2H), 4.10 (dd, J = 15.3, 9.3 Hz, 1H), 7.69-7.61 (m, 2H) 3.91 (dd, J = 15.3, 3.2 Hz, 1H), 1.35 (t, J = 7.0 Hz, 3H).
[3259] Example 45 (12)
[3260] Methoxycarbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3261]
[3262] TLC: Rf 0.16 (ethyl acetate: hexane = 1: 1);
[3263] _{NMR (CDCl 3): δ 8.23} (d, J = 8.1Hz, 2H), 7.81 (t, J = 8.1Hz, 1H), 7.72-7.64 (m, 3H), 7.55-7.47 (m, 2H), 5.07 (dd, J = 9.3 Hz, 4.8 Hz, 1H), 3.97 (s, 3H), 3.84 (dd, J = 14.7 Hz, 4.8 Hz, 1H) .
[3264] Example 45 (13)
[3265] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3266]
[3267] TLC: Rf 0.22 (ethyl acetate: hexane = 1: 1);
[3268] _{NMR (CDCl 3): δ 8.25} (d, J = 7.8Hz, 1H), 8.23 (d, J = 7.8Hz, 1H), 7.80 (t, J = 7.8Hz, 1H), 7.73-7.65 (m, 3H J = 7.2Hz, 2H), 3.83 (dd, J = 14.7Hz, 4.8Hz, 1H), 7.56-7.48 (m, 2H), 5.06 (dd, J = 9.3Hz, 4.8Hz, 1H) 1H), 3.73 (dd, J = 14.7 Hz, 9.3 Hz, 1H), 1.40 (t, J = 7.2 Hz, 3H).
[3269] Example 45 (14)
[3270] 5-t-butoxycarbonyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3271]
[3272] TLC: Rf 0.37 (ethyl acetate: hexane = 1: 1);
[3273] _{NMR (CDCl 3): δ 7.80} (d, J = 8.1Hz, 1H), 7.78 (d, J = 7.8Hz, 2H), 7.66 (t, J = 7.8Hz, 1H), 7.51 (t, J = 7.8 J = 9.3 Hz, 1.2 Hz, 1H), 4.14 (dd, J = 15.0 Hz, 1.2 Hz, 1H), 3.86 (s, , 3H), 3.74 (dd, J = 15.0 Hz, 9.3 Hz, 1H), 1.61 (s, 9H).
[3274] Example 45 (15)
[3275] Methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3276]
[3277] TLC: Rf 0.28 (ethyl acetate: hexane = 1: 1);
[3278] _{NMR (CDCl 3): δ 7.77-7.70} (m, 2H), 7.61 (t, J = 7.5Hz, 1H), 7.50-7.35 (m, 4H), 5.19 (dd, J = 9.3, 1.8Hz, 1H) (Dd, J = 15.0, 1.8 Hz, 1H), 4.16 (q, J = 7.2 Hz, 2H), 3.81 2.87 (m, 2H), 2.65-2.40 (m, 2H), 1.27 (t, J = 7.2 Hz, 3H).
[3279] Example 45 (16)
[3280] 3-Benzylsulfonyl-2,3-dihydro-1,1-dioxo [b] thiophene
[3281]
[3282] TLC: Rf 0.39 (hexane: AcOEt = 1: 1);
[3283] _{NMR (CDCl 3): δ 3.89} (dd, J = 15.0Hz, 9.3Hz, 1H), 3.98 (d, J = 14.0Hz, 1H), 4.03 (dd, J = 15.0Hz, 3.6Hz, 1H), 4.31 (d, J = 14.0 Hz, 1H), 4.91 (dd, J = 9.3 Hz, 3.6 Hz, 1H), 7.21-7.35 (m, 5H), 7.62-7.71 (m, 2H), 7.80-7.90 2H).
[3284] Example 45 (17)
[3285] 3- (3,4-Dichlorophenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3286]
[3287] TLC: Rf 0.43 (hexane: AcOEt = 1: 1);
[3288] _{NMR (DMSO-d 6):} δ 7.98 (d, J = 2.1Hz, 1H), 7.75-7.89 (m, 5H), 7.63 (dd, J = 8.4, 2.1Hz, 1H), 5.91 (dd, J = 8.0, 4.4 Hz, 1H), 4.04 (dd, J = 15.4, 8.0 Hz, 1H), 3.95 (dd, J = 15.4, 4.4 Hz, 1H).
[3289] Example 45 (18)
[3290] Preparation of 3- (4-nitrophenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3291]
[3292] TLC: Rf 0.33 (hexane: AcOEt = 1: 1);
[3293] _{NMR (DMSO-d 6):} δ 8.41 (d, J = 8.8Hz, 2H), 8.04 (d, J = 8.8Hz, 2H), 7.76-7.85 (m, 4H), 5.97 (dd, J = 9.0, 3.2 Hz, 1H), 4.04 (dd, J = 15.4, 9.0 Hz, 1H), 3.90 (dd, J = 15.4, 3.2 Hz, 1H).
[3294] Example 45 (19)
[3295] 5-hydroxymethyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3296]
[3297] TLC: Rf 0.51 (ethyl acetate);
[3298] _{NMR (DMSO-d 6):} δ 7.80-7.72 (m, 4H), 7.64-7.51 (m, 3H), 5.66 (dd, J = 8.5, 1.5Hz, 1H), 5.43 (t, J = 5.5Hz, (Dd, J = 15.0, 8.5 Hz, 1H), 4.00 (dd, J = 15.0, 1.5 Hz, 1H), 3.58 (s, 3H).
[3299] Example 45 (20)
[3300] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3301]
[3302] TLC: Rf 0.54 (CHCl 3: MeOH = 9: 1);
[3303] _{NMR (CDCl 3): δ 7.84} (d, J = 7.5Hz, 1H), 7.72-7.63 (m, 2H), 7.62-7.53 (m, 3H), 7.51-7.44 (m, 2H), 5.53 (d, J = 9.3 Hz, 1H), 5.08 (d, J = 13.5 Hz, 1H), 5.01 (d, J = 13.5 Hz, 1H), 3.87 15.0, 9.3 Hz, 1 H), 3.00-1.80 (br, 1 H).
[3304] Example 45 (21)
[3305] 6-Fluoro-3-phenylsulfonyl-2,3-dihydro-1,1-dioxo [b] thiophene
[3306]
[3307] TLC: Rf 0.40 (ethyl acetate: hexane = 1: 1);
[3308] _{NMR (DMSO-d 6):} δ 7.85-7.58 (m, 8H), 5.77 (dd, J = 9.6Hz, 2.7Hz, 1H), 4.07 (dd, J = 15.6Hz, 9.6Hz, 1H), 3.87 ( dd, J = 15.6 Hz, 2.7 Hz, 1H).
[3309] Example 45 (22)
[3310] 4-Fluoro-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide Beginning with benzo [b] thiophene
[3311]
[3312] TLC: Rf 0.29 (ethyl acetate: hexane = 1: 1);
[3313] _{NMR (DMSO-d 6):} δ 7.83-7.57 (m, 8H), 5.81 (dd, J = 9.0Hz, 1.5Hz, 1H), 4.09 (dd, J = 15.6Hz, 1.5Hz, 1H), 3.99 ( dd, J = 15.6 Hz, 9.0 Hz, 1H).
[3314] Example 46
[3315] 5-Methoxycarbonyl-4-ethoxybenzo [b] thiophene
[3316]
[3317] The procedure of Example 18 was repeated except that ethyl iodide was used instead of 5-methoxycarbonyl-4-hydroxybenzo [b] thiophene and 4-nitrobenzyl bromide instead of the compound prepared in Example 9 (12) , The compound of the present invention having the following physical properties was obtained.
[3318] TLC: Rf 0.44 (hexane: AcOEt = 4: 1);
[3319] _{NMR (CDCl 3): δ 7.82} (d, J = 8Hz, 1H), 7.63 (d, J = 8Hz, 1H), 7.54 (d, J = 6Hz, 1H), 7.43 (d, J = 6Hz, 1H) , 4.21 (q, J = 7 Hz, 2H), 3.95 (s, 3H), 1.49 (t, J = 7 Hz, 3H).
[3320] Example 47
[3321] 5-carboxy-4-ethoxybenzo [b] thiophene
[3322]
[3323] Methanol (10 ml) and 2N aqueous sodium hydroxide solution (5.0 ml) were added to the compound (1.11 g) prepared in Example 46, and the mixture was heated under reflux for 30 minutes. The reaction mixture was concentrated. 1N hydrochloric acid was added to the residue, acidified, and extracted with ethyl acetate. The extract was washed successively with water and saturated brine, dried over anhydrous sodium sulfate and concentrated to give the compound (1.02 g) of the present invention having the following physical data.
[3324] TLC: Rf 0.06 (hexane: AcOEt = 4: 1);
[3325] _{NMR (CDCl 3): δ 8.09} (d, J = 8Hz, 1H), 7.75 (d, J = 8Hz, 1H), 7.52 (d, J = 6Hz, 1H), 7.49 (d, J = 6Hz, 1H) , 4.44 (q, J = 7 Hz, 2H), 1.58 (t, J = 7 Hz, 3H).
[3326] Example 48
[3327] Benzyloxycarbonyl-4-ethoxybenzo [b] thiophene
[3328]
[3329] 4-carboxy-1,1-dioxide By operating in the same manner as in Example 32 using the compound prepared in Example 47 and benzyl bromide instead of benzo [b] thiophene, the title compound &Lt; / RTI &gt;
[3330] TLC: Rf 0.46 (hexane: AcOEt = 4: 1);
[3331] _{NMR (CDCl 3): δ 7.85} (d, J = 8Hz, 1H), 7.62 (d, J = 8Hz, 1H), 7.56-7.26 (m, 7H), 5.40 (s, 2H), 4.15 (q, J = 7 Hz, 2H), 1.37 (t, J = 7 Hz, 3H).
[3332] Example 49
[3333] 5-Benzyloxycarbonyl-4-ethoxy-1, 1-dioxo [b] thiophene
[3334]
[3335] The compound prepared in Example 48 was used instead of the compound prepared in Example 1, and the compound of the present invention having the following physical data was obtained in the same manner as in Example 3 except that 3- Chloro and benzoic acid were used).
[3336] TLC: Rf 0.10 (hexane: AcOEt = 4: 1);
[3337] _{NMR (CDCl 3): δ 7.99} (d, J = 8Hz, 1H), 7.60-7.30 (m, 7H), 6.72 (d, J = 7Hz, 1H), 5.38 (s, 2H), 4.03 (q, J = 7 Hz, 2H), 1.31 (t, J = 7 Hz, 3H).
[3338] Examples 50 to 50 (2)
[3339] Instead of ethyl iodide, the corresponding halide was used in the same manner as in Example 46 Example 47 Example 48 Example 49 to obtain the following compounds of the present invention.
[3340] Example 50
[3341] 5-Benzyloxycarbonyl-4-hexyloxy-1, 1-dioxo [b] thiophene
[3342]
[3343] TLC: Rf 0.22 (hexane: AcOEt = 4: 1);
[3344] _{NMR (CDCl 3): δ 7.97} (d, J = 8Hz, 1H), 7.55-7.30 (m, 7H), 6.72 (d, J = 7Hz, 1H), 5.38 (s, 2H), 3.93 (t, J = 7 Hz, 2H), 1.80-1.45 (m, 2H), 1.45-1.10 (m, 6H), 0.90 (t, J = 7 Hz, 3H).
[3345] Example 50 (1)
[3346] 5-Benzyloxycarbonyl-4-butoxy-1,1-dioxo [b] thiophene
[3347]
[3348] TLC: Rf 0.24 (hexane: AcOEt = 4: 1);
[3349] _{NMR (CDCl 3): δ 7.98} (d, J = 8Hz, 1H), 7.58-7.38 (m, 7H), 6.72 (d, J = 7Hz, 1H), 5.38 (s, 2H), 3.94 (t, J = 7 Hz, 2H), 1.78-1.50 (m, 2H), 1.50-1.20 (m, 2H), 0.92 (t, J = 7 Hz, 3H).
[3350] Example 50 (2)
[3351] 5-Benzyloxycarbonyl-4-octyloxy-1,1-dioxo [b] thiophene
[3352]
[3353] TLC: Rf 0.33 (hexane: AcOEt = 4: 1);
[3354] _{NMR (CDCl 3): δ 7.97} (d, J = 8Hz, 1H), 7.60-7.25 (m, 7H), 6.72 (d, J = 7Hz, 1H), 5.38 (s, 2H), 3.92 (t, J = 7 Hz, 2H), 1.82-1.45 (m, 2H), 1.45-1.05 (m, 10H), 0.89 (t, J = 7 Hz, 3H).
[3355] Examples 51 to 51 (3)
[3356] Using the compound prepared in Example 49 and Examples 50 to 50 (2) instead of 5-methyl-1,1-dioxide benzo [b] thiophene, the title compound Of the present invention.
[3357] Example 51
[3358] Benzyloxycarbonyl-4-ethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3359]
[3360] TLC: Rf 0.41 (chloroform: hexane: methanol = 5: 5: 1);
[3361] _{NMR (CDCl 3): δ 7.90} (d, J = 8Hz, 1H), 7.78-7.66 (m, 2H), 7.64-7.30 (m, 9H), 5.34 (s, 2H), 5.17 (d, J = 9Hz 1H), 4.30 (dd, J = 1, 15 Hz, 1H), 4.10-3.60 (m, 3H), 1.13 (t, J = 7 Hz, 3H).
[3362] Example 51 (1)
[3363] 5-Benzyloxycarbonyl-4-hexyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide Beginning with benzo [b] thiophene
[3364]
[3365] TLC: Rf 0.45 (CHCl 3: hexane: methanol = 5: 5: 1);
[3366] _{NMR (CDCl 3): δ 7.88} (d, J = 8Hz, 1H), 7.78-7.64 (m, 2H), 7.60-7.28 (m, 9H), 5.34 (s, 2H), 5.15 (d, J = 9Hz 1H), 4.32 (dd, J = 1, 15 Hz, 1H), 4.00-3.46 (m, 3H), 1.75-1.05 (m, 8H), 0.91 (t, J = 7 Hz, 3H).
[3367] Example 51 (2)
[3368] Benzyloxycarbonyl-4-butoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3369]
[3370] TLC: Rf 0.43 (chloroform: hexane: methanol = 5: 5: 1);
[3371] _{NMR (CDCl 3): δ 7.88} (d, J = 8Hz, 1H), 7.78-7.64 (m, 2H), 7.60-7.28 (m, 9H), 5.34 (s, 2H), 5.15 (d, J = 9Hz 1H), 4.32 (dd, J = 1, 15 Hz, 1H), 4.02-3.48 (m, 3H), 1.70-1.10 (m, 4H), 0.87 (t, J = 7 Hz, 3H).
[3372] Example 51 (3)
[3373] Benzyloxycarbonyl-4-octyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3374]
[3375] TLC: Rf 0.47 (CHCl 3: hexane: methanol = 5: 5: 1);
[3376] _{NMR (CDCl 3): δ 7.88} (d, J = 8Hz, 1H), 7.76-7.64 (m, 2H), 7.60-7.26 (m, 9H), 5.34 (s, 2H), 5.15 (d, J = 9Hz 1H), 4.32 (dd, J = 1, 15 Hz, 1H), 4.00-3.46 (m, 3H), 1.75-1.05 (m, 12H), 0.90 (t, J = 7 Hz, 3H).
[3377] Example 52
[3378] 5-carboxy-4-ethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3379]
[3380] The compound (670 mg) prepared in Example 51 was dissolved in ethyl acetate (50 ml), 10% palladium carbon (220 mg) was added, and the mixture was stirred at room temperature for 2 hours under a hydrogen atmosphere. The reaction mixture was filtered through celite and washed with ethyl acetate. The filtrate was concentrated. The residue was dissolved in ethyl acetate (3 ml) with heating, and hexane (5 ml) was added to crystallize. The crystals were separated by filtration and dried to obtain the compound (471 mg) of the present invention having the following physical data.
[3381] TLC: Rf 0.21 (chloroform: acetic acid = 10: 1);
[3382] NMR (CDCl ₃ + acetone _{-d 6): δ 8.02 (d} , J = 8Hz, 1H), 7.86-7.72 (m, 2H), 7.72-7.58 (m, 1H), 7.58-7.32 (m, 3H), 5.33 (d, J = 9 Hz, 1H), 4.30 (d, J = 15 Hz, 1H), 4.24-4.06 (m, 1H), 4.20 (bs, 1H) 74 (m, 2H), 1.25 (t, J = 7 Hz, 3H).
[3383] Examples 52 (1) to 52 (3)
[3384] The following compounds were obtained in the same manner as in Example 52 using the compounds prepared in Examples 51 (1) to 51 (3) instead of the compounds prepared in Example 51.
[3385] Example 52 (1)
[3386] 5-carboxy-4-hexyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3387]
[3388] TLC: Rf 0.38 (chloroform: acetic acid = 10: 1);
[3389] NMR (CDCl ₃ + acetone-d ₆ ): 隆 8.00 (d, J = 8 Hz, 1H), 7.88-7.72 (m, 2H), 7.72-7.56 (m, 1H), 7.56-7.34 J = 7.9 Hz, 1H), 4.02-3.66 (m, 1H), 4.32 (d, J = 2H), 1.80-1.45 (m, 2H), 1.45-1.12 (m, 6H), 0.91 (t, J = 7 Hz, 3H).
[3390] Example 52 (2)
[3391] 5-carboxy-4-butoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3392]
[3393] TLC: Rf 0.34 (chloroform: acetic acid = 10: 1);
[3394] NMR (CDCl ₃ + acetone _{-d 6): δ 8.00 (d} , J = 8Hz, 1H), 7.86-7.72 (m, 2H), 7.72-7.56 (m, 1H), 7.56-7.34 (m, 3H), J = 7.9 Hz, 1H), 4.31 (dd, J = 1.15 Hz, 1H), 4.20 (brs, 2H), 1.74-1.48 (m, 2H), 1.48-1.20 (m, 2H), 0.92 (t, J = 7 Hz, 3H).
[3395] Example 52 (3)
[3396] 5-carboxy-4-octyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3397]
[3398] TLC: Rf 0.40 (chloroform: acetic acid = 10: 1);
[3399] NMR (CDCl ₃ + acetone-d ₆ ): 隆 8.00 (d, J = 8 Hz, 1H), 7.84-7.72 (m, 2H), 7.72-7.57 (m, 1H), 7.57-7.34 (Dd, J = 9 Hz, 1H), 4.31 (dd, J = 1, 15 Hz, 1H), 4.13 2H), 1.74-1.43 (m, 2H), 1.43-1.05 (m, 10H), 0.90 (t, J = 7 Hz, 3H).
[3400] Examples 53 to 53 (3)
[3401] Instead of the compound prepared in Examples 52 to 52 (3) and 1- (3-hydroxypropyl) pyrrole in place of 4-hydroxy-1,1-dioxide benzo [b] thiophene The procedure of Example 32 was repeated to give the compound of the present invention as shown below.
[3402] Example 53
[3403] Methoxycarbonyl-4-ethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3404]
[3405] TLC: Rf 0.35 (chloroform: hexane: methanol = 5: 5: 1);
[3406] _{NMR (CDCl 3): δ 7.91} (d, J = 8Hz, 1H), 7.84-7.72 (m, 2H), 7.72-7.57 (m, 1H), 7.57-7.32 (m, 3H), 5.21 (d, J = 9 Hz, 1H), 4.28 (dd, J = 1, 15 Hz, 1H), 4.20-4.00 (m, 1H), 3.93 (s, 3H), 3.95-3.68 7Hz, 3H).
[3407] Example 53 (1)
[3408] 5-Methoxycarbonyl-4-hexyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3409]
[3410] TLC: Rf 0.42 (CHCl 3: hexane: methanol = 5: 5: 1);
[3411] _{NMR (CDCl 3): δ 7.89} (d, J = 8Hz, 1H), 7.82-7.69 (m, 2H), 7.69-7.55 (m, 1H), 7.55-7.30 (m, 3H), 5.19 (d, J (D, J = 7.9 Hz, 1H), 4.30 (d, J = 15 Hz, 1H), 4.08 m, 2H), 1.46-1.15 (m, 6H), 0.92 (t, J = 7 Hz, 3H).
[3412] Example 53 (2)
[3413] Methoxycarbonyl-4-butoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3414]
[3415] TLC: Rf 0.37 (CHCl 3: hexane: methanol = 5: 5: 1);
[3416] _{NMR (CDCl 3): δ 7.89} (d, J = 8Hz, 1H), 7.82-7.68 (m, 2H), 7.68-7.55 (m, 1H), 7.55-7.34 (m, 3H), 5.19 (d, J (M, 2H), 1.80 (d, J = 7 Hz, 1H), 4.31 (dd, J = 1.50 (m, 2H), 1.50-1.18 (m, 2H), 0.94 (t, J = 7 Hz, 3H).
[3417] Example 53 (3)
[3418] 5-Methoxycarbonyl-4-octyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3419]
[3420] TLC: Rf 0.44 (chloroform: hexane: methanol = 5: 5: 1);
[3421] NMR (CDCl ₃ ): 7.89 (d, J = 8 Hz, 1H), 7.80-7.69 (m, 2H), 7.69-7.55 (m, 1H), 7.55-7.34 1H), 4.30 (dd, J = 1, 15 Hz, 1H), 4.06 (dt, J = 7.9 Hz, 1H), 3.93 (s, 3H), 3.90-3.58 1.45 (m, 2H), 1.45-1.10 (m, 10H), 0.90 (t, J = 7 Hz, 3H).
[3422] Examples 54 to 54 (19)
[3423] Using the compound prepared in Examples 52 to 52 (3) and an amine derivative corresponding to (pyridin-3-ylmethyl) amine instead of 4-carboxy-1,1-dioxide benzo [b] thiophene, , The following compounds of the present invention were obtained.
[3424] Example 54
[3425] Ethyl) piperazin-1-yl) carbonyl-4-ethoxy-3-phenylsulfonyl-2,3-dihydro- Dioxo [b] thiophene
[3426]
[3427] TLC: Rf 0.73 (CHCl 3: MeOH = 5: 1);
[3428] _{NMR (CDCl 3): δ 7.90} (d, J = 8Hz, 1H), 7.78-7.15 (m, 10H), 5.33 and 5.19 (each d, J = 9Hz, total 1H), 4.40-3.50 (m, 6H ) , 3.40-2.25 (m, 10H), 1.30-1. 10 (m, 3H).
[3429] Example 54 (1)
[3430] 1-yl) carbonyl-4-ethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3431]
[3432] TLC: Rf 0.75 (CHCl 3: MeOH = 5: 1);
[3433] _{NMR (CDCl 3): δ 7.90} (d, J = 8Hz, 1H), 7.80-6.85 (m, 10H), 5.33 and 5.21 (each d, J = 9Hz, total 1H), 4.45-3.55 (m, 6H ) , 3.50-2.80 (m, 6H), 1.25 (t, J = 7 Hz, 3H).
[3434] Example 54 (2)
[3435] Carbamoyl-4-ethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3436]
[3437] TLC: Rf 0.34 (CHCl 3: MeOH = 5: 1);
[3438] NMR (CDCl _3): δ 8.24 and 8.11 (each d, J = 8Hz, total 1H), 8.00-7.15 (m, 7H ), 5.15 (d, J = 9Hz, 1H), 4.50-3.30 (m, 6H) , 2.54 (t, J = 7 Hz, 2H), 2.32 (s, 6H), 1.45-1.20 (m, 3H).
[3439] Example 54 (3)
[3440] (2,3,4,5,6,7-hexahydro-1H-azepin-1-yl) carbonyl-4-ethoxy-3-phenylsulfonyl-2,3-dihydro- 1-dioxide benzo [b] thiophene
[3441]
[3442] TLC: Rf 0.19 (ethyl acetate: hexane = 2: 1);
[3443] _{NMR (CDCl 3): δ 7.87} (d, J = 8Hz, 1H), 7.80-7.20 (m, 6H), 5.32 and 5.20 (each d, J = 9Hz, total 1H), 4.40-2.90 (m, 8H ) , 2.10-1.00 (m, 11 H).
[3444] Example 54 (4)
[3445] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3446]
[3447] TLC: Rf 0.40 (ethyl acetate: hexane = 2: 1);
[3448] NMR (CDCl ₃ ): 8.29 (d, J = 8 Hz, 1H), 8.05-6.90 (m, 10H), 5.38-5.10 (m, 1H), 4.50-3.40 = 8 Hz, 2H), 1.40-1.00 (m, 3H).
[3449] Example 54 (5)
[3450] 1-yl) carbonyl-4-hexyloxy-3-phenylsulfonyl-2,3-dihydro-1,1 - &lt; / RTI &gt; dioxo [b] thiophene
[3451]
[3452] TLC: Rf 0.57 (CHCl 3: MeOH = 10: 1);
[3453] _{NMR (CDCl 3): δ 7.89} (d, J = 8Hz, 1H), 7.76-7.20 (m, 10H), 5.30 and 5.17 (each d, J = 9Hz, total 1H), 4.25 (d, J = 15Hz, 1H), 4.20-3.50 (m, 5H), 3.50-2.80 (m, 4H), 2.80-2.20 (m, 6H), 1.90-1.05 (m, 8H), 0.90 (t, J = 7Hz, 3H).
[3454] Example 54 (6)
[3455] Yl) carbonyl-4-hexyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene Offen
[3456]
[3457] TLC: Rf 0.66 (CHCl 3: MeOH = 10: 1);
[3458] _{NMR (DMSO-d 6):} δ 8.31 (s, 1H), 8.00-6.95 (m, 10H), 5.66 (d, J = 9Hz, 1H), 4.32 (d, J = 15Hz, 1H), 4.22-2.70 (m, 11H), 1.60-1.02 (m, 8H), 0.87 (t, J = 7 Hz, 3H).
[3459] Example 54 (7)
[3460] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene (2-dimethylaminoethyl) carbamoyl-
[3461]
[3462] TLC: Rf 0.23 (CHCl 3: MeOH = 10: 1);
[3463] NMR (CDCl _3): δ 8.21 and 8.07 (each d, J = 8Hz, total 1H), 7.90-7.10 (m, 7H ), 5.13 (d, J = 9Hz, 1H), 4.32 (d, J = 15Hz, (T, J = 6 Hz, total 2H), 2.33 (s, 6H), 2.05-1.10 (m, 8H), 0.92 , 3H).
[3464] Example 54 (8)
[3465] 5- (2,3,4,5,6,7-hexahydro-1H-azepin-1-yl) carbonyl-4-hexyloxy-3-phenylsulfonyl-2,3-dihydro- , 1-dioxide benzo [b] thiophene
[3466]
[3467] TLC: Rf 0.23 (hexane: AcOEt = 1: 1);
[3468] _{NMR (CDCl 3): δ 7.86} (d, J = 8Hz, 1H), 7.78-7.20 (m, 6H), 5.30 and 5.18 (each d, J = 9Hz, total 1H), 4.25 (d, J = 15Hz, 1H), 4.35-3.00 (m, 7H), 2.10-1.10 (m, 16H), 0.91 (t, J = 7 Hz, 3H).
[3469] Example 54 (9)
[3470] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3471]
[3472] TLC: Rf 0.39 (hexane: AcOEt = 1: 1);
[3473] _{NMR (CDCl 3): δ 8.29} (d, J = 8Hz, 1H), 8.10-6.80 (m, 10H), 5.40-5.05 (m, 1H), 4.50-3.35 (m, 6H), 3.16 (t, J = 8 Hz, 2H), 1.90-0.95 (m, 8H), 0.95-0.75 (m, 3H).
[3474] Example 54 (10)
[3475] 1-yl) carbonyl-4-butoxy-3-phenylsulfonyl-2,3-dihydro-1,1- Dioxo [b] thiophene
[3476]
[3477] TLC: Rf 0.56 (CHCl 3: MeOH = 10: 1);
[3478] NMR (CDCl ₃ ): 7.88 (d, J = 8 Hz, 1H), 7.80-7.00 (m, 10H), 5.30 and 5.18 (d, J = 9Hz, total 1H), 4.40-3.45 , 3.45-2.80 (m, 4H), 2.80-2.15 (m, 6H), 2.00-1.10 (m, 4H), 0.97 and 0.91 (e ach t, J = 7 Hz, total 3H).
[3479] Example 54 (11)
[3480] 1-yl) carbonyl-4-butoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3481]
[3482] TLC: Rf 0.65 (CHCl 3: MeOH = 10: 1);
[3483] _{NMR (CDCl 3): δ 7.89} (d, J = 8Hz, 1H), 7.80-7.17 (m, 8H), 7.17-6.85 (m, 2H), 5.31 and 5.19 (each d, J = 9Hz, total 1H) , 4.40-3.55 (m, 6H), 3.55-2.70 (m, 6H), 2.00-1.15 (m, 4H), 0.99 and 0.94 (t, J = 7 Hz, total 3H).
[3484] Example 54 (12)
[3485] Carbamoyl-4-butoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3486]
[3487] TLC: Rf 0.21 (CHCl 3: MeOH = 10: 1);
[3488] _{NMR (CDCl 3): δ 8.08} (d, J = 8Hz, 1H), 7.85-7.35 (m, 6H), 7.25 (broad peak, 1H), 5.13 (d, J = 9Hz, 1H), 4.32 (d, J = 15 Hz, 1H), 4.05-3.66 (m, 3H), 3.66-3.35 (m, 2H), 2.52 4H), 0.96 (t, J = 7 Hz, 3H).
[3489] Example 54 (13)
[3490] (2,3,4,5,6,7-hexahydro-1H-azepin-1-yl) carbonyl-4-butoxy-3-phenylsulfonyl- 1-dioxide benzo [b] thiophene
[3491]
[3492] TLC: Rf 0.19 (ethyl acetate: hexane = 1: 1);
[3493] _{NMR (CDCl 3): δ 7.85} (d, J = 8Hz, 1H), 7.76-7.20 (m, 6H), 5.29 and 5.18 (each d, J = 9Hz, total 1H), 4.25 (d, J = 15Hz, 1H), 4.25-3.60 (m, 4H), 3.60-3.00 (m, 3H), 2.10-1.10 (m, 12H), 0.96 and 0.92 (t, J = 7Hz, total 3H).
[3494] Example 54 (14)
[3495] Benzo [b] thiophene &lt; / RTI &gt; &lt; RTI ID = 0.0 &
[3496]
[3497] TLC: Rf 0.31 (ethyl acetate: hexane = 1: 1);
[3498] _{NMR (CDCl 3): δ 8.29} (d, J = 8Hz, 1H), 8.05-7.42 (m, 6H), 7.42-6.95 (m, 4H), 5.36-5.06 (m, 1H), 4.50-3.40 (m , 6H), 3.16 (t, J = 7 Hz), 1.90-1.05 (m, 4H), 0.81 (t, J = 7 Hz, 3H).
[3499] Example 54 (15)
[3500] 1-yl) carbonyl-4-octyloxy-3-phenylsulfonyl-2,3-dihydro-1,1- Dioxo [b] thiophene
[3501]
[3502] TLC: Rf 0.66 (CHCl 3: MeOH = 10: 1);
[3503] _{NMR (CDCl 3): δ 7.89} (d, J = 8Hz, 1H), 7.80-7.20 (m, 10H), 5.30 and 5.17 (each d, J = 9Hz, total 1H), 4.25 (d, J = 15Hz, 1H), 4.30-3.55 (m, 5H), 3.55-2.80 (m, 4H), 2.80-2.25 (m, 6H), 1.90-1.05 (m, 12H), 0.88 (t, J = 7Hz, 3H).
[3504] Example 54 (16)
[3505] 1-yl) carbonyl-4-octyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3506]
[3507] TLC: Rf 0.74 (CHCl 3: MeOH = 10: 1);
[3508] _{NMR (CDCl 3): δ 7.89} (d, J = 8Hz, 1H), 7.82-6.85 (m, 10H), 5.31 and 5.19 (each d, J = 9Hz, total 1H), 4.38-2.70 (m, 12H ) , 1.90-1.05 (m, 12H), 0.89 (t, J = 7 Hz, 3H).
[3509] Example 54 (17)
[3510] Carbamoyl-4-octyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3511]
[3512] TLC: Rf 0.34 (CHCl 3: MeOH = 10: 1);
[3513] _{NMR (CDCl 3): δ 7.99} (d, J = 8Hz, 1H), 7.92-7.10 (m, 7H), 5.30-5.00 (m, 1H), 4.40-3.45 (m, 6H), 2.70 (t, J = 6 Hz, 2H), 2.46 (s, 6H), 1.95-1.05 (m, 12H), 0.90 (t, J = 7 Hz, 3H).
[3514] Example 54 (18)
[3515] 5- (2,3,4,5,6,7-hexahydro-1H-azepin-1-yl) carbonyl-4-octyloxy-3-phenylsulfonyl-2,3-dihydro- 1-dioxide benzo [b] thiophene
[3516]
[3517] TLC: Rf 0.26 (hexane: AcOEt = 1: 1);
[3518] _{NMR (CDCl 3): δ 7.85} (d, J = 8Hz, 1H), 7.88-7.15 (m, 6H), 5.29 and 5.18 (each d, J = 9Hz, total 1H), 4.40-3.00 (m, 8H ) , 2.10-1.05 (m, 20H), 0.90 (t, J = 7 Hz, 3H).
[3519] Example 54 (19)
[3520] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3521]
[3522] TLC: Rf 0.43 (hexane: AcOEt = 1: 1);
[3523] NMR (CDCl ₃ ): 8.29 (d, J = 8 Hz, 1H), 8.10-6.80 (m, 10H), 5.40-5.05 (m, 1H), 4.60-3.40 = 8 Hz, 2H), 1.90-1.00 (m, 12H), 0.85 (t, J = 7 Hz, 3H).
[3524] Example 55
[3525] 5-hydroxy-4-formylbenzo [b] thiophene
[3526]
[3527] Dichloromethyl methyl ether (4.52 ml) and titanium tetrachloride (5.48 ml) were added dropwise to a methylene chloride (60 ml) solution of 5-hydroxybenzo [b] thiophene (3.0 g) at 0 ° C and the mixture was stirred at room temperature for 30 minutes . Ice water was added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was purified by silica gel column chromatography (methylene chloride) to give the present compound (1.50 g) having the following physical data.
[3528] TLC: Rf 0.69 (hexane: AcOEt = 2: 1);
[3529] _{NMR (CDCl 3): δ 11.97} (s, 1H), 10.55 (s, 1H), 7.96 (d, J = 8.8Hz, 1H), 7.77 (d, J = 5.6Hz, 1H), 7.72 (d, J = 5.6 Hz, 1 H), 7.02 (d, J = 8.8 Hz, 1 H).
[3530] Example 56
[3531] 5-Benzyloxy-4-formylbenzo [b] thiophene
[3532]
[3533] The procedure of Example 18 was repeated except that the compound prepared in Example 55 and benzyl bromide were used instead of the compound prepared in Example 55 and 4-nitrobenzyl bromide to obtain the title compound having the following physical data To obtain a compound of the present invention.
[3534] TLC: Rf 0.65 (hexane: AcOEt = 2: 1);
[3535] _{NMR (CDCl 3): δ 10.81} (s, 1H), 8.43 (d, J = 5.6Hz, 1H), 8.00 (d, J = 8.8Hz, 1H), 7.68 (d, J = 5.6Hz, 1H), 7.55-7.30 (m, 5H), 7.15 (d, J = 8.8 Hz, 1H), 5.28 (s, 2H).
[3536] Example 57
[3537] 5-Benzyloxy-4-hydroxymethylbenzo [b] thiophene
[3538]
[3539] Sodium borohydride (246 mg) and methanol (3.0 ml) were added to a methylene chloride (9.0 ml) solution of the compound (1.24 g) prepared in Example 56 and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was diluted with 1N hydrochloric acid and extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was purified by silica gel column chromatography (hexane: ethyl acetate = 4: 1) to obtain the compound (1.25 g) of the present invention having the following physical data.
[3540] TLC: Rf 0.40 (hexane: AcOEt = 2: 1);
[3541] _{NMR (CDCl 3): δ 7.76} (d, J = 8.8Hz, 1H), 7.54-7.28 (m, 7H), 7.12 (d, J = 8.8Hz, 1H), 5.20 (s, 2H), 5.04 (br -s, 2H), 2.30-2.12 (br, IH).
[3542] Example 58
[3543] 5-Benzyloxy-4-hydroxymethyl-1, 1-dioxo [b] thiophene
[3544]
[3545] The compound prepared in Example 57 was used instead of the compound prepared in Example 1, and the compound of the present invention having the following physical data was obtained in the same manner as in Example 3 except that 3- Chloro and benzoic acid were used).
[3546] TLC: Rf 0.43 (hexane: AcOEt = 1: 1);
[3547] _{NMR (CDCl 3): δ 7.61} (d, J = 7.0Hz, 1H), 7.56 (d, J = 7.0Hz, 1H), 7.48-7.34 (m, 5H), 7.02 (d, J = 8.4Hz, 1H ), 6.75 (d, J = 7.0 Hz, IH), 5.18 (s, 2H), 4.84 (brs, 2H), 2.26-2.10 (br, IH).
[3548] Example 59
[3549] 5-Benzyloxy-4-hydroxymethyl-3-phenylthio-2,3-dihydro-1,1-dioxo [b] thiophene
[3550]
[3551] 1,1-dioxo [theta] benzo [b] thiophene and thiophenol were used in the same manner as in Example 1 to obtain the compounds of the present invention having the following physical data.
[3552] TLC: Rf 0.60 (chloroform: ethyl acetate = 19: 1);
[3553] NMR (CDCl ₃ ): 7.67 (d, J = 8.4 Hz, 1H), 7.57-7.48 (m, 2H), 7.46-7.32 J = 6.6, 1.8 Hz, 1H), 4.99 (d, J = 6.0 Hz, 2H), 3.71 (dd, J = 14.0, 6.6 Hz, 1H), 3.59 (dd, J = 14.0, 1.8 Hz, 1H), 2.59 (t, J = 6.0 Hz, 1H).
[3554] Example 60
[3555] 5-Benzyloxy-4-bromomethyl-3-phenylthio-2,3-dihydro-1,1-dioxo [
[3556]
[3557] Triphenylphosphine (1.38 g) was added to a methylene chloride (15 ml) solution of the compound (1.45 g) prepared in Example 59, carbon tetrabromide (1.74 g) was added and the mixture was stirred at room temperature for 30 minutes. The reaction mixture was concentrated. The residue was purified by silica gel column chromatography (hexane: ethyl acetate = 2: 1) to obtain the present compound (1.62 g) having the following physical data.
[3558] TLC: Rf 0.76 (hexane: AcOEt = 1: 1);
[3559] _{NMR (CDCl 3): δ 7.66} (d, J = 8.8Hz, 1H), 7.60-7.51 (m, 2H), 7.50-7.30 (m, 8H), 7.12 (d, J = 8.8Hz, 1H), 5.27 (s, 2H), 5.15 (dd, J = 6.8, 1.6 Hz, 1H), 5.02 (d, J = 10 Hz, 1H), 4.94 6.8 Hz, 1H), 3.60 (dd, J = 13.8, 1.6 Hz, 1H).
[3560] Example 61
[3561] 5-Benzyloxy-4-aminomethyl-3-phenylthio-2,3-dihydro-1,1-dioxo [
[3562]
[3563] A tetrahydrofuran (30 ml) solution of the compound (1.60 g) prepared in Example 60 and potassium carbonate (700 mg) were successively added to a tetrahydrofuran (30 ml) solution of 28% aqueous ammonia solution (6.75 ml) Lt; / RTI &gt; for 1.5 hours. The reaction mixture was concentrated. The residue was purified by silica gel column chromatography (chloroform: methanol = 20: 1) to obtain the present compound (747 mg) having the following physical data.
[3564] TLC: Rf 0.05 (hexane: AcOEt = 1: 1);
[3565] _{NMR (CDCl 3): δ 7.63} (d, J = 8.5Hz, 1H), 7.58-7.48 (m, 2H), 7.46-7.28 (m, 8H), 7.14 (d, J = 8.5Hz, 1H), 5.23 (s, 2H), 5.13 (dd, J = 6.4,1.6 Hz, 1H), 4.12 (d, J = 13.6 Hz, 1H), 4.02 14.0, 6.0 Hz, 1 H), 3.59 (dd, J = 14.0, 1.6 Hz, 1 H).
[3566] Example 62
[3567] Benzyloxy-4-t-butoxycarbonylaminomethyl-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3568]
[3569] The compound (735 mg) prepared in Example 61 was dissolved in tetrahydrofuran (12 ml) and water (3.0 ml), sodium hydrogen carbonate (165 mg) and di-t-butyl dicarbonate (430 Mg), which was stirred for 1 hour at room temperature. Water was added to the reaction mixture and extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was purified by silica gel column chromatography (hexane: ethyl acetate = 2: 1) to obtain the present compound (867 mg) having the following physical data.
[3570] TLC: Rf 0.73 (hexane: AcOEt = 1: 1);
[3571] _{NMR (CDCl 3): δ 7.70-7.56} (m, 3H), 7.48-7.30 (m, 8H), 7.12 (d, J = 8.8Hz, 1H), 5.66 (br-d, J = 5.8Hz, 1H) (D, J = 14.0, 6.8 Hz, 1H), 3.56 (d, J = 14.0 Hz, 1H), 5.22 (s, 2H), 5.20-4.88 ), 1.41 (s, 9H).
[3572] Example 63
[3573] Benzyloxy-4-t-butoxycarbonylaminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3574]
[3575] The compound prepared in Example 62 was used instead of the compound prepared in Example 1, and the compound of the present invention having the following physical data was obtained in the same manner as in Example 3 except that 3- Chloro and benzoic acid were used).
[3576] TLC: Rf 0.31 (hexane: AcOEt = 2: 1);
[3577] _{NMR (CDCl 3): δ 7.83-7.76} (m, 2H), 7.71-7.64 (m, 1H), 7.60 (d, J = 8.7Hz, 1H), 7.56-7.38 (m, 7H), 7.19 (d, 1H, J = 8.7 Hz, 1H), 6.05 (brd, J = 6.9 Hz, 1H), 5.27-5.15 (m, 1H), 5.25 (s, 2H), 5.10-4.95 (Dd, J = 15.3, 2.1 Hz, 1H), 3.74 (dd, J = 15.3, 8.1, 1H), 1.37 (s, 9H).
[3578] Example 64
[3579] Benzyloxy-4-aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene hydrochloride
[3580]
[3581] The compound prepared in Example 63 was used in place of the compound prepared in Example 6 (8) to give the compound of the present invention having the following physical data.
[3582] TLC: Rf 0.43 (CHCl 3: MeOH = 9: 1);
[3583] _{NMR (DMSO-d 6):} δ 8.18 (brs, 3H), 7.86 (d, J = 9.0Hz, 1H), 7.83-7.75 (m, 3H), 7.67-7.48 (m, 5H), 7.47-7.33 ( J = 12.3 Hz, 1H), 5.43 (d, J = 12.3 Hz, 1H), 4.44 (d, J = Hz, 1H), 4.24 (d, J = 13.8 Hz, 1H), 3.90-3.76 (m, 2H).
[3584] Example 65
[3585] 5-hydroxy-4-t-butoxycarbonylaminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3586]
[3587] The compound prepared in Example 63 was used instead of the compound prepared in Example 51, and the procedure of Example 52 was followed to obtain the compound of the present invention having the following physical data.
[3588] TLC: Rf 0.22 (hexane: AcOEt = 1: 1);
[3589] _{NMR (CDCl 3): δ 10.75} (s, 1H), 7.75-7.58 (m, 3H), 7.56-7.41 (m, 3H), 7.18 (d, J = 8.6Hz, 1H), 6.35-6.50 (m, 1H), 5.24-5.15 (m, 1H), 4.76-4.60 (m, 1H), 4.34 (dd, J = 16.0,5.4Hz, 1H), 3.86-3.66 .
[3590] Examples 66 to 66 (1)
[3591] Hydroxy-1,1-dioxide By using the compound prepared in Example 65 and 1- (3-hydroxypropyl) pyrrole in place of the benzo [b] thiophene in accordance with the method of Example 29 The following compounds of the present invention were obtained.
[3592] Example 66
[3593] Methoxy-4-t-butoxycarbonylaminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3594]
[3595] TLC: Rf 0.28 (hexane: AcOEt = 1: 1);
[3596] _{NMR (CDCl 3): δ 7.86-7.75} (m, 2H), 7.74-7.47 (m, 4H), 7.14 (d, J = 8.8Hz, 1H), 6.10-6.00 (m, 1H), 5.32-5.18 ( m, 1 H), 5.10-4.92 (m, 1 H), 4.25-4.10 (m, 1 H), 4.00 (s, 3H), 3.85-3.65 (m,
[3597] Example 66 (1)
[3598] 4-t-butoxycarbonylaminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3599]
[3600] TLC: Rf 0.51 (hexane: AcOEt = 1: 1);
[3601] _{NMR (CDCl 3): δ 7.87-7.73} (m, 2H), 7.73-7.40 (m, 6H), 7.40-7.16 (m, 3H), 7.07 (d, J = 8.8Hz, 1H), 6.55-6.30 ( (m, IH), 6.07-5.95 (m, IH), 5.26-5.12 (m, IH), 5.10-4.90 (m, 2.86 (t, J = 7.0 Hz, 2H), 2.33-2.15 (m, 2H), 1.38 (s, 9H).
[3602] Examples 67 to 67 (1)
[3603] The compound of the present invention shown below was obtained by following the procedure of Example 7 while using the compound prepared in Example 66 (1) instead of the compound prepared in Example 6 (8).
[3604] Example 67
[3605] 5-Methoxy-4-aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene hydrochloride
[3606]
[3607] TLC: Rf 0.19 (CHCl 3: MeOH = 4: 1);
[3608] _{NMR (DMSO-d 6):} δ 8.19 (brs, 3H), 7.89-7.76 (m, 4H), 7.68-7.60 (m, 2H), 7.47 (d, J = 8.7Hz, 1H), 6.39 (t, J = 5.4 Hz, 1H), 4.47-4.28 (br, IH), 4.25-4.08 (br, IH), 3.98 (s, 3H), 3.82 (d, J = 5.4 Hz, 2H).
[3609] Example 67 (1)
[3610] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene hydrochloride
[3611]
[3612] TLC: Rf 0.43 (CHCl 3: MeOH = 9: 1);
[3613] _{NMR (DMSO-d 6):} δ 8.14 (brs, 3H), 7.86-7.76 (m, 4H), 7.68-7.61 (m, 2H), 7.45 (d, J = 8.7Hz, 1H), 7.34-7.27 ( 2H), 2.86-2.73 (m, 2H), 2.86-2.73 (m, 2H) 2. 22-2. 08 (m, 2H).
[3614] Example 68
[3615] Benzyloxy-4-hydroxymethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3616]
[3617] The compound prepared in Example 59 was used instead of the compound prepared in Example 1, and the compound of the present invention having the following physical properties was obtained in the same manner as in Example 3 except that 3- Chloro and benzoic acid were used).
[3618] TLC: Rf 0.25 (hexane: AcOEt = 1: 1);
[3619] _{NMR (CDCl 3): δ 7.72-7.58} (m, 3H), 7.56-7.30 (m, 8H), 7.20 (d, J = 8.8Hz, 1H), 5.53 (dd, J = 8.4, 1.8Hz, 1H) , 5.33 (d, J = 11.8 Hz, 1H), 5.25 (d, J = 11.8 Hz, 1H), 5.10-5.01 (m, 2H), 3.87 dd, J = 15.4, 1.8 Hz, 1H), 3.40-3.28 (m, 1H).
[3620] Example 69
[3621] Benzyloxy-4-carboxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3622]
[3623] Pyridinium dichromate (564 mg) and magnesium sulfate (500 mg) were added to a methylene chloride (10 ml) solution of the compound (444 mg) prepared in Example 68 and the mixture was stirred at room temperature for 6 hours. Insolubles were filtered off and discarded. The filtrate was added to 1N hydrochloric acid and extracted with methylene chloride. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was washed with methanol and dried. This solid was dissolved in dimethylformamide (16 ml) and water (4.0 ml), and 2-methyl-2-butene (0.48 ml), sodium dihydrogenphosphate (120 mg) and sodium chlorite (358 mg) And the mixture was stirred at room temperature for 1 hour. The reaction mixture was added to 0.5 N hydrochloric acid, extracted with ethyl acetate, and the extract was concentrated. The residue was washed with ether to obtain the compound (305 mg) of the present invention having the following physical properties.
[3624] TLC: Rf 0.17 (CHCl 3: MeOH = 9: 1);
[3625] NMR (DMSO-d ₆ ): 13.52 (s, 1H), 7.92-7.68 (m, 4H), 7.67-7.30 (m, 8H), 5.88 2H), 4.09 (dd, J = 15.0, 9.0 Hz, 1H), 3.88 (d, J = 15.0 Hz, 1H).
[3626] Example 70
[3627] Benzyloxy-4- (pyridin-3-ylmethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3628]
[3629] 4-carboxy-1,1-dioxide By operating in the same manner as in Example 28 using the compound prepared in Example 69 and (pyridin-3-ylmethyl) amine instead of benzo [b] thiophene, The inventive compound was obtained.
[3630] TLC: Rf 0.53 (CHCl 3: MeOH = 9: 1);
[3631] _{NMR (DMSO-d 6):} δ 9.05 (t, J = 6.0Hz, 1H), 8.59 (d, J = 1.5Hz, 1H), 8.41 (dd, J = 4.8, 1.5Hz, 1H), 7.85 (d 2H), 7.38-7.30 (m, 3H), 7.15 (dd, J), 7.8-7. = 8.1, 4.8 Hz, 1H), 5.96 (d, J = 9.0 Hz, 1H), 5.29 (s, 2H), 4.63 (dd, J = 15.0, 6.0 Hz, 1H) 6.0 Hz, 1H), 4.06 (dd, J = 15.0, 9.0 Hz, 1H), 3.87 (d, J = 15.0 Hz, 1H).
[3632] Example 71
[3633] 3-ylmethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[3634]
[3635] The compound prepared in Example 70 was used instead of the compound prepared in Example 51, and the procedure of Example 52 was followed to obtain the compound of the present invention having the following physical data.
[3636] TLC: Rf 0.29 (CHCl 3: MeOH = 9: 1);
[3637] _{NMR (DMSO-d 6):} δ 11.70 (br, 1H), 9.10-8.90 (br, 1H), 8.66 (d, 1H), 8.44 (dd, 1H), 7.88-7.81 (m, 1H), 7.78- 7.34 (dd, J = 7.5, 4.8 Hz, 1H), 7.23 (d, J = 8.7 Hz, 1H), 6.14 (d, J = 9.0Hz, 1H), 7.68 (m, 3H), 7.67-7.54 (Dd, J = 15.3, 6.3 Hz, 1H), 4.39 (dd, J = 15.3, 5.4 Hz, 1H), 4.02 J = 15.0 Hz, 1H).
[3638] Examples 72 to 72 (31)
[3639] The same procedure as in Example 28 was carried out using carboxylic acid corresponding to 4-carboxy-1,1-dioxide benzo [b] thiophene and amine derivative corresponding to (pyridin-3-ylmethyl) amine And, if necessary, converted into the corresponding salt by a known method to obtain the compound of the present invention shown below.
[3640] Further, in the preparation of the compound of Example 72 (9), 5-carboxy-4-methoxy-1,1-dioxide benzo [b] thiophene and 6-dimethylaminohexanol were used.
[3641] Example 72
[3642] 4- (1,1-Dimethyl-2-hydroxyethyl) carbamoyl-1,1-dioxide benzo [b] thiophene
[3643]
[3644] TLC: Rf 0.64 (ethyl acetate);
[3645] _{NMR (DMSO-d 6):} δ 8.05 (brs, 1H), 7.91 (d, J = 7.4Hz, 1H), 7.76 (d, J = 7.0Hz, 1H), 7.75 (d, J = 7.4Hz, 1H ), 7.63 (t, J = 7.4 Hz, 1H), 7.43 (d, J = 7.0 Hz, 1H) 1.29 (s, 6 H).
[3646] Example 72 (1)
[3647] 4- (2-hydroxyethyl) carbamoyl-l, l-dioxide benzo [b] thiophene
[3648]
[3649] TLC: Rf 0.30 (ethyl acetate);
[3650] _{NMR (DMSO-d 6):} δ 8.72 (t, J = 5.6Hz, 1H), 7.95 (d, J = 7.4Hz, 1H), 7.88-7.80 (m, 2H), 7.66 (t, J = 7.4Hz J = 5.6 Hz, 2H), 3.33 (q, J = 5.6 Hz, 2H), 7.45 (d, J = 7.0 Hz, 1H) ).
[3651] Example 72 (2)
[3652] (4- (2-hydroxyethyl) piperazin-1-yl) carbonyl-1,1-dioxide benzo [b] thiophene
[3653]
[3654] TLC: Rf 0.45 (ethyl acetate: methanol = 9: 1);
[3655] _{NMR (CDCl 3): δ 7.76} (d, J = 7.5Hz, 1H), 7.57 (t, J = 7.5Hz, 1H), 7.47 (dd, J = 7.5, 1.2Hz, 1H), 7.32 (dd, J = 7.2, 1.2 Hz, 1H), 6.79 (d, J = 7.2 Hz, 1H), 4.26-4.19 (m, 1H), 4.03-3.96 (m, 1H), 3.88-3.78 br, 2H), 2.72-2.67 (m, 2H), 2.67-2.60 (m, 2H), 2.50-2.42 (m, 2H).
[3656] Example 72 (3)
[3657] 4- (N-methyl-N-methoxycarbamoyl) -1,1-dioxide benzo [b] thiophene
[3658]
[3659] TLC: Rf 0.22 (hexane: AcOEt = 1: 1);
[3660] _{NMR (CDCl 3): δ 7.78} (dt, J = 7.8, 1.0Hz, 1H), 7.72 (dd, J = 7.8, 1.0Hz, 1H), 7.57 (t, J = 7.8Hz, 1H), 7.41 (dd J = 7.0, 1.0 Hz, 1H), 6.76 (d, J = 7.0 Hz, 1H), 3.49 (s, 3H), 3.40 (s, 3H).
[3661] Example 72 (4)
[3662] 4- (4- (thiazol-2-ylsulfamoyl) phenyl) carbamoyl-l, l-dioxide benzo [b] thiophene
[3663]
[3664] TLC: Rf 0.20 (CHCl 3: MeOH = 9: 1);
[3665] _{NMR (CDCl 3 + DMSO-d} 6): δ 10.71 (s, 1H), 7.98 (d, J = 7.5Hz, 1H), 7.90-7.67 (m, 6H), 7.67 (t, J = 7.8Hz, 1H ), 6.97 (d, J = 7.5 Hz, 1H), 6.94 (d, J = 5 Hz, 1H), 6.52 (d, J = 5 Hz, 1H), 5.30 (broad peak, 1H).
[3666] Example 72 (5)
[3667] 4 - ((1R) -1-t-butoxycarbonyl-2-methylpropyl) carbamoyl-1,1-dioxide benzo [b] thiophene
[3668]
[3669] TLC: Rf 0.48 (hexane: AcOEt = 1: 1);
[3670] _{NMR (CDCl 3): δ 7.95} (dd, J = 7.2, 1.0Hz, 1H), 7.81 (d, J = 7.8Hz, 1H), 7.76 (dd, J = 7.8, 1.0Hz, 1H), 7.59 (t J = 8.4 Hz, 1H), 6.78 (d, J = 7.2 Hz, 1H), 6.55 (m, 1H), 1.51 (s, 9H), 1.02 (d, J = 6.9 Hz, 3H), 0.98 (d, J = 6.9 Hz, 3H).
[3671] Example 72 (6)
[3672] 6- (l-Benzylpiperidin-4-yl) carbamoyl-4-methoxy-l, l-dioxide benzo [b] thiophene
[3673]
[3674] TLC: Rf 0.44 (ethyl acetate: methanol = 4: 1);
[3675] _{NMR (CDCl 3): δ 7.66} (s, 1H), 7.54 (s, 1H), 7.45 (d, J = 7.0Hz, 1H), 7.40-7.20 (m, 5H), 6.73 (d, J = 7.0Hz 2H), 3.00-2.80 (m, 2H), 2.30-2.10 (m, 1H), 3.40 , 2H), 2.10-1.90 (m, 2H), 1.70-1.50 (m, 2H).
[3676] Example 72 (7)
[3677] 6- (2-diethylaminoethyl) carbamoyl-4-methoxy-l, l-dioxide benzo [b] thiophene
[3678]
[3679] TLC: Rf 0.33 (ethyl acetate: methanol: triethylamine = 14: 4: 1);
[3680] _{NMR (CDCl 3): δ 7.71} (s, 1H), 7.57 (s, 1H), 7.46 (d, J = 6.9Hz, 1H), 7.10-7.00 (m, 1H), 6.71 (d, J = 6.9Hz (S, 3H), 3.52 (q, J = 5.5 Hz, 2H), 2.53 (t, J = 5.5 Hz, 2H), 2.28 (s, 6H).
[3681] Example 72 (8)
[3682] 6- (Pyridin-3-ylmethyl) carbamoyl-4-methoxy-l, l-dioxide benzo [b] thiophene
[3683]
[3684] TLC: Rf 0.49 (ethyl acetate: methanol = 4: 1);
[3685] _{NMR (DMSO-d 6):} δ 9.36 (t, J = 6.0Hz, 1H), 8.58 (s, 1H), 8.48 (d, J = 4.5Hz, 1H), 7.88 (s, 1H), 7.81 (s J = 7.0 Hz, 1H), 7.75 (d, J = 7.8 Hz, 1H), 7.64 , 1H), 4.53 (d, J = 6.0 Hz, 2H), 3.99 (s, 3H).
[3686] Example 72 (9)
[3687] 5- (6-dimethylaminohexyl) oxycarbonyl-1,1-dioxide benzo [b] thiophene hydrochloride
[3688]
[3689] TLC: Rf 0.16 (CHCl 3: MeOH = 9: 1);
[3690] _{NMR (CDCl 3): δ 12.60-12.30} (br, 1H), 7.96 (d, J = 7.4Hz, 1H), 7.54-7.43 (m, 2H), 6.76 (d, J = 7.2Hz, 1H), 4.35 2H), 3.97 (s, 3H), 3.06-2.90 (m, 2H), 2.81 (s, 3H), 2.79 1.57-1.35 (m, 4H).
[3691] Example 72 (10)
[3692] 4- (4-t-butoxycarbonylpiperazin-1-yl) carbonyl-1,1-dioxo [b] thiophene
[3693]
[3694] TLC: Rf 0.65 (methylene chloride: methanol = 10: 1);
[3695] _{NMR (CDCl 3): δ 7.78} (dd, J = 7.2, 1.2Hz, 1H), 7.59 (t, J = 7.2Hz, 1H), 7.48 (dd, J = 7.2, 1.2Hz, 1H), 7.32 (d 2H), 3.65-3.45 (m, 2H), 3.45-3.24 (m, 4H), 1.47 (m, s, 9H).
[3696] Example 72 (11)
[3697] 4- (Piperazin-1-yl) carbonyl-1,1-dioxo [b] thiophene hydrochloride
[3698]
[3699] TLC: Rf 0.13 (methylene chloride: methanol = 10: 1);
[3700] _{NMR (DMSO-d 6):} δ 9.35 (bs, 2H), 7.96 (d, J = 6.9Hz, 1H), 7.80-7.73 (m, 2H), 7.60 (d, J = 7.2Hz, 1H), 7.51 (d, J = 7.2 Hz, 1H), 4.00-3.80 (m, 2H), 3.60-3.40 (m, 2H), 3.30-3.15 (m, 2H), 3.15-3.00 (m, 2H).
[3701] Example 72 (12)
[3702] 4-methoxyphenylmethyl) piperazin-1-yl) carbonyl-1,1-dioxide benzo [b] thiophene hydrochloride
[3703]
[3704] TLC: Rf 0.50 (methylene chloride: methanol = 10: 1);
[3705] _{NMR (DMSO-d 6):} δ 7.97 (t, J = 4.2Hz, 1H), 7.71 (d, J = 4.2Hz, 2H), 7.58-7.43 (m, 2H), 7.54 (d, J = 4.2Hz 2H), 7.01 (d, J = 8.4 Hz, 2H), 4.65-4.50 (m, 1H), 4.30-4.20 (m, 2H), 3.78 (s, 00 (m, 8H).
[3706] Example 72 (13)
[3707] Piperazin-1-yl) carbonyl-1,1-dioxo [b] thiophene hydrochloride
[3708]
[3709] TLC: Rf 0.33 (ethyl acetate);
[3710] _{NMR (DMSO-d 6):} δ 8.00-7.92 (m, 1H), 7.80-7.64 (m, 8H), 7.60-7.35 (m, 5H), 4.65-4.50 (m, 1H), 4.48-4.30 (m , 2H), 3.70-3.00 (m, 8H).
[3711] Example 72 (14)
[3712] 1-yl) carbonyl-1,1-dioxo [b] thiophene hydrochloride (4-methoxyphenyl)
[3713]
[3714] TLC: Rf 0.70 (ethyl acetate);
[3715] _{NMR (DMSO-d 6):} δ 8.42-7.30 (m, 1H), 8.13-7.77 (m, 4H), 7.76-7.40 (m, 7H), 4.93-4.76 (m, 2H), 4.66-4.53 (m , &Lt; / RTI &gt; 1H), 3.64-3.00 (m, 8H).
[3716] Example 72 (15)
[3717] Piperazin-1-yl) carbonyl-1,1-dioxo [b] thiophene hydrochloride
[3718]
[3719] TLC: Rf 0.40 (ethyl acetate);
[3720] _{NMR (DMSO-d 6):} δ 7.98 (t, J = 4.2Hz, 1H), 7.71 (d, J = 4.2Hz, 2H), 7.56 (d, J = 7.2Hz, 1H), 7.52 (d, J = 7.2 Hz, 1H), 7.47 (d, J = 7.8 Hz, 2H), 7.31 (d, J = 7.8 Hz, 2H), 4.66-4.45 2H), 1.19 (t, J = 7.5 Hz, 3H), 2.63 (q, J = 7.5 Hz, 2H).
[3721] Example 72 (16)
[3722] 1-yl) carbonyl-1,1-dioxide benzo [b] thiophene hydrochloride (hereinafter abbreviated as &quot;
[3723]
[3724] TLC: Rf 0.40 (ethyl acetate);
[3725] _{NMR (DMSO-d 6):} δ 8.72 (s, 1H), 8.20-7.93 (m, 5H), 7.80-7.64 (m, 4H), 7.60 (d, J = 7.2Hz, 1H), 7.55 (d, J = 7.2 Hz, 1H), 5.30-5.10 (m, 2H), 4.60-4.40 (m, 1H), 3.80-3.10 (m, 8H).
[3726] Example 72 (17)
[3727] Yl) carbonyl-1, 1-dioxo [b] thiophene dihydrochloride
[3728]
[3729] TLC: Rf 0.46 (methylene chloride: methanol = 10: 1);
[3730] _{NMR (DMSO-d 6):} δ 8.69 (d, J = 5.1Hz, 1H), 8.00-7.90 (m, 2H), 7.75-7.64 (m, 3H), 7.60-7.46 (m, 3H), 4.50 ( s, 2H), 4.09-3.90 (m, 2H), 3.67-3.59 (m, 2H), 3.48-3.35 (m, 2H), 3.33-3.20 (m, 2H).
[3731] Example 72 (18)
[3732] Yl) carbonyl-1, 1-dioxo [b] thiophene dihydrochloride
[3733]
[3734] TLC: Rf 0.46 (methylene chloride: methanol = 10: 1);
[3735] _{NMR (DMSO-d 6):} δ 8.90 (s, 1H), 8.80-8.73 (m, 1H), 8.36-8.30 (m, 1H), 7.98-7.92 (m, 1H), 7.80-7.66 (m, 3H ), 7.57 (d, J = 7.2 Hz, 1H), 7.52 (d, J = 7.2 Hz, 1H), 4.50-3.00 (m,
[3736] Example 72 (19)
[3737] 4- (4-benzoylpiperazin-1-yl) carbonyl-1, 1-dioxide benzo [b] thiophene
[3738]
[3739] TLC: Rf 0.52 (methylene chloride: methanol = 10: 1);
[3740] _{NMR (CDCl 3): δ 7.79} (d, J = 7.5Hz, 1H), 7.59 (t, J = 7.5Hz, 1H), 7.53-7.36 (m, 6H), 7.34 (d, J = 6.0Hz, 1H ), 6.81 (d, J = 7.5 Hz, 1H), 4.00-3.25 (m, 8H).
[3741] Example 72 (20)
[3742] Carbonyl) piperazin-1-yl) carbonyl-1,1-dioxide benzo [b] thiophene
[3743]
[3744] TLC: Rf 0.46 (methylene chloride: methanol = 10: 1);
[3745] _{NMR (CDCl 3): δ 7.80} (d, J = 6.9Hz, 1H), 7.61 (t, J = 7.8Hz, 1H), 7.51 (d, J = 7.8Hz, 2H), 7.35 (d, J = 6.9 (D, J = 3.6 Hz, 1H), 6.81 (d, J = 6.9 Hz, 1H), 6.52 06-3. 36 (m, 8H).
[3746] Example 72 (21)
[3747] 4- (4-Benzylcarbonylpiperazin-1-yl) carbonyl-1,1-dioxo [b] thiophene
[3748]
[3749] TLC: Rf 0.47 (methylene chloride: methanol = 10: 1);
[3750] _{NMR (CDCl 3): δ 7.77} (d, J = 7.5Hz, 1H), 7.57 (t, J = 7.5Hz, 1H), 7.48-7.14 (m, 6H), 7.28 (d, J = 7.2Hz, 1H ), 6.78 (d, J = 7.2 Hz, 1H), 3.86-3.00 (m, 10H).
[3751] Example 72 (22)
[3752] 4- (2- (pyrrolidin-1-yl) ethyl) carbamoyl-l, l-dioxide benzo [b] thiophene
[3753]
[3754] TLC: Rf 0.26 (ethyl acetate: acetic acid: water = 3: 1: 1);
[3755] _{NMR (CDCl 3): δ 8.00} (dd, J = 7.5Hz and 1Hz, 1H), 7.79 (dt , J = 7.5Hz and 1Hz,
[3756] (D, J = 7.5 Hz, 1H), 7.57 (t, J = 7.5 Hz, 1H), 6.72 (m, 2H), 2.73 (t, J = 6 Hz, 2H), 2.57 (m, 4H), 1.80 (m, 4H).
[3757] Example 72 (23)
[3758] 4- (3- (pyrrolidin-1-yl) propyl) carbamoyl-1,1-dioxide benzo [b] thiophene
[3759]
[3760] TLC: Rf 0.19 (ethyl acetate: acetic acid: water = 3: 1: 1);
[3761] _{NMR (CDCl 3): δ 9.30} (broad s, 1H), 8.17 (d, J = 7.5Hz, 1H), 7.78 (d, J = 7.5Hz, 1H), 7.64 (d, J = 7.5Hz, 1H) , 7.52 (t, J = 7.5 Hz, 1H), 6.76 (d, J = 7.5 Hz, 1H), 3.58 (m, 2H) , 2.00-1.70 (m, 6H).
[3762] Example 72 (24)
[3763] Yl) carbonyl-1, 1-dioxo [b] thiophene hydrochloride (2-methylphenyl)
[3764]
[3765] TLC: Rf 0.64 (ethyl acetate: hexane = 2: 1);
[3766] _{NMR (DMSO-d 6):} δ 7.97-7.90 (m, 1H), 7.74-7.65 (m, 2H), 7.57 (d, J = 7.2Hz, 1H), 7.51 (d, J = 7.2Hz, 1H) 2H), 3.20-3. 45 (m, 2H), 3.20-3.40 (m, m, 2 H), 2.27 (s, 3 H).
[3767] Example 72 (25)
[3768] 4- (4- (3-methylphenyl) piperazin-1-yl) carbonyl-1,1-dioxide benzo [b] thiophene hydrochloride
[3769]
[3770] TLC: Rf 0.48 (ethyl acetate: hexane = 2: 1);
[3771] _{NMR (DMSO-d 6):} δ 8.00-7.92 (m, 1H), 7.74-7.66 (m, 2H), 7.56 (d, J = 7.2Hz, 1H), 7.49 (d, J = 7.2Hz, 1H) , 7.14 (t, J = 7.8 Hz, 1H), 6.90-6.80 (m, 2H), 6.71 (d, J = 7.8 Hz, 1H), 3.90-3.80 , 2H), 3.36-3.24 (m, 2H), 3.18-3.08 (m, 2H), 2.56 (s, 3H).
[3772] Example 72 (26)
[3773] 1-yl) carbonyl-1,1-dioxo-benzo [b] thiophene hydrochloride
[3774]
[3775] TLC: Rf 0.59 (ethyl acetate: hexane = 2: 1);
[3776] _{NMR (DMSO-d 6):} δ 8.00-7.90 (m, 1H), 7.74-7.66 (m, 2H), 7.56 (d, J = 7.2Hz, 1H), 7.50 (d, J = 7.2Hz, 1H) , 7.20-6.96 (m, 4H), 3.90-3.80 (m, 2H), 3.46-3.36 (m, 2H), 3.18-3.06 (m, 2H), 3.02-2.90 (m, 2H).
[3777] Example 72 (27)
[3778] (4- (4-fluorophenyl) piperazin-1-yl) carbonyl-1,1-dioxide benzo [b] thiophene hydrochloride
[3779]
[3780] TLC: Rf 0.40 (ethyl acetate: hexane = 2: 1);
[3781] _{NMR (DMSO-d 6):} δ 8.00-7.90 (m, 1H), 7.74-7.65 (m, 2H), 7.54 (d, J = 6.9Hz, 1H), 7.49 (d, J = 6.9Hz, 1H) , 7.14-6.97 (m, 4H), 3.89-3.78 (m, 2H), 3.45-3.34 (m, 2H), 3.30-3.19 (m, 2H), 3.13-3.00 (m, 2H).
[3782] Example 72 (28)
[3783] 4-methoxyphenyl) piperazin-1-yl) carbonyl-1,1-dioxide benzo [b] thiophene hydrochloride
[3784]
[3785] TLC: Rf 0.22 (AcOEt: hexane = 2: 1);
[3786] _{NMR (DMSO-d 6):} δ 8.00-7.92 (m, 1H), 7.77-7.66 (m, 2H), 7.58 (d, J = 6.9Hz, 1H), 7.50 (d, J = 6.9Hz, 1H) , 7.13-7.08 (m, 2H), 6.96-6.86 (m, 2H), 4.10-3.70 (m, 2H), 3.72 (s, 3H), 3.54-3. 38-3.22 (m, 2H), 3.20-3.06 (m, 2H).
[3787] Example 72 (29)
[3788] Piperazin-1-yl) carbonyl-1,1-dioxide benzo [b] thiophene hydrochloride
[3789]
[3790] TLC: Rf 0.47 (AcOEt: hexane = 2: 1);
[3791] _{NMR (DMSO-d 6):} δ 7.98-7.93 (m, 1H), 7.74-7.67 (m, 2H), 7.56 (d, J = 6.9Hz, 1H), 7.49 (d, J = 6.9Hz, 1H) , 7.48-7.40 (m, 1H), 7.27-7.16 (m, 2H), 7.14-7.07 (m, 1H), 3.88-3.67 (m, 2H), 3.46-3.34 (m, 4H), 3.27-3.18 m, 2H).
[3792] Example 72 (30)
[3793] 4 - ((3R) -1-benzylpyrrolidin-3-yl) carbamoyl- 1, 1-dioxide benzo [b] thiophene
[3794]
[3795] TLC: Rf 0.45 (CHCl 3: MeOH = 9: 1);
[3796] _{NMR (CDCl 3): δ 7.92} (dd, J = 1.0Hz and 7.0Hz, 1H), 7.77 (d , J = 7.5Hz, 1H), 7.68 (dd, J = 1.0Hz and 7.5Hz, 1H), 7.54 (d, J = 7.0 Hz, 1H), 6.70 (m, 1H), 4.65 (m, 1H), 3.66 2H), 3.05-2.95 (m, 1H), 2.78 (dd, J = 1.0 Hz and 10 Hz, 1H), 2.60 (dd, J = 6.0 Hz and 10 Hz, -1.70 (m, 1 H).
[3797] Example 72 (31)
[3798] 4 - ((3S) -1-benzylpyrrolidin-3-yl) carbamoyl-1,1-dioxide benzo [b] thiophene
[3799]
[3800] TLC: Rf 0.45 (CHCl 3: MeOH = 9: 1);
[3801] _{NMR (CDCl 3): δ 7.92} (dd, J = 1.0Hz and 7.0Hz, 1H), 7.77 (d , J = 7.5Hz, 1H), 7.68 (dd, J = 1.0Hz and 7.5Hz, 1H), 7.54 (d, J = 7.0 Hz, 1H), 6.70 (m, 1H), 4.65 (m, 1H), 3.66 2H), 3.05-2.95 (m, 1H), 2.78 (dd, J = 1.0 Hz and 10 Hz, 1H), 2.60 (dd, J = 6.0 Hz and 10 Hz, -1.70 (m, 1 H).
[3802] Examples 73 to 73 (29)
[3803] The operation was carried out in the same manner as in Example 18 using the corresponding alcohol derivative and the corresponding halide corresponding to 4-nitrobenzyl bromide in the compound prepared in Example 9 (12), or by using 4-hydroxy-1,1 -Dioxane benzo [b] thiophene and the corresponding alcohol derivative of 1- (3-hydroxypropyl) pyrrole in the same manner as in the method of Example 29, the following compounds of the present invention were obtained .
[3804] In addition, the compounds of Examples 73 (26) to 73 (29) were prepared by the method shown in Example 18 using sodium hydroxide aqueous solution instead of potassium carbonate.
[3805] Example 73
[3806] 5-acetylmethyloxy-1,1-dioxide benzo [b] thiophene
[3807]
[3808] TLC: Rf 0.25 (ethyl acetate: hexane: methylene chloride = 1: 1: 1);
[3809] _{NMR (CDCl 3): δ 7.65} (d, J = 8.2Hz, 1H), 7.15 (d, J = 6.8Hz, 1H), 6.92 (dd, J = 8.2Hz, 2.2Hz, 1H), 6.87 (d, J = 2.2 Hz, 1H), 6.75 (d, J = 6.8 Hz, 1H), 4.64 (s, 2H), 2.30 (s, 3H).
[3810] Example 73 (1)
[3811] 5-Cyanomethyloxy-1,1-dioxide benzo [b] thiophene
[3812]
[3813] TLC: Rf 0.36 (hexane: AcOEt = 1: 1);
[3814] _{NMR (CDCl 3): δ 7.72} (d, J = 8.4Hz, 1H), 7.18 (d, J = 7.2Hz, 1H), 7.07 (dd, J = 8.4, 2.4Hz, 1H), 6.98 (d, J = 2.4 Hz, 1 H), 6.79 (d, J = 7.2 Hz, 1 H), 4.86 (s, 2H).
[3815] Example 73 (2)
[3816] 5-t-butoxycarbonylmethyloxy-1,1-dioxide benzo [b] thiophene
[3817]
[3818] TLC: Rf 0.54 (hexane: AcOEt = 1: 1);
[3819] _{NMR (CDCl 3): δ 7.63} (d, J = 8.4Hz, 1H), 7.13 (d, J = 6.9Hz, 1H), 6.91 (dd, J = 8.4, 2.4Hz, 1H), 6.88 (d, J = 2.4 Hz, 1H), 6.73 (d, J = 6.9 Hz, 1H), 4.58 (s, 2H), 1.49 (s, 9H).
[3820] Example 73 (3)
[3821] 5- (3- (ethoxycarbonyl) propyl) oxy-1, 1-dioxide benzo [b] thiophene
[3822]
[3823] TLC: Rf 0.50 (hexane: AcOEt = 1: 1);
[3824] _{NMR (CDCl 3): δ 7.61} (d, J = 8.7Hz, 1H), 7.12 (d, J = 6.9Hz, 1H), 6.94 (dd, J = 8.7, 2.0Hz, 1H), 6.84 (d, J = 2.0 Hz, 1H), 6.71 (d, J = 6.9 Hz, 1H), 4.15 (q, J = 7.2 Hz, 2H), 4.08 Hz, 1H), 2.13 (quintet, J = 6.6 Hz, 1H), 1.26 (t, J = 7.2 Hz, 3H).
[3825] Example 73 (4)
[3826] 5- (4- (ethoxycarbonyl) butyl) oxy-1,1-dioxide benzo [b] thiophene
[3827]
[3828] TLC: Rf 0.48 (hexane: AcOEt = 1: 1);
[3829] _{NMR (CDCl 3): δ 7.61} (dd, J = 8.4, 0.9Hz, 1H), 7.12 (dd, J = 6.9, 0.9Hz, 1H), 6.93 (dd, J = 8.4, 2.4Hz, 1H), 6.84 (d, J = 2.4 Hz, 1H), 6.71 (d, J = 6.9 Hz, 1H), 4.13 (q, J = 7.0 Hz, 2H), 4.03 , J = 7.0 Hz, 2H), 1.88-1.80 (m, 4H), 1.26 (t, J = 7.0 Hz, 3H).
[3830] Example 73 (5)
[3831] 4- (Pyridin-3-ylmethyl) oxy-1, 1-dioxide benzo [b] thiophene
[3832]
[3833] TLC: Rf 0.42 (ethyl acetate: methanol = 9: 1);
[3834] _{NMR (CDCl 3): δ 5.19} (s, 2H), 6.63 (d, J = 7.0Hz, 1H), 7.13 (d, J = 8.0Hz, 1H), 7.33 (d, J = 8.0Hz, 1H), J = 8.0 Hz, 1H), 7.75 (dt, J = 8.0 Hz, 1H), 7.37 (dd, J = 8.0 Hz, 5.0 Hz, 1H) , 2.0Hz, 1H), 8.64 (dd, J = 5.0Hz, 2.0Hz, 1H), 8.70 (d, J = 2.0Hz, 1H).
[3835] Example 73 (6)
[3836] 4- (Pyridin-4-ylmethyl) oxy-l, l-dioxide benzo [b] thiophene
[3837]
[3838] TLC: Rf 0.16 (methylene chloride: ethyl acetate = 1: 1);
[3839] _{NMR (CDCl 3): δ 8.66} (d, J = 6.0Hz, 2H), 7.51 (dd, J = 7.0, 1.0Hz, 1H), 7.47 (t, J = 8.0Hz, 1H), 7.36-7.31 (m , 3H), 7.03 (d, J = 8.0 Hz, 1H), 6.67 (d, J = 7.0 Hz, 1H), 5.21 (s, 2H).
[3840] Example 73 (7)
[3841] 3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene (4-trifluoromethylphenylmethyl)
[3842]
[3843] TLC: Rf 0.67 (hexane: AcOEt = 1: 2);
[3844] _{NMR (CDCl 3): δ 7.70} (d, J = 7.5Hz, 2H), 7.60-7.30 (m, 5H), 7.10 (d, J = 10Hz, 1H), 6.65 (d, J = 7.5Hz, 1H) , 5.25 (s, 2H).
[3845] Example 73 (8)
[3846] 4- (3,5-dimethylisoxazol-4-ylmethyl) oxy-1, 1-dioxide benzo [b] thiophene
[3847]
[3848] TLC: Rf 0.53 (hexane: ethyl acetate = 1: 2);
[3849] _{NMR (CDCl 3): δ 7.60-7.40} (m, 1H), 7.40-7.30 (m, 2H), 7.10 (d, J = 7.5Hz, 1H), 6.60 (d, J = 7.5Hz, 1H), 4.90 (s, 2H), 2.40 (s, 3H), 2.30 (s, 3H).
[3850] Example 73 (9)
[3851] 4- (4-methoxycarbonylphenylmethyl) oxy-1, 1-dioxide benzo [b] thiophene
[3852]
[3853] TLC: Rf 0.58 (hexane: AcOEt = 1: 2);
[3854] _{NMR (CDCl 3): δ 8.10} (d, J = 7.5Hz, 2H), 7.55-7.30 (m, 5H), 7.10 (d, J = 10Hz, 1H), 6.65 (d, J = 7.5Hz, 1H) , 5.25 (s, 2 H), 3.95 (s, 3 H).
[3855] Example 73 (10)
[3856] 4- (benzotriazol-1-ylmethyl) oxy-1, 1-dioxide benzo [b] thiophene
[3857]
[3858] TLC: Rf 0.62 (hexane: AcOEt = 1: 2);
[3859] _{NMR (CDCl 3): δ 8.20-8.10} (m, 1H), 7.70-7.30 (m, 7H), 6.65 (s, 2H), 6.60 (d, J = 7.5Hz, 1H).
[3860] Example 73 (11)
[3861] 4- (2,6-dimethylphenyl) carbamoylmethyloxy-1,1-dioxide benzo [b] thiophene
[3862]
[3863] TLC: Rf 0.50 (hexane: AcOEt = 1: 2);
[3864] _{NMR (CDCl 3): δ 7.65-7.40} (m, 4H), 7.20-7.00 (m, 4H), 6.75 (d, J = 7.5Hz, 1H), 4.80 (s, 2H), 2.20 (s, 6H) .
[3865] Example 73 (12)
[3866] 4-trimethylsilylmethyloxy-1,1-dioxide benzo [b] thiophene
[3867]
[3868] TLC: Rf 0.60 (hexane: AcOEt = 1: 1);
[3869] _{NMR (CDCl 3): δ 7.50-7.35} (m, 2H), 7.30-7.10 (m, 2H), 6.60 (d, J = 7.5Hz, 1H), 3.70 (s, 2H), 0.20 (s, 9H) .
[3870] Example 73 (13)
[3871] 4- (Pyridin-2-ylmethyl) oxy-1, 1-dioxo [b] thiophene
[3872]
[3873] TLC: Rf 0.31 (hexane: AcOEt = 1: 2);
[3874] _{NMR (CDCl 3): δ 8.70-8.55} (m, 1H), 7.85-7.70 (m, 1H), 7.60-7.20 (m, 5H), 7.10 (d, J = 7.5Hz, 1H), 6.65 (d, J = 7.5 Hz, 1H), 5.35 (s, 2H).
[3875] Example 73 (14)
[3876] 4- (2- (pyridin-3-ylcarbonyl) aminoethyl) oxy-1, 1-dioxide benzo [b] thiophene
[3877]
[3878] TLC: Rf 0.33 (ethyl acetate: methanol = 9: 1);
[3879] _{NMR (CDCl 3): δ 8.98} (dd, J = 1.8, 0.9Hz, 1H), 8.72 (dd, J = 4.5, 1.8Hz, 1H), 8.12 (dt, J = 8.0, 1.8Hz, 1H), 7.49 7.08 (d, J = 8.0 Hz, 1H), 6.83 (br, 1H), 6.58 (d, J = 7.0 Hz, 1H) , 4.30 (t, J = 5.4 Hz, 2H), 3.93 (q, J = 5.4 Hz, 2H).
[3880] Example 73 (15)
[3881] 4- (3- (pyridin-3-yl) propyl) oxy-1,1-dioxide benzo [b] thiophene
[3882]
[3883] TLC: Rf 0.32 (ethyl acetate: methanol = 10: 1);
[3884] _{NMR (CDCl 3 + CD 3 OD} ): δ 8.52-8.25 (m, 2H), 7.80-7.18 (m, 5H), 7.07 (d, J = 8Hz, 1H), 6.68 (d, J = 7Hz, 1H) , 4.14 (t, J = 7 Hz, 2H), 2.87 (t, J = 7 Hz, 2H), 2.35-2.10 (m, 2H).
[3885] Example 73 (16)
[3886] 4- (2- (pyridin-2-yl) ethyl) oxy-1,1-dioxide benzo [b] thiophene
[3887]
[3888] TLC: Rf 0.39 (ethyl acetate: methanol = 10: 1);
[3889] _{NMR (CDCl 3): δ 8.57} (d, J = 5Hz, 1H), 7.64 (dt, J = 2, 7Hz, 1H), 7.45 (t, J = 8Hz, 1H), 7.35-6.98 (m, 5H) , 6.56 (d, J = 7 Hz, 1H), 4.50 (t, J = 7 Hz, 2H), 3.29 (t, J = 7 Hz, 2H).
[3890] Example 73 (17)
[3891] 4- (1-t-butoxycarbonylpiperidin-4-yl) oxy-1,1-dioxide benzo [b] thiophene
[3892]
[3893] TLC: Rf 0.63 (ethyl acetate: hexane = 1: 1);
[3894] _{NMR (CDCl 3): δ 7.55-7.38} (m, 2H), 7.30 (d, J = 8Hz, 1H), 7.07 (d, J = 8Hz, 1H), 6.23 (d, J = 7Hz, 1H), 4.70 2H), 1.47 (m, 2H), 1.47 (m, 2H), 1.47 (m, .
[3895] Example 73 (18)
[3896] Methyl-1-tritylimidazol-4-ylmethyl) oxy-1,1-dioxide benzo [b] thiophene
[3897]
[3898] TLC: Rf 0.11 (hexane: AcOEt = 1: 1);
[3899] _{NMR (CDCl 3): δ 7.55-7.23} (m, 14H), 7.23-7.00 (m, 6H), 6.56 (d, J = 7Hz, 1H), 5.13 (s, 2H), 1.45 (s, 3H).
[3900] Example 73 (19)
[3901] 4- (1,2,4-oxadiazol-3-ylmethyl) oxy-1, 1-dioxide benzo [b] thiophene
[3902]
[3903] TLC: Rf 0.45 (hexane: AcOEt = 1: 2);
[3904] _{NMR (DMSO-d 6):} δ 9.70 (s, 1H), 7.62 (t, J = 8.0Hz, 1H), 7.57 (d, J = 6.9Hz, 1H), 7.50 (d, J = 8.0Hz, 1H ), 7.46 (d, J = 8.0 Hz, 1H), 7.31 (d, J = 6.9 Hz, 1H), 5.58 (s, 2H).
[3905] Example 73 (20)
[3906] 6- (Pyridin-3-ylmethyl) oxy-1, 1-dioxo [b] thiophene
[3907]
[3908] TLC: Rf 0.40 (ethyl acetate);
[3909] _{NMR (CDCl 3): δ 8.69} (d, J = 1.7Hz, 1H), 8.62 (dd, J = 5.0, 1.7Hz, 1H), 7.77 (d, J = 7.8Hz, 1H), 7.39-7.27 (m J = 7.0 Hz, 1H), 7.04 (dd, J = 8.2, 2.2 Hz, 1H), 6.58 (d, J = 7.0 Hz, 1H), 5.14 (s, 2H).
[3910] Example 73 (21)
[3911] 6- (3-nitrophenylmethyl) oxy-1, 1-dioxide benzo [b] thiophene
[3912]
[3913] MS (APCI, Pos.): M / z 318 (M + H) &lt; ⁺ & gt ^; .
[3914] Example 73 (22)
[3915] 6- (3- (t-butoxycarbonylamino) propyl) oxy-1,1-dioxide benzo [b] thiophene
[3916]
[3917] TLC: Rf 0.14 (hexane: AcOEt = 2: 1);
[3918] _{NMR (CDCl 3): δ 7.27-7.23} (m, 2H), 7.16 (d, J = 6.9Hz, 1H), 7.01 (dd, J = 8.3, 2.3Hz, 1H), 6.60 (d, J = 6.9Hz (T, J = 6.6 Hz, 2H), 3.32 (q, J = 6.6 Hz, 2H), 2.01 (quintet, J = 6.6 Hz, 2H), 1.44 s, 9H).
[3919] Example 73 (23)
[3920] 7-t-Butoxycarbonylmethyloxy-1,1-dioxide benzo [b] thiophene
[3921]
[3922] TLC: Rf 0.41 (hexane: AcOEt = 1: 1);
[3923] _{NMR (CDCl 3): δ 7.45} (dd, J = 8.5, 7.5Hz, 1H), 7.12 (d, J = 6.9Hz, 1H), 6.94 (d, J = 7.5Hz, 1H), 6.86 (d, J = 8.5 Hz, 1H), 6.66 (d, J = 6.9 Hz, 1H), 4.72 (s, 2H), 1.46 (s, 9H).
[3924] Example 73 (24)
[3925] 6- (Pyridin-3-yloxy) methyl-4-methoxy-1,1-dioxo [
[3926]
[3927] TLC: Rf 0.36 (ethyl acetate);
[3928] _{NMR (CD 3 OD): δ} 8.35 (d, J = 3.0Hz, 1H), 8.17 (d, J = 4.0Hz, 1H), 7.60-7.50 (m, 1H), 7.53 (d, J = 7.2Hz, 1H), 7.45-7.35 (m, 3H), 6.87 (d, J = 7.2 Hz, 1H), 5.27 (s, 2H), 3.98 (s, 3H).
[3929] Example 73 (25)
[3930] 4,7-bis (3-hydroxypropyl) -1,1-dioxide benzo [b] thiophene
[3931]
[3932] TLC: Rf 0.44 (ethyl acetate: methanol = 9: 1);
[3933] _{NMR (CDCl 3): δ 7.34} (d, J = 7.0Hz, 1H), 7.04 (d, J = 9.2Hz, 1H), 6.97 (d, J = 9.2Hz, 1H), 6.54 (d, J = 7.0 J = 5.8 Hz, 2H), 3.83 (t, J = 5.8 Hz, 2H), 3.83 (t, J = 5.8 Hz, 2H) 2H), 2.00-2. 08 (m, 4H).
[3934] Example 73 (26)
[3935] 5-carboxy-4-ethoxy-l, l-dioxide benzo [b] thiophene
[3936]
[3937] TLC: Rf 0.38 (CHCl 3: MeOH = 10: 1);
[3938] (CD ₃ OD): 隆 8.00 (d, J = 7 Hz, 1H), 7.61 (dd, J = 1, 7 Hz, 1H), 7.52 = 7 Hz, 1H), 4.16 (q, J = 7 Hz, 2H), 1.42 (t, J = 7 Hz, 3H).
[3939] Example 73 (27)
[3940] 5-carboxy-4-butoxy-1,1-dioxide benzo [b] thiophene
[3941]
[3942] TLC: Rf 0.48 (CHCl 3: MeOH = 10: 1);
[3943] (CD ₃ OD): 隆 7.98 (d, J = 7 Hz, 1H), 7.58 (dd, J = 1, 7 Hz, 1H), 7.51 = 7 Hz, 1H), 4.01 (t, J = 7 Hz, 2H), 1.95-1.66 (m, 2H), 1.66-1.36 (m, 2H), 0.99 (t, J = 7 Hz, 3H).
[3944] Example 73 (28)
[3945] 5-carboxy-4-hexyloxy-l, l-dioxo [b] thiophene
[3946]
[3947] TLC: Rf 0.50 (CHCl 3: MeOH = 10: 1);
[3948] (CD ₃ OD): 隆 7.98 (d, J = 7 Hz, 1H), 7.58 (dd, J = 1, 7 Hz, 1H), 7.51 = 7 Hz, 1H), 4.10 (t, J = 7 Hz, 2H), 1.95-1.65 (m, 2H), 1.65-1.05 (m, 6H), 0.92 (t, J = 7 Hz, 3H).
[3949] Example 73 (29)
[3950] 5-carboxy-4-octyloxy-l, l-dioxo [b] thiophene
[3951]
[3952] TLC: Rf 0.50 (CHCl 3: MeOH = 10: 1);
[3953] (CD ₃ OD): 隆 7.98 (d, J = 7 Hz, 1H), 7.57 (dd, J = 1, 7 Hz, 1H), 7.51 = 7 Hz, 1H), 4.10 (t, J = 7 Hz, 2H), 1.95-1.65 (m, 2H), 1.65-1.05 (m, 10H), 0.90 (t, J = 7 Hz, 3H).
[3954] Examples 74 to 74 (5)
[3955] 4-carboxy-1, 1-dioxide benzo [b] thiophene The title compound was obtained in the same manner as in Example 32 using the corresponding carboxylic acid derivative and bromoethane- The inventive compound was obtained.
[3956] However, in the preparation of the compound of Example 74, 1 mole equivalent of bromoethane was used.
[3957] Example 74
[3958] 5-ethoxycarbonyl-4-hydroxy-1,1-dioxide benzo [b] thiophene
[3959]
[3960] TLC: Rf 0.32 (hexane: AcOEt = 2: 1);
[3961] _{NMR (CDCl 3): δ 11.37} (s, 1H), 8.07 (d, J = 8.0Hz, 1H), 7.52 (dd, J = 7.0, 0.8Hz, 1H), 7.24 (dd, J = 8.0, 0.8Hz J = 7.0Hz, 1H), 6.66 (d, J = 7.0Hz, 1H), 4.47 (q, J = 7.0Hz, 2H), 1.45 (t,
[3962] Example 74 (1)
[3963] 5-ethoxycarbonyl-4-methoxy-1,1-dioxide benzo [b] thiophene
[3964]
[3965] TLC: Rf 0.31 (hexane: AcOEt = 2: 1);
[3966] _{NMR (CDCl 3): δ 7.98} (d, J = 7.4Hz, 1H), 7.49 (t, J = 7.4Hz, 2H), 6.75 (d, J = 7.4Hz, 1H), 4.43 (q, J = 7.0 Hz, 2H), 3.97 (s, 3H), 1.43 (t, J = 7.0 Hz, 3H).
[3967] Example 74 (2)
[3968] 5-Isopropyloxycarbonyl-4-methoxy-l, l-dioxide &lt; / RTI &gt;
[3969]
[3970] TLC: Rf 0.36 (hexane: AcOEt = 2: 1);
[3971] _{NMR (CDCl 3): δ 7.94} (d, J = 7.8Hz, 1H), 7.52-7.42 (m, 2H), 6.74 (d, J = 7.2Hz, 1H), 5.38-5.19 (m, 1H), 3.96 (s, 3H), 1.40 (d, J = 6.2 Hz, 6H).
[3972] Example 74 (3)
[3973] 5- (2-methylpropyl) oxycarbonyl-4-methoxy-1,1-dioxide benzo [b] thiophene
[3974]
[3975] TLC: Rf 0.42 (hexane: AcOEt = 2: 1);
[3976] _{NMR (CDCl 3): δ 7.97} (d, J = 7.8Hz, 1H), 7.53-7.43 (m, 2H), 6.75 (d, J = 7.2Hz, 1H), 4.15 (d, J = 6.8Hz, 2H ), 3.97 (s, 3H), 2.20-1.98 (m, 1H), 1.03 (d, J = 6.6Hz, 6H).
[3977] Example 74 (4)
[3978] Methoxycarbonyl-4-methoxy-l, l-dioxide &lt; / RTI &gt; benzo [b] thiophene
[3979]
[3980] TLC: Rf 0.41 (hexane: AcOEt = 1: 1);
[3981] _{NMR (CDCl 3): δ 7.95} (t, J = 1.0Hz, 1H), 7.75 (d, J = 1.0Hz, 1H), 7.46 (dd, J = 7.0, 1.0Hz, 1H), 6.74 (d, J = 7.0 Hz, IH), 3.98 (s, 3H), 3.96 (s, 3H).
[3982] Example 74 (5)
[3983] 6-Methoxymethoxycarbonyl-4-methoxy-1,1-dioxo [b] thiophene
[3984]
[3985] TLC: Rf 0.38 (hexane: AcOEt = 1: 1);
[3986] _{NMR (CDCl 3): δ 7.99} (s, 1H), 7.79 (s, 1H), 7.47 (d, J = 7.0Hz, 1H), 6.76 (d, J = 7.0Hz, 1H), 5.52 (s, 2H ), 4.00 (s, 3H), 3.58 (s, 3H).
[3987] Examples 75 to 75 (2)
[3988] The title compound was obtained in the same manner as in Example 31 using 4-bromomethyl-1,1-dioxide benzo [b] thiophene and an amine derivative corresponding to 2,4-dimethoxybenzylamine hydrochloride, To obtain a compound of the present invention.
[3989] However, in the production of the compound of Example 75 and Example 75 (2), 4-bromomethyl-1,1-dioxide benzo [b] thiophene was used in an amount of 2 molar equivalents or more based on the amine derivative .
[3990] Example 75
[3991] Yl) methyl) -1,1-dioxo [b] thiophene [b] thiophene A solution of 4- (N- (pyridin-
[3992]
[3993] TLC: Rf 0.48 (methanol: methylene chloride = 1: 10);
[3994] NMR (CDCl ₃ ): 8.59 (d, J = 4.6 Hz, 1H), 7.72-7.55 (m, 3H), 7.55-7.38 (m, 4H), 7.35-7.16 J = 7.8 Hz, 1H), 6.68 (d, J = 7.0 Hz, 2H), 3.76 (s, 4H), 3.73 (s, 2H).
[3995] Example 75 (1)
[3996] 4- (Pyridin-2-ylmethyl) aminomethyl-l, l-dioxide benzo [b] thiophene
[3997]
[3998] TLC: Rf 0.31 (methylene chloride: methanol = 10: 1);
[3999] _{NMR (CD 3 OD + CDCl 3} ): δ 8.75-8.52 (m, 1H), 7.96-7.72 (m, 4H), 7.64 (t, J = 8Hz, 1H), 7.55-7.25 (m, 2H), 6.93 (d, J = 7 Hz, 1 H), 4.43 (s, 2H), 4.38 (s, 2H).
[4000] Example 75 (2)
[4001] B) thiophen-4-ylmethyl) amino) methyl-1,1-dioxide benzo [b] thiophene Offen
[4002]
[4003] TLC: Rf 0.57 (ethyl acetate: benzene = 1: 1);
[4004] _{NMR (CDCl 3): δ 7.65-7.55} (m, 2H), 7.50-7.38 (m, 4H), 7.07-6.99 (m, 1H), 6.87 (d, J = 7.0Hz, 2H), 6.57 (d, J = 7.0 Hz, 2H), 6.48-6.40 (m, 2H), 3.81 (s, 3H), 3.63 (s, 3H), 3.60 (s, 4H), 3.45 (s, 2H).
[4005] Examples 76 to 76 (1)
[4006] 1,1-dioxide benzo [b] thiophene and thiophenol were used in the same manner as in Example 1 to give the following compounds of the present invention.
[4007] Example 76
[4008] 4,7-dimethoxy-3-phenylthio-2,3-dihydro-1, 1-dioxide benzo [b] thiophene
[4009]
[4010] TLC: Rf 0.27 (hexane: methylene chloride = 1: 10);
[4011] _{NMR (CDCl 3): δ 7.52-7.47} (m, 2H), 7.35-7.32 (m, 3H), 7.02 (d, J = 8.9Hz, 1H), 6.91 (d, J = 8.9Hz, 1H), 5.00 (dd, J = 7.0, 1.6 Hz, 1H), 3.92 (s, 3H), 3.85 Hz, 1H).
[4012] Example 76 (1)
[4013] 6-Bromo-3-phenylthio-2,3-dihydro-l, l-dioxo [
[4014]
[4015] TLC: Rf 0.45 (hexane: AcOEt = 2: 1);
[4016] _{NMR (CDCl 3): δ 7.83} (d, J = 1.8Hz, 1H), 7.75 (dd, J = 8.3, 1.8Hz, 1H), 7.58 (d, J = 8.3Hz, 1H), 7.43-7.40 (m J = 13.8, 6.9 Hz, 2H), 7.37-7.34 (m, 3H), 4.88 (t, J = 6.9 Hz, 1H), 3.80 (dd, J = 1H).
[4017] Example 77
[4018] 5-acetyloxy-4-nitro-1, 1-dioxo [b] thiophene
[4019]
[4020] The procedure of Example 12 was repeated except that 5-hydroxy-4-nitro-1,1-dioxide benzo [b] thiophene was used instead of the compound prepared in Example 11, Compound.
[4021] TLC: Rf 0.49 (hexane: AcOEt = 1: 1);
[4022] _{NMR (DMSO-d 6):} δ 8.32 (dd, J = 8.0, 1.0Hz, 1H), 7.78 (d, J = 7.0Hz, 1H), 7.76 (d, J = 8.0Hz, 1H), 7.69 (dd , J = 7.0, 1.0 Hz, 1 H), 2.35 (s, 3H).
[4023] Examples 78 to 78 (1)
[4024] The procedure of Example 7 was repeated using the compound prepared in Example 35 (39) and Example 35 (47) instead of the compound prepared in Example 6 (8) to obtain the compound &Lt; / RTI &gt;
[4025] Example 78
[4026] 4-Piperidin-3-ylmethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene hydrochloride
[4027]
[4028] TLC: Rf 0.41 and 0.50 (ethyl acetate: acetic acid: water = 3: 1: 1);
[4029] _{NMR (CD 3 OD): δ} 7.85-7.42 (m, 6H), 7.35-7.18 (m 2H), 5.68-5.50 (m, 1H), 4.15-3.90 (m, 3H), 3.90-3.50 (m, 2H ), 3.50-3.30 (m, 1H), 3.20-2.90 (m, 2H), 2.45-2.15 (m, 1H), 2.15-1.40 (m, 4H).
[4030] Example 78 (1)
[4031] Nitro-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene hydrochloride
[4032]
[4033] TLC: Rf 0.17 (ethyl acetate: methanol = 2: 1);
[4034] _{NMR (DMSO-d 6):} δ 8.25 (br, 3H), 8.16 (d, J = 8.7Hz, 1H), 7.86-7.65 (m, 6H), 5.99 (d, J = 7.2Hz, 1H), 4.63 -4.50 (m, 2H), 4.15-4.00 (m, 2H), 3.30-3.26 (m, 2H).
[4035] Example 79
[4036] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene (2-hydroxy-
[4037]
[4038] The compound (258 mg) prepared in Example 35 (42) was dissolved in ethanol, and a 47% aqueous hydrogen bromide solution (1.0 ml) was added and the mixture was heated under reflux for 1 hour. The reaction mixture was concentrated. The residue was dissolved in ethyl acetate, washed successively with saturated aqueous sodium hydrogen carbonate solution and saturated brine, dried over anhydrous sodium sulfate, and concentrated. The residue was recrystallized from ethyl acetate to obtain the compound (174 mg) of the present invention having the following physical data.
[4039] TLC: Rf 0.22 (ethyl acetate);
[4040] _{NMR (CDCl 3): δ 7.85-7.72} (m, 2H), 7.66-7.34 (m, 4H), 7.25 (d, J = 8Hz, 1H), 6.99 (d, J = 8Hz, 1H), 5.34 (d 1H), 4.19 (d, J = 15 Hz, 1H), 4.25-3.95 (m, 3H), 3.95-3.55 (m, 7H), 2.50 (brs, 1H).
[4041] Example 80
[4042] 4- (4,5-Dihydrooxazol-2-yl) -1,1-dioxo [b] thiophene
[4043]
[4044] The compound (369 mg) prepared in Example 72 (1) was dissolved in diisopropylethylamine (0.55 ml) and methylene chloride (40 ml), and the mixture was cooled to -78 ° C, trifluoromethanesulfonic anhydride (0.30 ml), and the mixture was stirred at -78 째 C for 2 hours, and the temperature was raised to 0 째 C. The reaction mixture was stirred at 0 占 폚 for 2.5 hours, then trifluoromethanesulfonic anhydride (0.15 ml) was added and stirred for 1 hour. The reaction mixture was stirred at room temperature for 1 hour. Ethyl acetate and 1N hydrochloric acid were added to the reaction mixture, and the mixture was extracted with ethyl acetate. The extract was washed sequentially with 1N aqueous sodium hydroxide solution and saturated brine, dried over anhydrous sodium sulfate and concentrated. The residue was purified by silica gel column chromatography (ethyl acetate: hexane = 1: 1) to obtain the present compound (97 mg) having the following physical data.
[4045] TLC: Rf 0.53 (ethyl acetate);
[4046] _{NMR (CDCl 3): δ 8.42} (d, J = 7.0Hz, 1H), 8.10 (d, J = 7.8Hz, 1H), 7.80 (d, J = 7.8Hz, 1H), 7.57 (t, J = 7.8 Hz), 6.77 (d, J = 7.0 Hz, 1H), 4.46 (t, J = 9.4 Hz, 2H), 4.13 (t, J = 9.4 Hz, 2H).
[4047] Example 80 (1)
[4048] 5- (4,5-dihydrooxazol-2-yl) -1,1-dioxo [b] thiophene
[4049]
[4050] The compound of the present invention having the following physical data was obtained by following the procedure of Example 80 while using the compound prepared in Example 28 (25) instead of the compound prepared in Example 72 (1).
[4051] TLC: Rf 0.39 (ethyl acetate);
[4052] _{NMR (CDCl 3): δ 8.10} (dd, J = 7.8Hz, 1.2Hz, 1H), 7.97 (d, J = 1.2Hz, 1H), 7.76 (d, J = 7.8Hz, 1H), 7.25 (d, J = 6.8 Hz, 1H), 6.78 (d, J = 6.8 Hz, 1H), 4.50 (t, J = 9.6 Hz, 2H), 4.11 (t, J = 9.6 Hz, 2H).
[4053] Examples 81 to 81 (1)
[4054] The compound of the present invention shown below was obtained by following the procedure of Example 52 while using the compound prepared in Example 45 (10) and Example 35 (63) instead of the compound prepared in Example 51 .
[4055] Example 81
[4056] 5-carboxy-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[4057]
[4058] TLC: Rf 0.22 (ethyl acetate: methanol = 2: 1);
[4059] _{NMR (DMSO-d 6):} δ 7.91 (d, J = 8.0Hz, 1H), 7.86-7.74 (m, 3H), 7.68-7.61 (m, 2H), 7.56 (d, J = 8.0Hz, 1H) , 5.68 (d, J = 8.5 Hz, 1H), 4.19 (d, J = 15.5 Hz, 1H), 4.01 (dd, J = 15.5, 8.5 Hz, 1H) 1H).
[4060] Example 81 (1)
[4061] 4-carboxy-3-phenylsulfonyl-2,3-dihydro-l, l-dioxide [
[4062]
[4063] Free body:
[4064] TLC: Rf 0.11 (CHCl 3: MeOH = 9: 1);
[4065] _{NMR (DMSO-d 6):} δ 13.78 (s, 1H), 8.24 (d, J = 7.5Hz, 1H), 8.05 (d, J = 7.8Hz, 1H), 7.91-7.84 (m, 1H), 7.82 2H), 6.27 (dd, J = 7.8, 2.1 Hz, 1 H), 4.20-3.95 (m, 2H), 7.69-7.61 (m, 2H).
[4066] Sodium salt:
[4067] TLC: Rf 0.11 (CHCl 3: MeOH = 9: 1);
[4068] _{NMR (DMSO-d 6):} δ 8.22 (dd, J = 7.4Hz and 1.4Hz, 1H), 7.95-7.85 (m , 3H), 7.85-7.70 (m, 2H), 7.70-7.55 (m, 2H) , 6.62 (dd, J = 8.0 Hz and 2.0 Hz, 1H), 4.10 (dd, J = 15 Hz and 8.0 Hz, 1H), 3.95 (dd, J = 15 Hz and 2.0 Hz, 1H).
[4069] Example 82
[4070] 4-Formyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide [
[4071]
[4072] Pyridinium dichromate (2.44 g) and magnesium sulfate (1.0 g) were added to a methylene chloride (40 ml) solution of the compound (1.46 g) prepared in Example 45 (20) and the mixture was stirred at room temperature for 6 hours. Insolubles were filtered off and discarded. To the filtrate was added 1N hydrochloric acid and extracted with methylene chloride. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was washed with methanol to obtain the compound (1.03 g) of the present invention having the following physical properties.
[4073] TLC: Rf 0.65 (CHCl 3: MeOH = 9: 1);
[4074] _{NMR (DMSO-d 6):} δ 10.29 (s, 1H), 8.29 (dd, J = 7.4, 1.2Hz, 1H), 8.16 (dd, J = 7.6, 1.2Hz, 1H), 8.03-7.92 (m, J = 8.0, 2.2 Hz, 1H), 4.08 (dd, J = 15.2, 8.0 Hz, 1H), 3.97 (m, 1H), 7.86-7.72 (dd, J = 15.2, 2.2 Hz, 1 H).
[4075] Examples 83 to 83 (3)
[4076] The compounds prepared in Example 73 (2), Example 73 (23), Example 28 (12) and Example 72 (5) were used instead of the compound prepared in Example 20 (27) The procedure of the present invention was the same as that of the present invention.
[4077] Example 83
[4078] 5-carboxymethyloxy-1,1-dioxo [b] thiophene
[4079]
[4080] TLC: Rf 0.18 (ethyl acetate: methanol = 5: 1);
[4081] _{NMR (DMSO-d 6):} δ 7.75 (dd, J = 8.3, 0.9Hz, 1H), 7.53 (dd, J = 6.9, 0.9Hz, 1H), 7.34 (d, J = 6.9Hz, 1H), 7.16 (d, J = 2.7 Hz, 1H), 7.07 (dd, J = 8.3, 2.7 Hz, 1H), 4.83 (s, 2H).
[4082] Example 83 (1)
[4083] 7-carboxymethyloxy-1,1-dioxo [b] thiophene
[4084]
[4085] TLC: Rf 0.21 (ethyl acetate: methanol = 4: 1);
[4086] _{NMR (DMSO-d 6):} δ 7.57 (t, J = 7.8Hz, 1H), 7.51 (d, J = 6.9Hz, 1H), 7.25 (d, J = 6.9Hz, 1H), 7.11 (d, J = 7.8 Hz, 2H), 4.92 (s, 2H).
[4087] Example 83 (2)
[4088] 4 - ((1S) -1-carboxy-2-methylpropyl) carbamoyl-1,1-dioxide benzo [b] thiophene
[4089]
[4090] TLC: Rf 0.16 (ethyl acetate: methanol = 4: 1);
[4091] _{NMR (DMSO-d 6):} δ 8.89 (d, J = 7.8Hz, 1H), 7.97 (d, J = 7.3Hz, 1H), 7.81 (d, J = 7.3Hz, 1H), 7.77 (d, J = 7.3 Hz, 1H), 7.69 (t, J = 7.3 Hz, 1H), 7.48 (d, J = 7.3 Hz, 1H), 4.33 (dd, J = 7.8, 6.0 Hz, 1H) , 0.97 (d, J = 6.6 Hz, 3H), 0.96 (d, J = 6.6 Hz, 3H).
[4092] Example 83 (3)
[4093] 4 - ((1 R) -1-carboxy-2-methylpropyl) carbamoyl-1,1-dioxide benzo [b] thiophene
[4094]
[4095] TLC: Rf 0.16 (ethyl acetate: methanol = 4: 1);
[4096] _{NMR (DMSO-d 6):} δ 8.89 (d, J = 7.8Hz, 1H), 7.97 (d, J = 7.3Hz, 1H), 7.81 (d, J = 7.3Hz, 1H), 7.77 (d, J = 7.3 Hz, 1H), 7.69 (t, J = 7.3 Hz, 1H), 7.47 (d, J = 7.3 Hz, 1H), 4.33 (dd, J = 7.8, 6.0 Hz, 1H) , 0.97 (d, J = 6.6 Hz, 3H), 0.96 (d, J = 6.6 Hz, 3H).
[4097] Example 84
[4098] 5- (3-Carboxypropyl) oxy-1, 1-dioxide benzo [b] thiophene
[4099]
[4100] Phosphate buffer (pH 7.4, 25 ml) and porcine liver esterase (100 μl) were added to a dimethylsulfoxide (5.0 ml) solution of the compound (98 mg) prepared in Example 73 (3) and the mixture was stirred at room temperature for 18 hours . The reaction mixture was diluted with 1N hydrochloric acid and extracted with ethyl acetate. The extract was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated to obtain the compound (90 mg) of the present invention having the following physical data.
[4101] TLC: Rf 0.26 (CHCl 3: MeOH = 9: 1);
[4102] _{NMR (CDCl 3): δ 7.62} (d, J = 8.4Hz, 1H), 7.13 (d, J = 6.8Hz, 1H), 6.95 (dd, J = 8.4, 2.2Hz, 1H), 6.85 (d, J = 2.2 Hz, 1H), 6.73 (d, J = 6.8 Hz, 1H), 4.10 (t, J = 6.2 Hz, 2H), 2.58 ).
[4103] Example 84 (1)
[4104] 5 - ((2E) -3-carboxy-2-propenyl) oxy-1,1-dioxide benzo [b] thiophene
[4105]
[4106] The procedure of Example 84 was followed except that the compound prepared in Example 30 (13) was used instead of the compound prepared in Example 73 (3) to obtain the compound of the present invention having the following physical data.
[4107] TLC: Rf 0.14 (CHCl 3: MeOH = 9: 1);
[4108] _{NMR (CD 3 OD): δ} 7.64 (d, J = 8.8Hz, 1H), 7.38 (d, J = 7.0Hz, 1H), 7.16-7.00 (m, 3H), 6.95 (d, J = 7.0Hz, 1H), 6.13 (dt, J = 15.8, 2.0 Hz, 1H), 4.89-4.80 (m, 2H).
[4109] Example 85
[4110] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[4111]
[4112] 4-phenylbutylamine (164 mg) and the compound (366 mg) prepared in Example 15 were dissolved in methylene chloride (3.0 ml), sodium sulfate (1.0 g) was added at room temperature, and the mixture was stirred for 1 hour. Sodium cyanoborohydride (63 mg), methanol (3.0 ml) and 4N hydrogen chloride dioxane solution (0.3 ml) were added to the reaction mixture, which was stirred for 1 hour at room temperature. The reaction mixture was concentrated. Chloroform was added to the residue, and insolubles were separated by filtration. The filtrate was concentrated. The residue was purified by silica gel column chromatography (chloroform: methanol = 100: 5) to obtain the compound (340 mg) of the present invention having the following physical data. In addition, the compound of the present invention having the following physical properties was also obtained by converting it into a hydrochloride salt by a known method.
[4113] Free body:
[4114] TLC: Rf 0.42 (CHCl 3: MeOH = 10: 1);
[4115] _{NMR (CDCl 3): δ 7.80-7.50} (m, 6H), 7.33-7.12 (m, 6H), 5.34 (d, J = 4.8Hz, 1H), 4.15-3.90 (m, 4H), 3.75 (s, 3H), 2.98 (t, J = 7.8 Hz, 2H), 2.63 (t, J = 7.8 Hz, 2H), 1.88-1.60 (m, 4H).
[4116] Hydrochloride:
[4117] TLC: Rf 0.42 (CHCl 3: MeOH = 10: 1);
[4118] _{NMR (CDCl 3): δ 9.49} (bs, 2H), 7.93 (d, J = 8.1Hz, 1H), 7.77-7.70 (m, 2H), 7.65 (t, J = 8.1Hz, 1H), 7.50 (t J = 8.1 Hz, 2H), 7.38-7.12 (m, 6H), 5.27 (d, J = 8.1 Hz, 1H), 4.18-4.02 , 3.88 (s, 3H), 3.85 (dd, J = 15.0, 8.1 Hz, 1H), 3.00-2.85 (m, 2H), 2.63 ).
[4119] Example 85 (1)
[4120] 3-ylmethyl) aminomethyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[4121]
[4122] The procedure of Example 85 was repeated using (pyridin-3-ylmethyl) amine instead of 4-phenylbutylamine and the compound prepared in Example 15 to obtain the compound of the present invention having the following physical data. In addition, the compound of the present invention having the following physical properties was also obtained by converting it into a hydrochloride salt by a known method.
[4123] Free body:
[4124] TLC: Rf 0.35 (CHCl 3: MeOH = 10: 1);
[4125] _{NMR (CDCl 3): δ 8.59} (d, J = 2.0Hz, 1H), 8.55 (dd, J = 4.8, 2.0Hz, 1H), 7.80-7.65 (m, 4H), 7.58 (d, J = 6.0Hz J = 7.6, 4.8 Hz, 1H), 5.20 (d, J = 8.2 Hz, 1H), 4.17 (d, J = 13.4 Hz, 1H), 3.95-3.70 (m, 5H), 3.80 (s, 3H).
[4126] Dihydrochloride:
[4127] TLC: Rf 0.35 (CHCl 3: MeOH = 10: 1);
[4128] _{NMR (DMSO-d 6):} δ 10.35 (brs, 1H), 10.15 (bs, 1H), 9.03 (s, 1H), 8.85 (d, J = 5.2Hz, 1H), 8.55 (d, J = 8.4Hz (M, 1H), 8.06 (d, J = 8.4 Hz, 1H), 7.95-7.72 (m, 4H), 7.70-7.55 ), 3.69 (s, 3H).
[4129] Example 86
[4130] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[4131]
[4132] The compound prepared in Example 35 (68) was used in place of the compound prepared in Example 7, and the procedure of Example 8 was followed to obtain the compound of the present invention having the following physical data.
[4133] TLC: Rf 0.48 (hexane: AcOEt = 1: 2);
[4134] _{NMR (DMSO-d 6):} δ 7.81-7.74 (m, 3H), 7.66-7.58 (m, 2H), 7.40 (d, J = 9.0Hz, 1H), 7.09 (dd, J = 9.0, 2.5Hz, J = 15.0, 9.5 Hz, 1H), 3.67 (dd, J = 15.0 Hz, 1H), 6.80 (d, , 3.0 Hz, 1 H), 2.99 (s, 6H).
[4135] Example 87
[4136] Carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene hydrochloride
[4137]
[4138] (2-dimethylaminoethyl) amine instead of the compound prepared in Example 81 (1) and (pyridin-3-ylmethyl) amine in place of 4-carboxy-1,1-dioxide benzo [b] thiophene The operation was carried out in the same manner as in Example 28, and further converted into a hydrochloride salt by a known method to give the following compounds of the present invention.
[4139] TLC: Rf 0.62 (chloroform: methanol: triethylamine = 8: 2: 1);
[4140] _{NMR (DMSO-d 6):} δ 10.40-10.20 (br, 1H), 9.19 (t, J = 5.4Hz, 1H), 8.13 (d, J = 6.9Hz, 1H), 7.94 (d, J = 7.5Hz , 7.87 (d, J = 7.8 Hz, 1H), 7.84-7.72 (m, 3H), 7.67-7.58 (m, 2H), 6.27 J = 9.0, 15.0 Hz, 1H), 3.96 (d, J = 15.0 Hz, 1H), 3.77-3.55 (m, 2H), 3.40-3.22 (m, 2H), 2.87-2.74 (m, 6H).
[4141] Examples 88 to 88 (2)
[4142] The procedure of Example 3 was repeated, except that the compound prepared in Example 18 (40), Example 20 (4) and Example 45 (3) was used instead of the compound prepared in Example 1, Chloro-benzoic acid instead of oxone, the following compounds of the present invention were obtained.
[4143] Example 88
[4144] 4,7-bis (pyridin-3-ylmethyloxy) -3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[4145]
[4146] TLC: Rf 0.36 (ethyl acetate: methanol = 2: 1);
[4147] _{NMR (CDCl 3): δ 8.65-8.60} (m, 3H), 8.57 (dd, J = 5.0, 1.5Hz, 1H), 7.90-7.80 (m, 2H), 7.68-7.65 (m, 2H), 7.60- J = 9.0 Hz, 1H), 6.98 (d, J = 9.0 Hz, 1H), 5.25 (d, J = 13.0 Hz, 1H), 7.51 (m, 1H), 7.41-7.31 (D, J = 12.0 Hz, 1H), 5.21 (dd, J = 9.5, 1.0 Hz, 1H), 5.20 ), 4.12 (dd, J = 15.0, 1.0 Hz, 1H), 3.75 (dd, J = 15.0, 9.5 Hz, 1H).
[4148] Example 88 (1)
[4149] 3-ylmethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[4150]
[4151] TLC: Rf 0.30 (ethyl acetate: methanol = 2: 1);
[4152] _{NMR (DMSO-d 6):} δ 8.29 (s, 1H), 8.20 (d, J = 6.2Hz, 1H), 7.73-7.57 (m, 4H), 7.51-7.31 (m, 6H), 5.77 (d, J = 8.8 Hz, 1H), 5.10 (d, J = 12.8 Hz, 1H), 4.90 15.0, 8.8 Hz, 1H).
[4153] Example 88 (2)
[4154] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[4155]
[4156] TLC: Rf 0.23 (ethyl acetate: methanol = 9: 1);
[4157] _{NMR (DMSO-d 6):} δ 8.11 (d, J = 6.9Hz, 2H), 7.79-7.72 (m, 3H), 7.65-7.60 (m, 3H), 7.34 (d, J = 7.5Hz, 1H) J = 15.0 Hz, 1H), 4.15-3.90 (m, 2H), 4.02 (dd, J = 15.0 , 8.5 Hz, 1H), 2.88-2.66 (m, 2H).
[4158] Example 89
[4159] Methoxy-3- (4-hydroxyphenyl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[4160]
[4161] The procedure of Example 1 was repeated except that 4-mercaptophenol was used instead of the compound prepared in Example 28 (27) and thiophenol instead of 1,1-dioxide benzo [b] thiophene to obtain the following material To give the compound of the present invention.
[4162] TLC: Rf 0.27 (hexane: AcOEt = 1: 1);
[4163] _{NMR (CDCl 3): δ 7.60-7.00} (m, 3H), 7.35 (d, J = 7.5Hz, 2H), 6.80 (d, J = 7.5Hz, 2H), 6.00 (s, 1H), 4.90 (dd , J = 5.0, 1.2 Hz, 1H), 3.90 (s, 3H), 3.75-3.50 (m, 2H).
[4164] Example 90
[4165] 3-ylmethyloxy) phenyl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[4166]
[4167] The procedure of Example 18 was repeated except that the compound prepared in Example 89 and the halide corresponding to 4-nitrobenzyl bromide were used instead of the compound prepared in Example 9 (12) to obtain To obtain a compound of the present invention.
[4168] TLC: Rf 0.22 (ethyl acetate).
[4169] Example 91
[4170] 3-ylmethyloxy) phenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene hydrochloride
[4171]
[4172] The compound prepared in Example 90 was used instead of the compound prepared in Example 1, and the compound of the present invention having the following physical properties was obtained by operating in the same manner as in Example 3.
[4173] TLC: Rf 0.39 (ethyl acetate: triethylamine = 95: 5);
[4174] _{NMR (DMSO-d 6):} δ 9.05 (br.s, 1H), 8.90 (d, J = 5.0Hz, 1H), 8.55 (d, J = 7.5Hz, 1H), 8.00 (dd, J = 7.5, J = 15 Hz, 1H), 4.00 (dd, J = 10 Hz, 1H), 7.80-8.60 (m, 3H), 7.50-7.15 (m, 4H), 5.60-5.40 15, 7.5 Hz, 1H), 3.45 (s, 3H).
[4175] Examples 92 to 92 (1)
[4176] The procedure of Example 1 was repeated using the compound prepared in Example 28 (27) and Example 28 (26) and thiophenol instead of 1,1-dioxide benzo [b] thiophene to obtain To obtain a compound of the present invention.
[4177] Example 92
[4178] Carbamoyl-4-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[4179]
[4180] TLC: Rf 0.40 (ethyl acetate: methanol: triethylamine = 8: 1: 1);
[4181] _{NMR (CDCl 3): δ 8.10} (d, J = 8.0Hz, 1H), 7.67 (br, 1H), 7.55-7.48 (m, 3H), 7.39-7.36 (m, 3H), 5.10 (dd, J = J = 14.0, 2.0 Hz, 1H), 3.57 (q, J = 6.0, 1H), 4.06 (s, 3H), 3.71 (dd, J = Hz, 2H), 2.53 (t, J = 6.0 Hz, 2H), 2.29 (s, 6H).
[4182] Example 92 (1)
[4183] 5-Pyridin-3-ylmethyl) carbamoyl-4-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[4184]
[4185] TLC: Rf 0.46 (ethyl acetate: methanol = 9: 1);
[4186] _{NMR (CDCl 3): δ 8.60-8.52} (m, 2H), 8.06 (d, J = 8.0Hz, 1H), 7.77-7.74 (m, 2H), 7.53-7.45 (m, 3H), 7.37-7.30 ( J = 6.0 Hz, 2H), 3.92 (s, 3H), 3.70 (dd, J = 14.0, 6.5 Hz, 1H) ), 3.58 (dd, J = 14.0, 2.0 Hz, 1 H).
[4187] Example 93
[4188] 4- (2- (piperidin-1-yl) ethyl) aminomethyl-1,1-dioxide benzo [b] thiophene
[4189]
[4190] (2-aminoethyl) piperidine was used instead of 4-bromomethyl-1,1-dioxide benzo [b] thiophene and 2,4-dimethoxybenzylamine hydrochloride. The compound of the present invention having the following physical properties was obtained. In addition, the compound of the present invention having the following physical properties was also obtained by converting it into a hydrochloride salt by a known method.
[4191] Free body:
[4192] TLC: Rf 0.16 (ethyl acetate: methanol: triethylamine = 90: 5: 5);
[4193] _{NMR (CDCl 3): δ 7.75-7.60} (m, 2H), 7.60-7.40 (m, 2H), 6.70 (d, J = 7.5Hz, 1H), 3.90 (s, 2H), 2.70 (t, J = 7.5 Hz, 2H), 2.50-2.20 (m, 4H), 2.40 (t, J = 7.5 Hz, 2H), 1.65-1.35 (m, 6H).
[4194] Dihydrochloride:
[4195] TLC: Rf 0.28 (ethyl acetate: methanol: triethylamine = 8: 1: 0.5);
[4196] NMR (DMSO-d ₆ + pyridine _{-d 5): δ 8.15 (d} , J = 7.5Hz, 1H), 8.00 (d, J = 7.5Hz, 1H), 7.90 (d, J = 7.5Hz, 1H), 2H), 3.55-3.30 (m, 4H), 3.30-3.10 (m, 4H), 1.90 (d, J = 7.5Hz, 1H) -1.70 (m, 4H), 1.65-1.50 (m, 2H).
[4197] Example 94
[4198] Ethyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[4199]
[4200] 5-methyl-l, l-dioxide By proceeding in the same manner as in Example 27 using the compound prepared in Example 93 instead of benzo [b] thiophene, the compound of the present invention having the following physical data was obtained. In addition, the compound of the present invention having the following physical properties was also obtained by converting it into a hydrochloride salt by a known method.
[4201] Free body:
[4202] TLC: Rf 0.18 (ethyl acetate: methanol: triethylamine = 90: 5: 5);
[4203] _{NMR (CDCl 3): δ 7.80-7.40} (m, 8H), 6.10 (d, J = 10Hz, 1H), 4.60 (d, J = 15Hz, 1H), 3.95 (d, J = 15Hz, 1H), 3.90 (d, J = 15 Hz, 1H), 3.75 (dd, J = 15,10 Hz, 1H), 2.80-2.60 (m, 2H), 2.60-2.20 (m, 6H), 1.60-1.30 (m, 6H).
[4204] Dihydrochloride:
[4205] TLC: Rf 0.30 (ethyl acetate: methanol: triethylamine = 8: 1: 0.5);
[4206] NMR (DMSO-d ₆ + pyridine _{-d 5): δ 8.35 (d} , J = 7.5Hz, 1H), 8.00-7.75 (m, 5H), 7.65 (t, J = 7.5Hz, 2H), 6.70 (d (D, J = 15 Hz, 1H), 4.20-3.95 (m, 2H), 3.65-3.35 (m, 4H), 3.30 -3.00 (m, 4H), 2.00-1.70 (m, 4H), 1.70-1.40 (m, 2H).
[4207] Example 95
[4208] 4-t-Butoxycarbonylaminobenzo [b] thiophene
[4209]
[4210] To a suspension of t-butanol (170 ml) of 4-carboxybenzo [b] thiophene (3.2 g) was added triethylamine (7.5 ml), diphenylphosphorylamide (4.2 ml) Lt; / RTI &gt; The precipitate was filtered, and the filtrate was concentrated. The residue was extracted with ethyl acetate. The extract was washed with water, dried over anhydrous magnesium sulfate and concentrated. The residue was purified by silica gel column chromatography (hexane: ethyl acetate = 5: 1) to obtain the compound of the present invention (3.0 g) having the following physical properties.
[4211] TLC: Rf 0.41 (hexane: AcOEt = 3: 1);
[4212] _{NMR (CDCl 3): δ 7.81-7.78} (m, 1H), 7.60 (d, J = 8.0Hz, 1H), 7.44-7.24 (m, 3H), 6.74 (br, 1H), 1.55 (s, 9H) .
[4213] Example 96
[4214] 4-t-Butoxycarbonylamino-1, 1-dioxo [b] thiophene
[4215]
[4216] Methanol and benzoic acid (8.2 g) were added to a chloroform (100 ml) solution of the compound (3.0 g) prepared in Example 95 at 0 ° C and the mixture was stirred at room temperature for 3 hours. The reaction mixture was concentrated. The residue was extracted with ethyl acetate. The extract was washed successively with an aqueous solution of sodium hydroxide, water and saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was dissolved in methylene chloride and allowed to stand overnight. The precipitated crystals were collected by filtration. The filtrate was concentrated. The residue was purified by silica gel column chromatography (methylene chloride) and combined with the above-mentioned crystals to obtain the compound (3.0 g) of the present invention having the following physical properties.
[4217] TLC: Rf 0.41 (hexane: AcOEt = 1: 1);
[4218] _{NMR (CDCl 3): δ 7.83-7.80} (m, 1H), 7.49 (t, J = 7.5Hz, 1H), 7.46-7.43 (m, 1H), 7.31 (dd, J = 7.2, 1.0Hz, 1H) , 6.70 (d, J = 7.2 Hz, 1H), 6.54 (br, 1H), 1.53 (s, 9H).
[4219] Example 97
[4220] 4-amino-1,1-dioxide benzo [b] thiophene hydrochloride
[4221]
[4222] A 4N hydrogen chloride-ethyl acetate solution (10 ml) was added to ethyl acetate (30 ml) of the compound (2.5 g) prepared in Example 96, and the mixture was stirred at room temperature for 3 hours. After the solvent was distilled off, the residue was washed with ethyl acetate to obtain the present compound (1.8 g) having the following physical properties.
[4223] TLC: Rf 0.29 (hexane: AcOEt = 1: 2);
[4224] _{NMR (CD 3 OD): δ} 7.63 (dd, J = 7.0, 1.0Hz, 1H), 7.61 (t, J = 7.5Hz, 1H), 7.54 (dt, J = 7.5, 1.0Hz, 1H), 7.42 ( dd, J = 7.5, 1.0 Hz, 1H), 7.08 (d, J = 7.0 Hz, 1H).
[4225] Example 98
[4226] Preparation of 4- (4-fluorobenzylcarbonylamino) -1,1-dioxo [b] thiophene
[4227]
[4228] To a solution of the compound prepared in Example 97 (100 mg), 4-fluorophenylacetic acid (192 mg) and triethylamine (1 ml) in dimethylformamide (3 ml) was added propane phosphoric acid cyclic anhydride (50% dimethylformamide 3 ml) was added, and the mixture was stirred at room temperature for 1.5 hours. Ethyl acetate was added to the reaction mixture, and the mixture was washed successively with water, a saturated aqueous solution of sodium hydrogencarbonate and saturated brine, and concentrated. The residue was purified by silica gel column chromatography (hexane: ethyl acetate = 1: 1) and then recrystallized from ethyl acetate-hexane to obtain the compound of the present invention having the following physical properties.
[4229] TLC: Rf 0.63 (ethyl acetate);
[4230] _{NMR (DMSO-d 6):} δ 10.27 (s, 1H), 7.88-7.82 (m, 1H), 7.64 (d, J = 7.0Hz, 1H), 7.61-7.55 (m, 2H), 7.41-7.34 ( m, 3H), 7.16 (t, J = 9.0 Hz, 2H), 3.75 (s, 2H).
[4231] Examples 98 (1) to 98 (5)
[4232] The compound prepared in Example 97 and the carboxylic acid derivative corresponding to 4-fluorophenylacetic acid were used in the same manner as in Example 98 to give the following compounds having the following physical data.
[4233] Example 98 (1)
[4234] 4- (Pyridin-3-ylcarbonyl) amino-1,1-dioxo [b] thiophene
[4235]
[4236] TLC: Rf 0.18 (ethyl acetate);
[4237] _{NMR (DMSO-d 6):} δ 10.69 (s, 1H), 9.17 (d, J = 2.0Hz, 1H), 8.80 (dd, J = 5.0, 2.0Hz, 1H), 8.34 (dt, J = 7.8, J = 7.5, 1.5 Hz, 1H), 7.72-7.63 (m, 3H), 7.60 (dd, J = 7.8, 5.0 Hz, 1H), 7.36 Hz, 1H).
[4238] Example 98 (2)
[4239] 4- (3-chlorobenzoyl) amino-1, 1-dioxide benzo [b] thiophene
[4240]
[4241] TLC: Rf 0.25 (hexane: AcOEt = 1: 1);
[4242] _{NMR (DMSO-d 6):} δ 10.62 (s, 1H), 8.07 (t, J = 1.5Hz, 1H), 7.96 (dt, J = 7.7, 1.5Hz, 1H), 7.78 (dd, J = 7.7, (D, J = 6.6 Hz, 1 H), 7.73-7.64 (m, 4H), 7.60 (t, J = 7.7 Hz, 1H).
[4243] Example 98 (3)
[4244] 4-Benzylcarbonylamino-1, 1-dioxo [b] thiophene
[4245]
[4246] TLC: Rf 0.45 (hexane: AcOEt = 1: 2);
[4247] _{NMR (CDCl 3): δ 7.75-7.72} (m, 1H), 7.48-7.35 (m, 7H), 7.29 (br, 1H), 6.79 (d, J = 7.2Hz, 1H), 6.58 (d, J = 7.2 Hz, 1 H), 3.79 (s, 2 H).
[4248] Example 98 (4)
[4249] 4- (Dimethylaminoacetyl) amino-1,1-dioxo [b] thiophene
[4250]
[4251] TLC: Rf 0.31 (ethyl acetate: methanol = 4: 1);
[4252] _{NMR (CDCl 3): δ 9.52} (br, 1H), 8.06 (m, 1H), 7.56-7.48 (m, 2H), 7.28-7.25 (m, 1H), 6.73 (d, J = 7.0Hz, 1H) , 3.15 (s, 2 H), 2.44 (s, 6 H).
[4253] Example 98 (5)
[4254] 4-acetylamino-l, l-dioxo [b] thiophene
[4255]
[4256] TLC: Rf 0.25 (ethyl acetate);
[4257] _{NMR (DMSO-d 6):} δ 10.05 (s, 1H), 7.89-7.83 (m, 1H), 7.70 (d, J = 7.0Hz, 1H), 7.61-7.55 (m, 2H), 7.33 (d, J = 7.0 Hz, 1H), 2.12 (s, 3H).
[4258] Examples 99 to 99 (10)
[4259] The title compound was prepared according to the method described in Example 28 using the corresponding amine derivative instead of 4-carboxy-1,1-dioxide benzo [b] thiophene (prepared in Example 107 below) and (pyridin- And, if necessary, converted into the corresponding salt by a known method to obtain the compound of the present invention having the following physical properties.
[4260] Example 99
[4261] 4- (3- (2-oxopyrrolidin-1-yl) propyl) carbamoyl-l, l-dioxide benzo [b] thiophene
[4262]
[4263] TLC: Rf 0.36 (CHCl 3: MeOH = 9: 1);
[4264] _{NMR (CDCl 3): δ 8.19} (dd, J = 7.0Hz and 1.0Hz, 1H), 8.05 (broad s, 1H), 7.95 (dd, J = 8.0Hz and 1.0Hz, 1H), 7.79 (d , J = 8.0 Hz, 1H), 7.60 (t, J = 8.0 Hz, 1H), 6.75 (d, J = 7.0 Hz, 1H), 3.50-3.35 (m, 6H) ), 2.20-2.00 (m, 2H), 1.90-1.70 (m, 2H).
[4265] Example 99 (1)
[4266] 4- (2-diethylaminoethyl) carbamoyl-l, l-dioxide benzo [b] thiophene
[4267]
[4268] TLC: Rf 0.20 (ethyl acetate: acetic acid: water = 3: 1: 1);
[4269] _{NMR (CDCl 3): δ 8.03} (dd, J = 7.2Hz and 1.0Hz, 1H), 7.79 (dt , J = 7.8Hz and 1.0Hz, 1H), 7.69 (dd , J = 7.8Hz and 1.0Hz, 1H ), 7.57 (t, J = 7.8 Hz, 1H), 6.77 (d, J = 7.2 Hz, 1H), 3.49 (m, 2H), 2.67 = 7.2 Hz, 4H), 1.04 (t, J = 7.2 Hz, 6H).
[4270] Example 99 (2)
[4271] (2- (N-ethyl-N- (3-methylphenyl) amino) ethyl) carbamoyl-1,1-dioxide benzo [b] thiophene
[4272]
[4273] TLC: Rf 0.61 (CHCl 3: MeOH = 9: 1);
[4274] _{NMR (CDCl 3): δ 7.91} (d, J = 7.0Hz, 1H), 7.74 (m, 1H), 7.55-7.40 (m, 2H), 7.13 (dd, J = 9.0Hz and 7.4Hz, 1H), (M, 4H), 3.19 (q, J = 7.0 Hz, 2H), 6.73 (d, J = 7.0 Hz, 1H), 6.70-6.55 2.29 (s, 3H), 1.16 (t, J = 7.0 Hz, 3H).
[4275] Example 99 (3)
[4276] Preparation of 4- (2,4,6-trimethoxybenzyl) carbamoyl-1,1-dioxide benzo [b] thiophene
[4277]
[4278] TLC: Rf 0.63 (CHCl 3: MeOH = 9: 1);
[4279] NMR (CDCl ₃ + DMSO-d ₆ ): 7.89 (d, J = 7.0 Hz, 1H), 7.80-7.65 = 7.0 Hz, 1H), 6.17 (s, 2H), 4.56 (d, J = 4.8 Hz, 2H), 3.84 (s, 6H), 3.82 (s, 3H).
[4280] Example 99 (4)
[4281] 4- (4- (2-hydroxyethyl) piperazin-1-yl) carbonyl-1,1-dioxide benzo [b] thiophene hydrochloride
[4282]
[4283] TLC: Rf 0.33 (methylene chloride: methanol = 10: 1);
[4284] _{NMR (DMSO-d 6):} δ 8.00-7.93 (m, 1H), 7.76-7.66 (m, 2H), 7.58 (d, J = 6.9Hz, 1H), 7.52 (d, J = 6.9Hz, 1H) , 5.40 (bs, 1H), 4.64-4.46 (m, 1H), 6.85-3.73 (m, 2H), 3.70-3.00 (m, 10H).
[4285] Example 99 (5)
[4286] 4- (4-benzyloxycarbonylpiperazin-1-yl) carbonyl-1, 1-dioxide benzo [b] thiophene
[4287]
[4288] TLC: Rf 0.64 (methylene chloride: methanol = 10: 1);
[4289] _{NMR (CDCl 3): δ 7.78} (d, J = 7.5Hz, 1H), 7.59 (t, J = 7.5Hz, 1H), 7.47 (d, J = 7.5Hz, 1H), 7.36 (s, 5H), 2H), 3.70-3.56 (m, 2H), 3.54 (d, J = 6.9Hz, 1H) -3.40 (m, 2H), 3.40-3.25 (m, 2H).
[4290] Example 99 (6)
[4291] (N-ethyl-N-2- (piperidin-1-yl) ethyl) carbamoyl-1,1-dioxide benzo [b] thiophene
[4292]
[4293] TLC: Rf 0.25 (CHCl 3: MeOH = 9: 1);
[4294] _{NMR (CDCl 3): δ 7.80-7.20} (m, 4H), 6.75 (d, J = 6.8Hz, 1H), 3.80-3.50 (m, 2H), 3.35-3.10 (m, 2H), 2.70-2.10 ( m, 6H), 1.70-1.20 (m, 6H), 1.26 and 1.06 (t, J = 7.0Hz, total 3H, respectively).
[4295] Example 99 (7)
[4296] 4- (3- (imidazol-1-yl) propyl) carbamoyl-1,1-dioxide benzo [b] thiophene
[4297]
[4298] TLC: Rf 0.43 (CHCl 3: MeOH = 4: 1);
[4299] _{NMR (CDCl 3): δ 7.95} (d, J = 7.0Hz, 1H), 7.72 (d, J = 7.6Hz, 1H), 7.69 (d, J = 7.6Hz, 1H), 7.52 (t, J = 7.6 (S, 1H), 6.76 (s, 1H), 6.76 (d, J = 7.0 Hz, 1H), 4.07 (t, J = 6.6 Hz, 2H), 3.44 (q, J = 6.6 Hz, 2H), 2.14 (m, 2H).
[4300] Example 99 (8)
[4301] Methyl-carbamoyl-l, l-dioxide &lt; / RTI &gt; benzo [b] thiophene
[4302]
[4303] TLC: Rf 0.30 (methylene chloride: methanol = 9: 1);
[4304] _{NMR (CDCl 3): δ 7.85-7.30} (m, 4H), 6.76 (d, J = 7.2Hz, 1H), 3.74 and 3.30 (each t, J = 6.0Hz, total 2H), 3.14 and 2.88 (each s , Total 3H), 2.70-2.10 (m, 6H), 1.70-1.30 (m, 6H).
[4305] Example 99 (9)
[4306] Yl) carbonyl-1,1-dioxo [b] thiophene [b] thiophene
[4307]
[4308] TLC: Rf 0.26 (ethyl acetate);
[4309] _{NMR (DMSO-d 6):} δ 8.00-7.92 (m, 1H), 7.74-7.65 (m, 2H), 7.56 (d, J = 6.9Hz, 1H), 7.52 (d, J = 6.9Hz, 1H) , 7.21 (s, 1H), 7.03-6.95 (m, 2H), 6.07 (s, 2H), 4.64-4.50 (m, 1H), 4.28-4.15 96 (m, 8H).
[4310] Example 99 (10)
[4311] 1-yl) carbonyl-1,1-dioxide benzo [b] thiophene hydrochloride
[4312]
[4313] TLC: Rf 0.10 (ethyl acetate);
[4314] _{NMR (DMSO-d 6):} δ 8.00-7.92 (m, 1H), 7.76-7.65 (m, 2H), 7.58 (d, J = 6.9Hz, 1H), 7.53-7.46 (m, 2H), 7.51 ( (d, J = 6.9 Hz, 1H), 7.45-7.28 (m, 3H), 6.84 (d, J = 15.3 Hz, 1H), 6.47-6.33 (m, 2 H), 3.70 - 2.97 (m, 8 H).
[4315] Examples 100 to 100 (24)
[4316] The procedure of Example 28 was repeated, except that the compound prepared in Example 81 (1) and the corresponding amine derivative were used instead of (pyridin-3-yl) ethylamine instead of 4-carboxy-1,1-dioxide benzo [b] thiophene And, if necessary, converted into the corresponding salt by a known method to obtain the compound of the present invention having the following physical properties.
[4317] Example 100
[4318] Yl) methyl] carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[4319]
[4320] TLC: Rf 0.43 (hexane: AcOEt = 1: 2);
[4321] _{NMR (DMSO-d 6):} δ 9.29 (t, J = 5.5Hz, 1H), 7.99 (d, J = 7.6Hz, 1H), 7.95 (d, J = 7.6Hz, 1H), 7.83 (t, J = 7.6 Hz, 1H), 7.79-7.76 (m, 3H), 7.67-7.60 (m, 3H), 6.48-6.35 (m, 2H), 6.25 J = 15.5, 5.5 Hz, 1H), 4.40 (dd, J = 15.5, 5.5 Hz, 1H), 4.10 (dd, J = 15.3, 9.0 Hz, 1H), 4.00 (d, J = 15.3 Hz, 1H).
[4322] Example 100 (1)
[4323] Carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[4324]
[4325] TLC: Rf 0.55 (ethyl acetate);
[4326] _{NMR (DMSO-d 6):} δ 8.40 (t, J = 4.8Hz, 1H), 7.89-7.86 (m, 2H), 7.86-7.69 (m, 4H), 7.67-7.58 (m, 2H), 6.25 ( s, 2H), 6.18 (dd, J = 8.1, 2.1 Hz, 1H), 4.46-4.30 (m, 2H), 4.11-3.94 (m, 2H), 3.77 (s, 9H).
[4327] Example 100 (2)
[4328] Carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[4329]
[4330] TLC: Rf 0.44 (ethyl acetate: methanol = 2: 1);
[4331] _{NMR (CDCl 3): δ 8.20-8.08} (m, 1H), 8.02 (d, J = 7.5Hz, 1H), 7.83-7.62 (m, 5H), 7.59-7.49 (m, 2H), 6.40 (dd, 2H), 3.32-3.20 (m, 1H), 3.20-3.06 (m, 1H), 2.53-2.33 (m, m, 2H), 2.15-1.88 (m, 3H), 1.85-1.74 (m, 1H).
[4332] Example 100 (3)
[4333] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene (3S)
[4334]
[4335] High polarity:
[4336] TLC: Rf 0.27 (methanol: ethyl acetate: triethylamine = 1: 8: 0.05);
[4337] _{NMR (CDCl 3): δ 7.90-7.80} (m, 4H), 7.75-7.66 (m, 2H), 7.62-7.53 (m, 2H), 7.37-7.13 (m, 5H), 6.70 (d, J = 8.7 J = 15.0, 1.5 Hz, 1H), 3.68 (d, J = 12.9 Hz, 1H), 3.63 (m, (dd, J = 15.0,9.3 Hz, 1H), 3.57 (d, J = 12.9 Hz, 1H), 3.00-2.86 (m, 2H), 2.72 (dd, J = 9.9, 6.3 Hz, 1H) 2.31 (m, 2 H), 1.89-1.77 (m, 1 H).
[4338] Low polarity:
[4339] TLC: Rf 0.35 (methanol: ethyl acetate: triethylamine = 1: 8: 0.05);
[4340] _{NMR (CDCl 3): δ 7.94-7.87} (m, 2H), 7.87-7.78 (m, 2H), 7.75-7.66 (m, 2H), 7.64-7.56 (m, 2H), 7.41-7.23 (m, 5H ), 6.73 (d, J = 8.1 Hz, IH), 6.28-6.21 (m, IH), 4.71-4.59 (m, IH), 3.80 (dd, J = 14.7, 1.2 Hz, 2H), 3.62 (dd, J = 14.7, 9.3 Hz, 1H), 2.95-2.84 (m, 1H), 2.80-2.67 (m, 2H), 2.46-2.30 1H).
[4341] * Is not determined, but the above-mentioned higher polar body and lower polar body are each a single optically active substance.
[4342] Example 100 (4)
[4343] Yl) ethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[4344]
[4345] Free body:
[4346] TLC: Rf 0.33 (ethyl acetate: methanol: triethylamine = 4: 2: 0.5);
[4347] _{NMR (CDCl 3): δ 7.93-7.78} (m, 4H), 7.75-7.66 (m, 2H), 7.63-7.53 (m, 2H), 7.10 (brs, 1H), 6.31-6.24 (m, 1H), (M, 3H), 2.80 (t, J = 5.7 Hz, 2H), 2.69-2.53 (m, 4H), 1.86-1.73 (m, 4H).
[4348] Hydrochloride:
[4349] TLC: Rf 0.37 (ethyl acetate: methanol: triethylamine = 4: 2: 0.5);
[4350] _{NMR (DMSO-d 6):} δ 9.18 (t, J = 5.4Hz, 1H), 8.14 (d, J = 7.5Hz, 1H), 7.96-7.90 (m, 1H), 7.85 (t, J = 7.5Hz J = 9.3 Hz, 1H), 4.13 (dd, J = 15.6, 9.3 Hz, 1H), 3.96 (m, 1H), 7.81-7.72 d, J = 15.6 Hz, 1H), 3.78-3.50 (m, 4H), 3.48-3.28 (m, 2H), 3.06-2.94 (m, 2H), 2.09-1.
[4351] Example 100 (5)
[4352] Carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[4353]
[4354] Free body:
[4355] TLC: Rf 0.47 (ethyl acetate: methanol: triethylamine = 4: 2: 0.5);
[4356] _{NMR (CDCl 3): δ 7.92-7.80} (m, 4H), 7.76-7.66 (m, 2H), 7.62-7.56 (m, 2H), 7.03 (brs, 1H), 6.29 (dd, J = 9.0, 1.5 J = 7.2 Hz, 4H), 3.72 (d, J = 14.4,1.5 Hz, 1H), 3.72-3.44 ), 1.04 (t, J = 7.2 Hz, 6H).
[4357] Hydrochloride:
[4358] TLC: Rf 0.49 (ethyl acetate: methanol: triethylamine = 4: 2: 0.5);
[4359] _{NMR (DMSO-d 6):} δ 10.32 (brs, 1H), 9.30-9.20 (m, 1H), 8.08 (d, J = 7.5Hz, 1H), 7.94 (d, J = 7.5Hz, 1H), 7.86 (d, J = 7.5 Hz, 1H), 7.82-7.72 (m, 3H), 7.68-7.58 (m, 2H), 6.29 (d, J = 9.3 Hz, 1H) Hz, 1H), 3.96 (d, J = 15.6 Hz, 1H), 3.80-3.57 (m, 2H), 3.40-3.08 (m, 6H), 1.24 (t, J = 7.2 Hz, 6H).
[4360] Example 100 (6)
[4361] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene (2-methyl-
[4362]
[4363] Free body:
[4364] TLC: Rf 0.49 (ethyl acetate: triethylamine = 6: 0.5);
[4365] _{NMR (CDCl 3): δ 7.94-7.87} (m, 2H), 7.82 (d, J = 6.9Hz, 1H), 7.75-7.67 (m, 1H), 7.67-7.54 (m, 4H), 7.17-7.11 ( (m, 2H), 6.56 (d, J = 7.8 Hz, 1H), 6.49 (br s, 1H), 6.26 (dd, J = 9.0, 1.2 Hz, 1H), 3.81 J = 7.2 Hz, 2H), 2.30 (s, 3H), 1.15 (t, J = 7.2Hz, 1H), 3.77-3.47 3H).
[4366] Hydrochloride:
[4367] TLC: Rf 0.47 (ethyl acetate: triethylamine = 6: 0.5);
[4368] _{NMR (CD 3 OD): δ} 7.98-7.60 (m, 6H), 7.59-7.26 (m, 6H), 6.36-6.15 (m, 1H), 4.09-3.89 (m, 4H), 3.88-3.40 (m, 4H), 2.44 (s, 3H), 1.17 (t, J = 7.2 Hz, 3H).
[4369] Example 100 (7)
[4370] 3-Phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[4371]
[4372] Free body:
[4373] TLC: Rf 0.29 (methylene chloride: methanol = 6: 1);
[4374] _{NMR (CDCl 3): δ 8.00-7.55} (m, 8H), 5.85 (d, J = 8Hz, 1H), 3.85-3.30 (m, 6H), 2.85-2.50 (m, 2H), 2.55 (m, 2H ), 2.40 (m, 2H), 1.80-1.40 (m, 6H), 1.34 and 1.36 (t, J = 7 Hz, total 3H, respectively).
[4375] Hydrochloride:
[4376] TLC: Rf 0.29 (methylene chloride: methanol = 6: 1);
[4377] NMR (CDCl ₃ + DMSO-d ₆ ): 11.30 (broad s, 1H), 7.95-7.60 (m, 8H), 5.89 (d, J = 8 Hz, 1H), 4.20-3.80 2H), 2.10 (m, 2H), 2.00 (m, 3H), 1.50 (m, 1H), 1.41 (t, J = 7 Hz, 3H).
[4378] Example 100 (8)
[4379] Propyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[4380]
[4381] Free body:
[4382] TLC: Rf 0.50 (methylene chloride: methanol = 4: 1);
[4383] _{NMR (CDCl 3): δ 7.90-7.50} (m, 9H), 7.56 (s, 1H), 6.98 (s, 1H), 6.93 (s, 1H), 6.27 (dd, J = 2Hz and 7Hz, 1H), 4.20-3.95 (m, 2H), 3.80-3.55 (m, 3H), 3.30 (m, 1H), 2.13 (m, 2H).
[4384] Hydrochloride:
[4385] TLC: Rf 0.50 (methylene chloride: methanol = 4: 1);
[4386] NMR (CDCl ₃ + DMSO-d ₆ ): δ 9.59 (s, 1H), 9.49 (t-form, 1H), 8.23 (t, J = 4.4 Hz, 1H), 7.85-7.60 (M, 2H), 3.82 (m, 2H), 3.65 (m, 2H) 1H), 3.25 (m, IH), 2.40 (m, IH), 2.20 (m, IH).
[4387] Example 100 (9)
[4388] 4 - ((3R) -1-Benzylpyrrolidin-3-yl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-
[4389]
[4390] Low polarity:
[4391] TLC: Rf 0.35 (methanol: ethyl acetate: triethylamine = 1: 8: 0.05);
[4392] _{NMR (CDCl 3): δ 7.94-7.87} (m, 2H), 7.87-7.78 (m, 2H), 7.75-7.67 (m, 2H), 7.64-7.56 (m, 2H), 7.38-7.26 (m, 5H ), 6.68 (d, J = 8.1 Hz, 1H), 6.28-6.20 (m, 1H), 4.73-4.59 (m, 1H), 3.80 (dd, J = 14.7,1.5Hz, 1H) 2H), 3.63 (dd, J = 14.7, 9.3 Hz, 1H), 2.96-2.87 (m, 1H), 2.82-2.66 (m, 2H), 2.47-2.30 1H).
[4393] High polarity:
[4394] TLC: Rf 0.27 (methanol: ethyl acetate: triethylamine = 1: 8: 0.05);
[4395] _{NMR (CDCl 3): δ 7.90-7.78} (m, 4H), 7.74-7.65 (m, 2H), 7.62-7.52 (m, 2H), 7.36-7.13 (m, 5H), 6.79 (d, J = 8.4 J = 15.0, 1.5 Hz, 1H), 3.65 (d, J = 12.9 Hz, 1H), 3.62 (m, 1H) (dd, J = 15.0, 9.0 Hz, 1H), 3.54 (d, J = 12.9 Hz, 1H), 2.96-2.83 (m, 2H), 2.72 (dd, J = 9.9, 6.3 Hz, 1H) 2.32 (m, 2H), 1.90 - 1.73 (m, 1H).
[4396] * Is not determined, but the above-mentioned higher polar body and lower polar body are each a single optically active substance.
[4397] Example 100 (10)
[4398] Propyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[4399]
[4400] Free body:
[4401] TLC: Rf 0.25 (methanol: ethyl acetate: triethylamine = 2: 4: 0.5);
[4402] _{NMR (CDCl 3): δ 9.16-9.06} (m, 1H), 7.91-7.84 (m, 2H), 7.84-7.77 (m, 2H), 7.75-7.62 (m, 2H), 7.61-7.53 (m, 2H ), 6.44-6.37 (m, 1H), 3.85 (dd, J = 14.7,1.2Hz, 1H), 3.80-3.61 (m, 2H), 3.59-3.44 ), 2.71-2.59 (m, 4H), 2.00-1.63 (m, 6H).
[4403] Hydrochloride:
[4404] TLC: Rf 0.26 (methanol: ethyl acetate: triethylamine = 2: 4: 0.5);
[4405] _{NMR (DMSO-d 6):} δ 10.43 (brs, 1H), 9.00 (t, J = 5.7Hz, 1H), 8.02 (d, J = 7.5Hz, 1H), 7.94 (d, J = 7.5Hz, 1H ), 7.90-7.74 (m, 4H), 7.71-7.61 (m, 2H), 6.30 (d, J = 9.0 Hz, 1 H), 4.11 (dd, J = 15.0, 9.0 Hz, J = 15.0 Hz, 1H), 3.60-3.10 (m, 6H), 3.10-2.78 (m, 2H), 2.11-1.73 (m, 6H).
[4406] Example 100 (11)
[4407] Methyl-carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[4408]
[4409] Free body:
[4410] TLC: Rf 0.29 (methylene chloride: methanol = 6: 1);
[4411] _{NMR (CDCl 3): δ 8.05-7.55} (m, 8H), 5.88 (dd, J = 8.8Hz and 2.0Hz, 1H), 4.00-3.55 and 3.30 (each m, total 4H), 3.20 and 3.17 (each s , Total 3H), 2.80-2.35 (m, 6H), 1.70-1.40 (m, 6H).
[4412] Hydrochloride:
[4413] TLC: Rf 0.29 (methylene chloride: methanol = 6: 1);
[4414] _{NMR (DMSO-d 6):} δ 10.49 (broad s, 1H), 8.15 (d, J = 6.2Hz, 1H), 8.00-7.60 (m, 7H), 5.87 (d, J = 8.8Hz, 1H), (M, 4H), 3.70-2.80 (m, 6H), 3.33 and 3.16 (s, total 3H), 2.00-1.60 (m, 5H), 1.44 (m, 1H).
[4415] Example 100 (12)
[4416] Carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[4417]
[4418] TLC: Rf 0.45 (methylene chloride: ethyl acetate = 4: 1);
[4419] _{NMR (DMSO-d 6):} δ 9.26 (t, J = 5.8Hz, 1H), 7.78 (d, J = 7.6Hz, 1H), 7.91 (dd, J = 7.6, 1.0Hz, 1H), 7.84 (dd J = 7.0 Hz, 1H), 6.51 (d, J = 2.2 Hz, 2H), 6.39 (t, J = 2.2 Hz, 1H), 4.42 (d, J = 5.8 Hz, 2H), 3.73 (s, 6H).
[4420] Example 100 (13)
[4421] Propyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene hydrochloride
[4422]
[4423] TLC: Rf 0.30 (ethyl acetate: methanol: triethylamine = 8: 1.5: 0.5);
[4424] _{NMR (DMSO-d 6):} δ 10.40 (broad s, 1H), 9.08 (t, J = 5.3Hz, 1H), 8.10-7.60 (m, 8H), 6.33 (d, J = 9.2Hz, 1H), J = 15.0 Hz, 1H), 3.60-3.00 (m, 6H), 2.80 (m, 2H), 2.05 (t, J = 6.5 Hz), 4.13 (dd, J = 15.0 Hz and 9.2 Hz, Hz, 2 H), 1.73 (m, 5 H), 1.36 (m, 1 H).
[4425] Example 100 (14)
[4426] Carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene hydrochloride
[4427]
[4428] TLC: Rf 0.46 (ethyl acetate: methanol: triethylamine = 8: 1.5: 0.5);
[4429] _{NMR (DMSO-d 6):} δ 10.01 (s, 1H), 9.27 (t, J = 5.7Hz, 1H), 8.09 (d, J = 7.0Hz, 1H), 7.97 (d, J = 7.0Hz, 1H J = 7.0 Hz, 1H), 7.80-7.76 (m, 3H), 7.68-7.60 (m, 2H), 6.36 (d, J = 15.3 Hz, 1H), 3.90-3.60 (m, 4H), 3.33 (m, J = 6.6 Hz, 3H), 1.38 (d, J = 6.6 Hz, 3H), 1.34 (d, J = 6.6 Hz, 3H).
[4430] Example 100 (15)
[4431] Yl) ethyl] carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide-benzo [b] thiophene hydrochloride
[4432]
[4433] TLC: Rf 0.33 (ethyl acetate: methanol: triethylamine = 8: 1.5: 0.5);
[4434] _{NMR (DMSO-d 6):} δ 11.14 (broad s, 1H), 9.27 (broad t- type, 1H), 8.13 (d, J = 7.5Hz, 1H), 7.93 (d, J = 7.5Hz, 1H) , 7.86 (t, J = 7.5 Hz, 1H), 7.82-7.70 (m, 3H), 7.70-7.60 (m, 2H), 6.30 (d, J = 8.4 Hz, Hz and 8.4 Hz, 1 H), 4.00-3.65 (m, 7H), 3.65-3.00 (m, 6H).
[4435] Example 100 (16)
[4436] Propyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene · Hydrochloride
[4437]
[4438] TLC: Rf 0.47 (ethyl acetate: methanol: triethylamine = 8: 1.5: 0.5);
[4439] _{NMR (DMSO-d 6):} δ 10.70 and 10.66 (respectively, broad s, total 1H), 8.00-7.65 (m, 8H ), 5.83 (d, J = 8.7Hz, 1H), 4.14 (dd, J = 15.3Hz 2H), 2.00-1.60 (m, 6H), 1.40 (m, IH), 4.00-3.70 (m, 3H) 0.98 and 0.86 (t, J = 7.2 Hz, total 3H, respectively).
[4440] Example 100 (17)
[4441] Carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene Opene · hydrochloride
[4442]
[4443] TLC; Rf 0.55 (ethyl acetate: methanol: triethylamine = 8: 1.5: 0.5);
[4444] _{NMR (DMSO-d 6):} δ 10.78 (broad s, 1H), 8.00-7.60 (m, 8H), 5.90 (d, J = 9.2Hz, 1H), 4.40-4.03 (m, 3H), 4.00-2.80 (m, 8H), 2.00-1.60 (m, 5H), 1.40 (m, 1H), 1.44 and 1.28, total 6H).
[4445] Example 100 (18)
[4446] Benzoylpiperazin-1-yl) carbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[4447]
[4448] TLC: Rf 0.48 (methylene chloride: methanol = 10: 1);
[4449] NMR (DMSO-d ₆ ): 7.95-7.80 (m, 3H), 7.80-7.56 (m, 5H), 7.42 (s, 5H), 5.92 (dd, J = 9.0, 1.5 Hz, 4.00 (m, 2H), 3.90-3.40 (m, 6H), 3.72 (dd, J = 15.0, 1.5 Hz, 1H), 3.65 (dd, J = 15.0, 9.0Hz, 1H).
[4450] Example 100 (19)
[4451] Yl) carbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene hydrochloride
[4452]
[4453] TLC: Rf 0.55 (methylene chloride: methanol = 10: 1);
[4454] _{NMR (DMSO-d 6):} δ 7.88-7.73 (m, 6H), 7.67-7.63 (m, 2H), 7.47 (d, J = 7.0Hz, 2H), 7.21 (d, J = 7.0Hz, 2H) , 5.87 (dd, J = 10.0,1.5 Hz, 1H), 4.16 (bs, 2H), 4.05 (dd, J = 15.0, 10.0HZ, 3.30-2.90 (m, 8H), 2.58 (q, J = 8.0 Hz, 2H), 1.17 (t, J = 8.0 Hz, 3H).
[4455] Example 100 (20)
[4456] 1-yl) carbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene hydrochloride
[4457]
[4458] TLC: Rf 0.55 (methylene chloride: methanol = 10: 1);
[4459] _{NMR (DMSO-d 6):} δ 7.88-7.78 (m, 3H), 7.78-7.72 (m, 3H), 7.67-7.58 (m, 7H), 7.48-7.41 (m, 3H), 7.38-7.34 (m (Dd, J = 15.5, 9.5 Hz, 1H), 3.79 (d, J = 15.5 Hz, 1 H), 3.19 (s, 2H).
[4460] Example 100 (21)
[4461] 1-yl) carbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene- ] Thiophene hydrochloride
[4462]
[4463] TLC: Rf 0.54 (methylene chloride: methanol = 10: 1);
[4464] _{NMR (DMSO-d 6):} δ 7.86-7.76 (m, 4H), 7.74 (d, J = 8.0Hz, 2H), 7.64 (t, J = 8.0Hz, 2H), 7.08 (bs, 1H), 6.98 2H), 5.86 (d, J = 8.5 Hz, 1H), 4.15-3.70 (m, 2H), 6.96 (d, 4.04 (dd, J = 15.0, 8.5 Hz, 1H), 3.78 (d, J = 15.0 Hz, 1H), 3.15-2.80 (m, 8H).
[4465] Example 100 (22)
[4466] Carbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[4467]
[4468] TLC: Rf 0.80 (methylene chloride: methanol = 10: 1);
[4469] _{NMR (DMSO-d 6):} δ 7.96-7.80 (m, 4H), 7.76 (d, J = 7.5Hz, 2H), 7.66 (t, J = 7.5Hz, 2H), 7.45-7.36 (m, 5H) , 5.89 (d, J = 8.7 Hz, 1H), 5.11 (s, 2H), 4.13 (dd, J = 14.7, 8.7 Hz, 1H), 3.93 (d, J = 14.7 Hz, 1H), 3.80-3.40 m, 8H).
[4470] Example 100 (23)
[4471] 1-yl) carbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene hydrochloride
[4472]
[4473] TLC: Rf 0.80 (methylene chloride: methanol = 10: 1);
[4474] _{NMR (DMSO-d 6):} δ 7.97-7.90 (m, 2H), 7.90-7.74 (m, 4H), 7.74-7.63 (m, 2H), 7.23-7.10 (m, 2H), 7.10-6.83 (m J = 15.3 Hz, 1H), 3.92-3.80 (m, 2H), 5.92 (d, J = 9.6 Hz, , 3.08-2.90 (m, 6H), 2.30 (s, 3H).
[4475] Example 100 (24)
[4476] 1-yl) carbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene hydrochloride
[4477]
[4478] TLC: Rf 0.75 (methylene chloride: methanol = 10: 1);
[4479] _{NMR (DMSO-d 6):} δ 8.02-7.92 (m, 2H), 7.92-7.73 (m, 4H), 7.72-7.64 (m, 2H), 7.36-7.14 (m, 2H), 7.00-6.90 (m J = 15.3 Hz, 1H), 5.91 (d, J = 9.6 Hz, 1H), 4.20-3.76 (m, 4H), 4.14 (dd, J = , 3.72 (s, 3H), 3.45 - 3.26 (m, 4H).
[4480] Examples 101 to 101 (1)
[4481] The procedure of Example 1 was repeated using the compound prepared in Example 28 (11) or 73 (16) instead of 1,1-dioxo [b] thiophene to obtain the following compound of the present invention .
[4482] Example 101
[4483] Yl) ethyl) carbamoyl-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[4484]
[4485] TLC: Rf 0.40 (methanol: water: acetic acid = 1: 1: 0.1);
[4486] _{NMR (CDCl 3): δ 7.81} (dd, J = 7.6, 1.1Hz, 1H), 7.75 (dd, J = 7.6, 1.1Hz, 1H), 7.61 (t, J = 7.6Hz, 1H), 7.56-7.53 (m, 2H), 7.38-7.35 (m, 3H), 6.91 (br, IH), 5.74 (dd, J = 7.3, 1.3 Hz, 2H), 2.38 (br, 4H), 3.65-3.58 (m, 1H), 3.60 (dd, J = 13.9,1.3Hz, 1H), 3.55-3.45 , 1.56-1.48 (m, 4H), 1.44-1. 39 (m, 2H).
[4487] Example 101 (1)
[4488] 3-phenylthio-l, l-dioxide &lt; / RTI &gt; benzo [b] thiophene
[4489]
[4490] TLC: Rf 0.30 (hexane: AcOEt = 1: 1);
[4491] _{NMR (CDCl 3): δ 8.54} (ddd, J = 4.8, 1.7, 1.0Hz, 1H), 7.54 (dt, J = 7.7, 1.7Hz, 1H), 7.49 (t, J = 8.0Hz, 1H), 7.43 J = 6.6 Hz, 2H), 7.34-7.22 (m, 5H), 7.15-7.10 (m, 2H), 4.91 (dd, ), 3.66 (dd, J = 13.8, 6.9 Hz, 1H), 3.57 (dd, J = 13.8, 1.8 Hz, 1H), 3.31 (t, J = 6.6 Hz, 2H).
[4492] Example 102
[4493] Carbamoyl-3- (4-nitrophenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[4494]
[4495] According to the same manner as that of Example 27 using 5-methyl-1,1-dioxide benzo [b] thiophene instead of the compound prepared in Example 28 (11) and sodium benzenesulfonate sodium salt in place of benzenesulfonic acid sodium salt And the compound of the present invention having the following physical properties was obtained by conversion into the hydrochloride salt by a known method.
[4496] Free body:
[4497] TLC: Rf 0.40 (methanol: water: acetic acid = 5: 5: 0.5);
[4498] _{NMR (CDCl 3): δ 8.35} (d, J = 8.7Hz, 2H), 8.01 (d, J = 8.7Hz, 2H), 7.91 (dd, J = 7.5, 1.7Hz, 1H), 7.81 (dd, J = 7.5, 1.7 Hz, 1H), 7.76 (t, J = 7.5 Hz, 1H), 7.59 (br, 1H), 6.42 (dd, J = 9.2, 1.5 Hz, 1H) 1H), 3.75 (dd, J = 15.0, 9.2 Hz, 1H), 3.75-3.64 (m, 1H), 3.57-3.48 (m, 1H), 2.77-2.65 , 4H), 1.66 - 1.57 (m, 4H), 1.52 - 1.45 (m, 2H).
[4499] Hydrochloride:
[4500] TLC: Rf 0.40 (methanol: water: acetic acid = 5: 5: 0.5);
[4501] _{NMR (DMSO-d 6):} δ 9.98 (br, 1H), 9.28 (br, 1H), 8.42 (d, J = 8.7Hz, 2H), 8.11 (d, J = 7.5Hz, 1H), 8.03 (d J = 7.5 Hz, 1H), 6.41 (dd, J = 7.3, 3.2 Hz, 1H), 4.16 (dd, J = 2H), 3.57-3.48 (m, 2H), 3.32-3.25 (m, 2H, J = 15.5, 7.3Hz, 1H), 4.10 (dd, J = 15.5,3.2Hz, 1H), 3.72-3.70 ), 2.96 (br, 2H), 1.82-1.68 (m, 5H), 1.45-1.35 (m, 1H).
[4502] Examples 103 to 103 (41)
[4503] Instead of 4-bromomethyl-1,1-dioxide benzo [b] thiophene, 4-methylsulfonyloxymethyl-3-phenylsulfonyl-2,3-dihydro- And the amine derivative corresponding to 2,4-dimethoxybenzylamine hydrochloride was used in place of the compound represented by the above-mentioned formula, and, if necessary, converted into the corresponding salt by a known method, Of the present invention.
[4504] Example 103
[4505] Methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene Dihydrochloride
[4506]
[4507] TLC: Rf 0.48 (methanol: ethyl acetate: triethylamine = 2: 8: 0.5);
[4508] _{NMR (CD 3 OD + D 2} O (4 drops)): δ 8.16 (d, J = 7.5Hz, 1H), 7.90 (t, J = 7.5Hz, 1H), 7.85-7.73 (m, 4H), 7.64 (M, 2H), 6.18-6.10 (m, 1H), 4.93 (d, J = 14.4 Hz, 1H), 4.60 1H), 3.84 (dd, J = 15.6, 0.9 Hz, 1H), 3.72-3.00 (m, 8H), 2.74 (s, 3H), 2.00 - 1.55 (m, 6H).
[4509] Example 103 (1)
[4510] Amino-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene dihydrochloride
[4511]
[4512] TLC: Rf 0.45 (ethyl acetate: triethylamine = 6: 0.5);
[4513] _{NMR (DMSO-d 6):} δ 9.64 (brs, 2H), 8.21 (d, J = 6.3Hz, 1H), 7.89-7.74 (m, 5H), 7.67-7.58 (m, 2H), 7.18-7.04 ( (m, 1H), 6.96-6.50 (m, 3H), 6.46 (dd, J = 6.9, 3.0Hz, 1H), 4.73-4.59 (m, 2H), 3.80-3.58 (m, 2H), 3.50-3.33 (m, 2H), 3.29-3.10 .
[4514] Example 103 (2)
[4515] 4- (N-benzyl-N-ethyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene hydrochloride
[4516]
[4517] TLC: Rf 0.67 (ethyl acetate: triethylamine = 6: 0.5);
[4518] NMR (CD ₃ OD + pyridine _{-d 5): δ 7.92 (d} , J = 7.2Hz, 1H), 7.71-7.58 (m, 4H), 7.57-7.45 (m, 3H), 7.32-7.15 (m, 5H) , 5.84 (dd, J = 8.4, 1.8 Hz, 1H), 4.33 (d, J = 14.7 Hz, 1H), 3.90-3.62 q, J = 7.2 Hz, 2H), 1.14 (t, J = 7.2 Hz, 3H).
[4519] Example 103 (3)
[4520] 4- (2-diethylaminoethyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene dihydrochloride
[4521]
[4522] TLC: Rf 0.35 (methanol: ethyl acetate: triethylamine = 2: 8: 0.5);
[4523] _{NMR (DMSO-d 6):} δ 10.66 (brs, 1H), 9.96 (brs, 1H), 9.76 (brs, 1H), 8.26-8.26 (m, 1H), 7.91-7.74 (m, 5H), 7.67- 2H), 3.70-3.37 (m, 4H, m), 7.57 (m, 2H), 6.54-6.45 ), 3.28-3.10 (m, 4H), 1.26 (t, J = 7.2 Hz, 6H).
[4524] Example 103 (4)
[4525] 4- (4-methylbenzyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene hydrochloride
[4526]
[4527] TLC: Rf 0.47 (ethyl acetate: triethylamine = 6: 0.5);
[4528] _{NMR (DMSO-d 6):} δ 9.83 (brs, 1H), 9.54 (brs, 1H), 8.16 (d, J = 6.9Hz, 1H), 7.89-7.75 (m, 3H), 7.75-7.68 (m, J = 8.1 Hz, 2H), 7.28 (d, J = 8.1 Hz, 2H), 6.29 (dd, J = 4.8, 3.9 Hz, 1H) 2H), 3.93-3.80 (m, 2H), 2.32 (s, 3H).
[4529] Example 103 (5)
[4530] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene Dihydrochloride
[4531]
[4532] TLC: Rf 0.47 (methanol: ethyl acetate: triethylamine = 2: 8: 0.5);
[4533] _{NMR (CD 3 OD + D 2} O (1 drop)): δ 8.24 (d, J = 7.5Hz, 1H), 7.92-7.69 (m, 5H), 7.61-7.52 (m, 2H), 6.21-6.10 ( J = 15.3, 9.0 Hz, 1H), 3.84 (dd, J = 15.3, 1H), 5.15 (d, J = 14.4 Hz, , 0.9 Hz, 1H), 3.76-2.80 (m, 10H), 1.98-1.50 (m, 6H), 1.45 (t, J = 7.2 Hz, 3H).
[4534] Example 103 (6)
[4535] 4- (2-methoxybenzyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene hydrochloride
[4536]
[4537] TLC: Rf 0.49 (ethyl acetate: triethylamine = 6: 0.5);
[4538] _{NMR (DMSO-d 6):} δ 9.51 (brs, 2H), 8.21-8.11 (m, 1H), 7.89-7.75 (m, 3H), 7.74-7.58 (m, 4H), 7.51 (d, J = 7.5 1H), 7.07-7.38 (m, 1H), 7.08 (d, J = 8.1 Hz, 1H) (m, 1H), 4.52-4.37 (m, 1H), 4.31-4.12 (m, 2H), 3.95-3.82 (m, 2H), 3.81 (s, 3H).
[4539] Example 103 (7)
[4540] 4- (3-phenylpropyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene hydrochloride
[4541]
[4542] TLC; Rf 0.37 (ethyl acetate: triethylamine = 6: 0.5);
[4543] _{NMR (DMSO-d 6):} δ 9.50 (brs, 1H), 9.17 (brs, 1H), 8.16 (d, J = 6.3Hz, 1H), 7.90-7.73 (m, 5H), 7.68-7.58 (m, 2H), 7.35-7.16 (m, 5H), 6.44 (dd, J = 6.9,3.0Hz, 1H), 4.69-4.54 2H), 3.14-2.95 (m, 2H), 2.68 (t, J = 7.2 Hz, 2H), 2.09-1.91 (m, 2H).
[4544] Example 103 (8)
[4545] Dihydro-1,1-dioxide benzo [b] thiophene hydrochloride
[4546]
[4547] TLC; Rf 0.43 (ethyl acetate: triethylamine = 6: 0.5);
[4548] _{NMR (DMSO-d 6):} δ 9.94 (brs, 1H), 9.65 (brs, 1H), 8.17 (d, J = 6.9Hz, 1H), 7.90-7.75 (m, 3H), 7.75-7.67 (m, J = 2.1 Hz, 1H), 6.30 (t, J = 4.5 Hz, 1H), 4.72-7.58 (m, 2H) 2H), 3.75 (s, 6H), 4.57 (m, 1H), 4.43-4. 28 (m, 1H), 4.23 (brs, 2H), 4.00-3.67
[4549] Example 103 (9)
[4550] 4 - ((3R) -1-benzylpyrrolidin-3-yl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene dihydrochloride
[4551]
[4552] TLC: Rf 0.45 (methanol: ethyl acetate: triethylamine = 2: 8: 0.5);
[4553] _{NMR (CD 3 OD): δ} 8.20 (d, J = 6.9Hz, 1H), 7.91-7.70 (m, 5H), 7.66-7.54 (m, 4H), 7.53-7.43 (m, 3H), 6.18-6.05 (m, 1H), 4.77 (d, J = 14.1 Hz, 1H), 4.67-4.32 (m, 4H), 4.02-3.66 (m, 5H), 3.62-3.38 , 2H).
[4554] Example 103 (10)
[4555] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene dihydrochloride
[4556]
[4557] TLC: Rf 0.45 (methanol: ethyl acetate: triethylamine = 2: 8: 0.5);
[4558] _{NMR (CD 3 OD): δ} 8.20 (d, J = 6.9Hz, 1H), 7.91-7.70 (m, 5H), 7.66-7.54 (m, 4H), 7.53-7.43 (m, 3H), 6.18-6.04 (m, 1H), 4.78 (d, J = 12.9 Hz, 1H), 4.68-4.32 (m, 4H), 4.02-3.66 (m, 5H), 3.62-3.38 , 2H).
[4559] Example 103 (11)
[4560] Phenylthio) amino methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[4561]
[4562] Free body:
[4563] TLC: Rf 0.28 (ethyl acetate);
[4564] _{NMR (CDCl 3): δ 7.65-7.40} (m, 8H), 7.30-7.15 (m, 5H), 5.90 (dd, J = 9.3, 0.9Hz, 1H), 4.66 (d, J = 14.2Hz, 1H) , 3.92 (d, J = 14.2 Hz, 1H), 3.73 (dd, J = 15.0, 0.9 Hz, 1H), 3.42 (dd, J = 15.0, 9.3 Hz, 1H), 3.01-2.74 (m, 4H).
[4565] Hydrochloride:
[4566] TLC: Rf 0.28 (ethyl acetate);
[4567] _{NMR (DMSO-d 6):} δ 9.55 (br, 1H), 9.35 (br, 1H), 8.18 (dd, J = 6.2, 2.5Hz, 1H), 7.94-7.87 (m, 2H), 7.82-7.78 ( J = 7.5, 2.1 Hz, 1H), 4.69-4.65 (m, 2H), 7.29-7.25 (m, 3H) (m, 1H), 4.45-4.41 (m, 1H), 3.92 (dd, J = 15.3, 7.5 Hz, 1H), 3.84 (dd, J = 15.3, 2.1 Hz, 1H) ), 3.08-2.98 (m, 2H).
[4568] Example 103 (12)
[4569] Methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[4570]
[4571] Free body:
[4572] TLC: Rf 0.42 (hexane: AcOEt = 1: 2);
[4573] _{NMR (CDCl 3): δ 7.71} (dd, J = 7.2, 1.2Hz, 1H), 7.64-7.49 (m, 5H), 7.44-7.39 (m, 2H), 7.34-7.20 (m, 5H), 6.08 ( J = 15.0, 1.0 Hz, 1H), 4.66 (d, J = 14.1 Hz, 1H), 3.88 ), 3.61 (d, J = 12.9 Hz, 1H), 3.53 (d, J = 14.1 Hz, 1H), 3.47 (d, J = 12.9 Hz, 1H), 2.16 (s,
[4574] Hydrochloride:
[4575] TLC: Rf 0.42 (hexane: AcOEt = 1: 2);
[4576] NMR (CD ₃ OD + pyridine _{-d 5): δ 7.92 (d} , J = 7.5Hz, 1H), 7.73-7.63 (m, 5H), 7.56-7.50 (m, 2H), 7.37-7.31 (m, 5H) , 5.99 (dd, J = 7.0, 3.0 Hz, 1H), 4.52 (d, J = 14.4 Hz, 1H), 3.94-3.85 d, J = 13.0 Hz, 1H), 2.32 (s, 3H).
[4577] Example 103 (13)
[4578] Propyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[4579]
[4580] Free body:
[4581] TLC: Rf 0.27 (ethyl acetate: methanol: triethylamine = 8: 1: 1);
[4582] _{NMR (CDCl 3): δ 7.72} (dd, J = 7.5, 1.5Hz, 1H), 7.65-7.54 (m, 4H), 7.51 (dd, J = 7.5, 1.5Hz, 1H), 7.47-7.42 (m, 2H), 5.98 (t-form, J = 5.1 Hz, 1H), 4.56 (d, J = 13.8 Hz, 1H), 3.91-3.87 (m, 3H), 3.40-3.30 (m, 2H), 2.41-2.38 (m, 2H), 2.05-1.95 (m, 2H), 1.78-1.69 (m, 2H).
[4583] Hydrochloride:
[4584] TLC: Rf 0.27 (ethyl acetate: methanol: triethylamine = 8: 1: 1);
[4585] _{NMR (DMSO-d 6):} δ 9.32 (m, 1H), 9.08 (m, 1H), 8.14 (dd, J = 6.3, 2.1Hz, 1H), 7.90-7.78 (m, 5H), 7.67-7.62 ( (m, 2H), 6.40 (dd, J = 7.5, 2.0 Hz, 1H), 4.66-4.60 (m, 1H), 4.43-4.37 m, 4H), 3.03-2.97 (m, 2H), 2.26 (t, J = 8.0 Hz, 2H), 1.99-1.83 (m, 4H).
[4586] Example 103 (14)
[4587] 4-aminobenzyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[4588]
[4589] Free body:
[4590] TLC: Rf 0.47 (ethyl acetate: methanol: triethylamine = 8: 1: 1);
[4591] _{NMR (DMSO-d 6):} δ 7.90 (dd, J = 7.0, 2.0Hz, 1H), 7.80-7.61 (m, 7H), 6.97 (d, J = 8.5Hz, 2H), 6.52 (d, J = (Dd, J = 8.0, 1.8 Hz, 1H), 4.93 (s, 2H), 4.01 (d, J = 14.7 Hz, 1H), 3.91 1H), 3.84 (dd, J = 15.0, 1.8 Hz, 1H), 3.77 (d, J = 14.7 Hz, 1H), 3.48 (s, 2H).
[4592] Hydrochloride:
[4593] TLC: Rf 0.47 (ethyl acetate: methanol: triethylamine = 8: 1: 1);
[4594] _{NMR (DMSO-d 6):} δ 9.90 (br, 1H), 9.59 (br, 1H), 8.18 (dd, J = 7.0, 1.5Hz, 1H), 7.88-7.60 (m, 9H), 7.21 (d, 2H, J = 7.8 Hz, 2H), 6.37-6.34 (m, IH), 4.70-4.64 (m, IH), 4.42-4.32 .
[4595] Example 103 (15)
[4596] Yl) methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene- Thiophene
[4597]
[4598] Free body:
[4599] TLC: Rf 0.48 (ethyl acetate: methanol = 9: 1);
[4600] _{NMR (CDCl 3): δ 7.65-7.20} (m, 13H), 6.52 (d, J = 15.9Hz, 1H), 6.30 (dd, J = 9.3, 1.2Hz, 1H), 6.26 (dt, J = 15.9, J = 15.0, 1.2 Hz, 1H), 3.73 (dd, J = 15.0, 9.3 Hz, 1H), 3.42 (d, J = J = 14.3 Hz, 1H), 3.16 (d, J = 6.8 Hz, 2H), 2.60-2.40 (m, 8H).
[4601] Hydrochloride:
[4602] TLC: Rf 0.48 (ethyl acetate: methanol = 9: 1);
[4603] _{NMR (CD 3 OD + D 2} O): δ 7.93 (d, J = 7.0Hz, 1H), 7.78-7.72 (m, 4H), 7.66 (d, J = 7.0Hz, 1H), 7.61-7.50 (m J = 15.6 Hz, 1H), 6.33 (dt, J = 15.6, 7.7 Hz, 1H), 6.16 (d, J = 9.0 Hz, 1H), 7.41-7.33 , 4.45 (d, J = 14.5 Hz, 1H), 4.02 (dd, J = 15.0, 9.0 Hz, 1H) 1H), 3.85 (d, J = 14.5 Hz, 1H), 3.42 (br, 4H), 3.29 (br, 4H).
[4604] Example 103 (16)
[4605] Phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[4606]
[4607] Free body:
[4608] TLC: Rf 0.30 (ethyl acetate);
[4609] _{NMR (CDCl 3): δ 7.74} (d, J = 7.5Hz, 1H), 7.65-7.55 (m, 2H), 7.51-7.39 (m, 5H), 7.09 (dt, J = 7.5, 1.5Hz, 1H) , 6.97 (dd, J = 7.5, 1.5 Hz, 1H), 6.67 (dt, J = 7.5, 1.5 Hz, 1H) J = 14.3 Hz, 1H), 3.88 (d, J = 12.6 Hz, 1H), 3.82 (dd, J = 15.0 , 1.2 Hz, 1H), 3.81 (d, J = 12.6 Hz, 1H), 3.66 (dd, J = 15.0, 9.5 Hz, 1H).
[4610] Hydrochloride:
[4611] TLC: Rf 0.30 (ethyl acetate);
[4612] _{NMR (DMSO-d 6):} δ 8.17 (dd, J = 6.3, 2.4Hz, 1H), 7.87-7.71 (m, 5H), 7.66-7.61 (m, 2H), 7.50 (br, 2H), 7.29 ( (t, J = 7.5 Hz, 1H), 6.75 (d, J = 7.5, 1.2 Hz, 1H) (D, J = 13.8 Hz, 1H), 4.26-4.17 (m, 2H), 3.93-3.82 (d, (m, 2H).
[4613] Example 103 (17)
[4614] Methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[4615]
[4616] Free body:
[4617] TLC: Rf 0.50 (hexane: AcOEt = 1: 1);
[4618] _{NMR (CDCl 3): δ 7.66-7.56} (m, 4H), 7.53-7.51 (m, 2H), 7.48-7.43 (m, 2H), 7.30-7.25 (m, 2H), 7.21-7.11 (m, 3H J = 15.0 Hz, 1H), 6.36 (d, J = 9.3 Hz, 1H), 4.62 (d, J = J = 6.9 Hz, 2H), 2.55-2.50 (m, 1H), 2.05 (dt, J = (M, 2H), 1.35 (dt, J = 12.0, 3.5Hz, 1H), 1.85 (d, J = 11.5, 2.5Hz, 1H), 1.74-1.68 , &Lt; / RTI &gt; 1H), 1.16-1.02 (m, 1H).
[4619] Hydrochloride:
[4620] TLC: Rf 0.50 (hexane: AcOEt = 1: 1);
[4621] _{NMR (DMSO-d 6):} δ 10.42 (br, 1H), 8.22 (d, J = 7.0Hz, 1H), 7.92-7.72 (m, 5H), 7.65-7.60 (m, 2H), 7.31-7.15 ( J = 13.8, 5.3 Hz, 1H), 4.02 (dd, J), 6.30 (d, J = (D, J = 15.3 Hz, 1H), 3.42-3.39 (m, 1H), 3.12-3.00 (m, 3H), 2.60-2.42 1.49 (m, 5 H).
[4622] Example 103 (18)
[4623] 4-Chlorobenzyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[4624]
[4625] Free body:
[4626] TLC: Rf 0.43 (ethyl acetate);
[4627] _{NMR (CDCl 3): δ 7.75} (dd, J = 7.0, 1.2Hz, 1H), 7.66-7.51 (m, 5H), 7.47-7.42 (m, 2H), 7.32 (d, J = 8.4Hz, 2H) , 7.24 (d, J = 8.4 Hz, 2H), 5.81 (dd, J = 9.3, 1.3 Hz, 1H), 4.48 (d, J = 14.0 Hz, 1H) (Dd, J = 15.0, 1.3 Hz, 1H), 3.84 (d, J = 13.3 Hz, 1H) 1H).
[4628] Hydrochloride:
[4629] TLC: Rf 0.43 (ethyl acetate);
[4630] _{NMR (DMSO-d 6):} δ 9.86 (br, 1H), 9.55 (br, 1H), 8.16 (dd, J = 6.6, 1.8Hz, 1H), 7.88-7.72 (m, 5H), 7.67-7.62 ( 1H), 4.43-4.39 (m, 1H), 4.32 (d, J = 8.4 Hz, 2H) (s, 2H), 3.90 (dd, J = 15.5, 6.2 Hz, 1H), 3.84 (dd, J = 15.5, 3.5 Hz, 1H).
[4631] Example 103 (19)
[4632] Preparation of 4- (3-chlorobenzyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[4633]
[4634] Free body:
[4635] TLC: Rf 0.51 (ethyl acetate);
[4636] _{NMR (CDCl 3): δ 7.76} (dd, J = 7.0, 1.2Hz, 1H), 7.67-7.40 (m, 7H), 7.30-7.14 (m, 4H), 5.80 (dd, J = 9.2, 1.4Hz, J = 14.0 Hz, 1H), 3.48 (d, J = 14.0 Hz, 1H) 1H), 3.77 (d, J = 13.6 Hz, 1H), 3.69 (dd, J = 15.4, 9.2 Hz, 1H).
[4637] Hydrochloride:
[4638] TLC: Rf 0.51 (ethyl acetate);
[4639] _{NMR (DMSO-d 6):} δ 9.92 (br, 1H), 9.62 (br, 1H), 8.18 (dd, J = 6.6, 1.8Hz, 1H), 7.88-7.74 (m, 6H), 7.67-7.59 ( 1H), 4.44-4.40 (m, 1H), 4.35 (s, 3H), 7.52-7.45 (m, 2H), 6.39 (dd, J = 5.7,4.2Hz, 2H), 3.90 (dd, J = 15.6, 5.7 Hz, 1H), 3.84 (dd, J = 15.6, 4.2 Hz, 1H).
[4640] Example 103 (20)
[4641] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[4642]
[4643] Free body:
[4644] TLC: Rf 0.41 (ethyl acetate);
[4645] _{NMR (CDCl 3): δ 7.75} (dd, J = 7.2, 1.2Hz, 1H), 7.65-7.50 (m, 5H), 7.46-7.40 (m, 2H), 7.26-7.21 (m, 1H), 6.86- J = 14.1 Hz, 1H), 3.84 (d, J = 14.1 Hz, 1H), 6.79 (d, J = J = 13.0 Hz, 1H), 3.84 (dd, J = 15.0, 1.2 Hz, 1H), 3.80 1H).
[4646] Hydrochloride:
[4647] TLC: Rf 0.41 (ethyl acetate);
[4648] _{NMR (DMSO-d 6):} δ 9.83 (br, 1H), 9.55 (br, 1H), 8.16 (dd, J = 6.6, 1.8Hz, 1H), 7.89-7.78 (m, 3H), 7.73-7.61 ( J = 7.9 Hz, 1H), 7.15 (d, J = 7.9 Hz, 1H), 7.00 (dd, J = 7.9, J = 6.0, 3.9 Hz, 1H), 4.70-4.65 (m, IH), 4.42-4.37 (m, IH), 4.29 (br, 2H), 3.89 (dd, J = 15.5, 6.0 Hz, 1H), 3.84 (dd, J = 15.5, 3.9 Hz, 1H), 3.78 (s, 3H).
[4649] Example 103 (21)
[4650] Preparation of 4- (3,4-dichlorobenzyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[4651]
[4652] Free body:
[4653] TLC: Rf 0.42 (ethyl acetate);
[4654] NMR (CDCl ₃ ): 7.77 (dd, J = 7.2, 1.2 Hz, 1H), 7.67-7.52 (m, 5H), 7.47-7.39 J = 13.8 Hz, 1H), 5.76 (dd, J = 9.5, 1.2 Hz, 1H), 4.45 1H), 3.84 (dd, J = 13.8 Hz, 1H), 3.78 (d, J = 13.8 Hz, 1H), 3.70 (dd, J = 15.0, 9.5 Hz, 1H).
[4655] Hydrochloride:
[4656] TLC: Rf 0.42 (ethyl acetate);
[4657] _{NMR (DMSO-d 6):} δ 9.94 (br, 1H), 9.62 (br, 1H), 8.17 (dd, J = 6.6, 2.1Hz, 1H), 7.96 (d, J = 1.8Hz, 1H), 7.89 (D, J = 5.5, 4.2 Hz, 1H), 4.75-4.68 (m, 1H), 4.45-4.40 (m, 1H), 4.35 (s, 2H), 3.95 (dd, J = 15.5, 5.5 Hz, 1H), 3.85 (dd, J = 15.5, 4.2 Hz, 1H).
[4658] Example 103 (22)
[4659] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[4660]
[4661] Free body:
[4662] TLC: Rf 0.43 (ethyl acetate);
[4663] _{NMR (CDCl 3): δ 7.73} (dd, J = 7.5, 1.2Hz, 1H), 7.65-7.49 (m, 5H), 7.46-7.41 (m, 2H), 6.77 (d, J = 1.5Hz, 1H) , 6.74 (d, J = 8.0 Hz, 1H), 6.69 (dd, J = 8.0, 1.5 Hz, 1H), 5.95-5.94 (m, 2H), 5.88 J = 15.0 Hz, 1H), 3.77 (d, J = 13.0 Hz, 1H), 3.86 (dd, J = 3.68 (d, J = 13.0 Hz, 1H), 3.68 (dd, J = 15.0, 9.5 Hz, 1H).
[4664] Hydrochloride:
[4665] TLC: Rf 0.43 (ethyl acetate);
[4666] _{NMR (DMSO-d 6):} δ 9.78 (br, 1H), 9.47 (br, 1H), 8.15 (dd, J = 6.6, 1.8Hz, 1H), 7.88-7.72 (m, 5H), 7.66-7.61 ( J = 7.8 Hz, 1H), 6.30 (t-form, J = 7.8 Hz, 1H), 7.05 (d, J = = 4.5 Hz, IH), 6.05 (s, 2H), 4.67-4.61 (m, IH), 4.38-4.33 (m, IH), 4.23 (s, 2H), 3.93-3.83 (m, 2H).
[4667] Example 103 (23)
[4668] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[4669]
[4670] Free body:
[4671] TLC: Rf 0.36 (ethyl acetate);
[4672] _{NMR (CDCl 3): δ 7.71} (dd, J = 7.0, 1.3Hz, 1H), 7.63-7.48 (m, 5H), 7.45-7.39 (m, 2H), 7.00 (t, J = 7.8Hz, 1H) , 6.84 (dd, J = 7.8,1.5Hz, 1H), 6.78 (dd, J = 7.8,1.5Hz, 1H), 6.06 (D, J = 15.3 Hz, 1H), 3.92 (d, J = 14.1 Hz, 1H), 3.86 3.76 (s, 3H), 3.73 (dd, J = 15.0, 9.3 Hz, 1H), 3.69 (d, J = 13.3 Hz, 1H).
[4673] Hydrochloride:
[4674] TLC: Rf 0.36 (ethyl acetate);
[4675] _{NMR (DMSO-d 6):} δ 9.70-9.60 (br, 2H), 8.17 (dd, J = 6.6, 2.1Hz, 1H), 7.89-7.73 (m, 5H), 7.67-7.62 (m, 2H), 1H), 7.15-7.13 (m, 2H), 6.12 (dd, J = 6.8,2.5Hz, 1H), 4.71-4.67 2H), 3.83 (s, 3H), 3.80 (s, 3H).
[4676] Example 103 (24)
[4677] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[4678]
[4679] Free body:
[4680] TLC: Rf 0.20 (ethyl acetate);
[4681] _{NMR (CDCl 3): δ 7.79} (dd, J = 7.2, 1.2Hz, 1H), 7.66-7.52 (m, 5H), 7.47-7.42 (m, 2H), 6.54 (s, 2H), 5.72 (dd, (D, J = 14.0 Hz, 1H), 3.86 (s, 3H), 3.84 (s, 3H), 3.84 J = 15.0, 1.2 Hz, 1H), 3.82 (d, J = 13.5 Hz, 1H), 3.74 (d, J = 13.5 Hz, 1H), 3.66 (dd, J = 15.0, 9.3 Hz, 1H).
[4682] Hydrochloride:
[4683] TLC: Rf 0.20 (ethyl acetate);
[4684] _{NMR (DMSO-d 6):} δ 9.98 (br, 1H), 9.63 (br, 1H), 8.18 (dd, J = 6.6, 1.5Hz, 1H), 7.89-7.78 (m, 3H), 7.72-7.60 ( 2H), 6.30 (dd, J = 6.0, 3.5 Hz, 1H), 4.69-4.66 (m, , 3.92-3.84 (m, 2H), 3.80 (s, 6H), 3.67 (s, 3H).
[4685] Example 103 (25)
[4686] Yl) methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[4687]
[4688] Free body:
[4689] TLC: Rf 0.49 (hexane: AcOEt = 1: 2);
[4690] _{NMR (CDCl 3): δ 7.66-7.52} (m, 6H), 7.48-7.43 (m, 2H), 6.18 (dd, J = 9.0, 1.0Hz, 1H), 4.69 (d, J = 14.3Hz, 1H) (Dd, J = 15.0, 1.0 Hz, 1H), 3.72 (dd, J = 15.0, 9.0 Hz, 1H), 3.49-3.35 (m, 4H) 2.52-2.45 (m, 2H), 2.36-2.29 (m, 2H), 1.46 (s, 9H).
[4691] Hydrochloride:
[4692] TLC: Rf 0.49 (hexane: AcOEt = 1: 2);
[4693] _{NMR (CD 3 OD): δ} 8.11 (d, J = 7.2Hz, 1H), 7.92-7.83 (m, 2H), 7.77-7.73 (m, 3H), 7.60-7.55 (m, 2H), 6.03 (dd (D, J = 14.3 Hz, 1H), 4.71 (d, J = 14.3 Hz, 1H), 4.22 (br, 2H), 3.99 8.7 Hz, 1H), 3.84 (dd, J = 15.3, 1.0 Hz, 1H), 3.65-3.25 (br, 6H), 1.47 (s, 9H).
[4694] Example 103 (26)
[4695] Dihydro-1, 1-dioxide benzo [b] thiophene dihydrochloride (2-diisopropylaminoethyl) aminomethyl-3-phenylsulfonyl-
[4696]
[4697] TLC: Rf 0.43 (methanol: ethyl acetate: triethylamine = 2: 8: 0.5);
[4698] _{NMR (CD 3 OD + D 2} O): δ 8.18 (d, J = 7.5Hz, 1H), 7.97-7.76 (m, 5H), 7.70-7.60 (m, 2H), 6.20-6.12 (m, 1H) , 4.85 (d, J = 13.8 Hz, 1H), 4.67 (d, J = 13.8 Hz, 1H), 4.01-3.50 (m, 8H), 1.44 (d, J = 6.3 Hz, 12H).
[4699] Example 103 (27)
[4700] 4-yl) ethyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene dihydrochloride
[4701]
[4702] TLC: Rf 0.37 (methanol: ethyl acetate: triethylamine = 2: 8: 0.5);
[4703] _{NMR (CD 3 OD + D 2} O): δ 8.18 (d, J = 7.5Hz, 1H), 7.97-7.76 (m, 5H), 7.69-7.60 (m, 2H), 6.17-6.10 (m, 1H) (M, 2H), 4.86 (d, J = 13.8 Hz, 1H), 4.69 ), 3.51-3.33 (m, 4H).
[4704] Example 103 (28)
[4705] N-propyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[4706]
[4707] Free body:
[4708] TLC: Rf 0.51 (ethyl acetate: triethylamine = 9: 1);
[4709] _{NMR (CDCl 3): δ 7.68} (d, J = 7.2Hz, 1H), 7.64-7.46 (m, 5H), 7.44-7.39 (m, 2H), 6.29 (dd, J = 9.3, 1.2Hz, 1H) (Dd, J = 15.0, 1.2 Hz, 1H), 3.72 (dd, J = 15.0, 9.3 Hz, 1H), 3.58 (d, J = 14.4 Hz, 1H) 1H), 2.70-2.30 (m, 10H), 1.57-1.38 (m, 8H), 0.79 (t, J = 7.2 Hz, 3H).
[4710] Hydrochloride:
[4711] TLC: Rf 0.51 (ethyl acetate: triethylamine = 9: 1);
[4712] NMR (CD ₃ OD + pyridine-d ₅ ): 隆 7.93 (d, J = 7.2 Hz, 1H), 7.74-7.68 (m, 4H), 7.61-7.52 (Dd, J = 15.3, 1.2 Hz, 1H), 3.85 (d, J = 4H), 2.97-2.81 (m, 2H), 2.61-2.45 (m, 2H), 1.85-1.77 (m, 4H) , 1.65-1.53 (m, 4H), 0.89 (t, J = 7.3 Hz, 3H).
[4713] Example 103 (29)
[4714] 3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene (4-fluoro-
[4715]
[4716] Free body:
[4717] TLC: Rf 0.48 (ethyl acetate: triethylamine = 9: 1);
[4718] _{NMR (CDCl 3): δ 7.77} (d, J = 7.2Hz, 1H), 7.65-7.47 (m, 5H), 7.45-7.40 (m, 2H), 6.09 (d, J = 9.0, 1.0Hz, 1H) (Dd, J = 15.0, 1.0 Hz, 1H), 4.54 (d, J = 15.0 Hz, 1H), 3.88 2H), 2.38-2.17 (m, 6H), 1.55-1.48 (m, 4H), 1.42-1. 35 (m, 2H), 2.84 (m, , 1.06 (d, J = 6.6 Hz, 3H), 1.03 (d, J = 6.6 Hz, 3H).
[4719] Hydrochloride:
[4720] TLC: Rf 0.48 (ethyl acetate: triethylamine = 9: 1);
[4721] NMR (CD ₃ OD + pyridine _{-d 5): δ 7.99 (d} , J = 7.5Hz, 1H), 7.75-7.70 (m, 4H), 7.61-7.54 (m, 3H), 5.93 (dd, J = 8.7, J = 15.6 Hz, 1H), 3.88 (dd, J = 15.6 Hz, 1H), 3.99 (dd, J = 15.3, 1.5 Hz, 1H), 3.20-2.80 (m, 9H), 1.82-1.75 (m, 4H), 1.63-1.58 (m, 2H), 1.17-1.14 (m, 6H).
[4722] Example 103 (30)
[4723] 4-Dimethoxybenzyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[4724]
[4725] Free body:
[4726] TLC: Rf 0.19 (ethyl acetate);
[4727] _{NMR (CDCl 3): δ 7.76} (dd, J = 7.2, 1.0Hz, 1H), 7.65-7.51 (m, 5H), 7.46-7.41 (m, 2H), 6.84-6.82 (m, 3H), 5.79 ( J = 14.0 Hz, 1H), 3.87 (s, 6H), 3.85 (d, J = 15.0 Hz, 1H) 1H), 3.82 (d, J = 13.2 Hz, 1H), 3.73 (d, J = 13.2 Hz, 1H), 3.66 (dd, J = 15.0, 9.3 Hz, 1H).
[4728] Hydrochloride:
[4729] TLC: Rf 0.19 (ethyl acetate);
[4730] _{NMR (DMSO-d 6):} δ 10.00-9.70 (br, 2H), 8.38-8.28 (m, 1H), 8.06-7.94 (m, 3H), 7.88-7.76 (m, 4H), 7.56 (d, J J = 8.4 Hz, 1H), 6.43-6.38 (m, 1H), 4.80 (d, J = 12.8 Hz, , 4.53 (d, J = 12.8 Hz, 1H), 4.40 (s, 2H), 4.13-4.00 (m, 2H), 3.94 (s, 6H).
[4731] Example 103 (31)
[4732] Propyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene dihydrochloride
[4733]
[4734] TLC; Rf 0.33 (ethyl acetate: methanol: triethylamine = 8: 2: 0.5);
[4735] _{NMR (CD 3 OD): δ} 8.18 (d, J = 7.2Hz, 1H), 7.92-7.73 (m, 5H), 7.67-7.57 (m, 2H), 6.22-6.23 (m, 1H), 4.80 (d 1H, J = 13.5 Hz, 1H), 4.62 (d, J = 13.5 Hz, 1H), 3.98-3.91 (m, 1H), 3.83-3.74 2.17 (m, 2H), 2.07 - 1.52 (m, 6H), 1.41 (d, J = 6.3 Hz, 3H).
[4736] Example 103 (32)
[4737] Yl) methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene 2 Hydrochloride
[4738]
[4739] TLC; Rf 0.41 (ethyl acetate: methanol: triethylamine = 8: 2: 0.5);
[4740] _{NMR (D 2 O): δ} 8.17-8.08 (m, 1H), 8.03-7.94 (m, 2H), 7.91-7.82 (m, 1H), 7.79-7.73 (m, 2H), 7.72-7.62 (m, 2H), 4.71 (d, J = 14.4 Hz, 1H), 4.65 (d, J = 14.4 Hz, 1H), 4.21-4.05 (m, 2H), 3.87-3.75 , 4H), 3.38-2.98 (m, 4H), 2.52-2.32 (m, 2H), 2.19-1.93 (m, 4H), 1.91-1.65 (m, 3H), 1.59-1.
[4741] Example 103 (33)
[4742] Propyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene dihydrochloride
[4743]
[4744] TLC: Rf 0.25 (methanol: ethyl acetate: triethylamine = 2: 8: 0.5);
[4745] _{NMR (CD 3 OD + D 2} O): δ 8.16 (d, J = 7.2Hz, 1H), 7.95-7.74 (m, 5H), 7.69-7.59 (m, 2H), 6.17-6.08 (m, 1H) , 4.78 (d, J = 14.1 Hz, 1H), 4.62 (d, J = 14.1 Hz, 1H), 4.02-3.88 (m, 1H), 3.85-3.73 ), 2.3 8-2.21 (m, 2H), 2.14-1.44 (m, 6H).
[4746] Example 103 (34)
[4747] 4- (3-bromobenzyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene hydrochloride
[4748]
[4749] TLC: Rf 0.50 (ethyl acetate: triethylamine = 6: 0.5);
[4750] _{NMR (DMSO-d 6):} δ 9.83 (brs, 1H), 9.56 (brs, 1H), 8.16 (d, J = 6.6Hz, 1H), 7.90-7.70 (m, 6H), 7.68-7.58 (m, 4H), 7.41 (t, J = 7.5 Hz, 1H), 6.41-6.28 (m, IH), 4.80-4.60 (m, IH), 4.52-4.22 (m, 3H), 3.96-3.80 .
[4751] Example 103 (35)
[4752] 4- (4-nitrobenzyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene hydrochloride
[4753]
[4754] TLC: Rf 0.34 (ethyl acetate: triethylamine = 6: 0.5);
[4755] _{NMR (DMSO-d 6):} δ 10.05 (brs, 1H), 9.79 (brs, 1H), 8.29 (d, J = 8.1Hz, 2H), 8.18 (d, J = 6.6Hz, 1H), 7.94-7.70 (m, 7H), 7.67-7.57 (m, 2H), 6.48-6.33 (m, 1H), 4.83-4.64 .
[4756] Example 103 (36)
[4757] 4-aminosulfonylbenzyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[4758]
[4759] Free body:
[4760] TLC: Rf 0.40 (ethyl acetate: methanol = 9: 1);
[4761] _{NMR (DMSO-d 6):} δ 7.93 (dd, J = 7.0, 1.5Hz, 1H), 7.79-7.66 (m, 7H), 7.63-7.58 (m, 2H), 7.53 (d, J = 8.0Hz, J = 15.0, 8.3 Hz, 1H), 7.31 (s, 2H), 5.93 (dd, J = 8.3, 1.5 Hz, 1H) 3.87 (dd, J = 15.0,1.5 Hz, 1H), 3.82 (d, J = 14.1 Hz, 1H), 3.75 (s, 2H), 2.86 (br, 1H).
[4762] Hydrochloride:
[4763] TLC: Rf 0.40 (ethyl acetate: methanol = 9: 1);
[4764] _{NMR (DMSO-d 6):} δ 9.80 (br, 1H), 9.52 (br, 1H), 8.15 (d, J = 7.0Hz, 1H), 7.89-7.74 (m, 9H), 7.67-7.62 (m, 2H), 7.44 (s, 2H), 6.37-6.32 (m, IH), 4.78-4.70 (m, IH), 4.47-4.41 2H).
[4765] Example 103 (37)
[4766] 4-Piperazin-1-yl) methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene dihydrochloride
[4767]
[4768] TLC: Rf 0.10 (ethyl acetate: methanol: triethylamine = 8: 2: 1);
[4769] _{NMR (CD 3 OD + D 2} O): δ 7.96 (d, J = 7.8Hz, 1H), 7.80-7.67 (m, 5H), 7.61-7.56 (m, 2H), 6.16 (dd, J = 9.0, J = 14.5 Hz, 1H), 3.89 (dd, J = 14.5 Hz, 1H) 15.4, 1.3 Hz, 1 H), 3.37-3.33 (m, 4H), 2.98-2.90 (m, 4H).
[4770] Example 103 (38)
[4771] Methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[4772]
[4773] Free body:
[4774] TLC: Rf 0.38 (ethyl acetate: methanol = 9: 1);
[4775] NMR (CDCl ₃ ): 隆 7.69 (dd, J = 7.0, 1.5 Hz, 1H), 7.64-7.49 (m, 5H), 7.45-7.40 J = 14.3 Hz, 1H), 3.85 (dd, J = 15.0, 1.0 Hz, 1H), 3.81 (d, J = (d, J = 15.0, 9.0 Hz, 1H), 3.75 (s, 3H), 3.75 (s, 6H), 3.73 (d, J = 12.6 Hz, 1H)
[4776] Hydrochloride:
[4777] TLC: Rf 0.38 (ethyl acetate: methanol = 9: 1);
[4778] _{NMR (DMSO-d 6):} δ 9.11 (br, 1H), 8.94 (br, 1H), 8.16-8.13 (m, 1H), 7.88-7.87 (m, 2H), 7.84-7.79 (m, 1H), 1H), 4.39-4.34 (m, 1H), 4.18-7.61 (m, 4H), 6.31 (s, 2H), 5.92 (dd, J = 4 . (D, J = 15.3, 8.0 Hz, 1H), 3.83 (dd, J = 15.3, 1.8 Hz, 1H), 3.82 (s, 3H) , &Lt; / RTI &gt; 3.79 (s, 6H).
[4779] Example 103 (39)
[4780] 4-Piperidin-1-yl) carbonylmethylaminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[4781]
[4782] Free body:
[4783] TLC: Rf 0.42 (ethyl acetate: methanol: triethylamine = 8: 1: 1);
[4784] _{NMR (CDCl 3): δ 7.75} (dd, J = 6.9, 2.1Hz, 1H), 7.66-7.60 (m, 3H), 7.58-7.53 (m, 2H), 7.48-7.43 (m, 2H), 6.13 ( (dd, J = 9.0, 1.2 Hz, 1H), 4.61 (d, J = 13.8 Hz, 1H), 3.97 J = 16.0 Hz, 1H), 3.50 (d, J = 15.0, 9.0 Hz, 1H) , 3.30 (t, J = 5.2 Hz, 2H), 1.69 - 1.55 (m, 6H).
[4785] Hydrochloride:
[4786] TLC: Rf 0.42 (ethyl acetate: methanol: triethylamine = 8: 1: 1);
[4787] _{NMR (DMSO-d 6):} δ 9.63 (br, 1H), 9.18 (br, 1H), 8.11 (d, J = 7.2Hz, 1H), 7.93-7.80 (m, 5H), 7.70-7.64 (m, 2H), 6.28 (dd, J = 6.0, 4.0 Hz, 1H), 4.83 (d, J = 13.2 Hz, 1H), 4.32 (d, J = 13.2 Hz, 1H), 4.28-4.16 (Dd, J = 15.3, 6.0 Hz, 1H), 3.80 (dd, J = 15.3, 4.0 Hz, 1H), 3.54-3.50 (m, 2H), 3.37-3.32 m, 6H).
[4788] Example 103 (40)
[4789] 4-Pyrrolidin-1-yl) ethylaminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene dihydrochloride
[4790]
[4791] TLC: Rf 0.22 (methanol: ethyl acetate: triethylamine = 2: 8: 0.5);
[4792] _{NMR (CD 3 OD + D 2} O): δ 8.16 (d, J = 7.5Hz, 1H), 7.94-7.75 (m, 5H), 7.68-7.58 (m, 2H), 6.15-6.08 (m, 1H) , 4.81 (d, J = 13.8 Hz, 1H), 4.63 (d, J = 13.8 Hz, 1H), 4.01-3.88 (m, 1H), 3.86-3.76 ), 3.6-3.38 (m, 4H), 2.20-2.06 (m, 4H).
[4793] Example 103 (41)
[4794] Yl) methyl-1, 1-dioxo [b] thiophene dihydrochloride (4-fluoro-
[4795]
[4796] TLC: Rf 0.51 (ethyl acetate: triethylamine = 6: 0.5);
[4797] _{NMR (CD 3 OD + D 2} O): δ 7.90 (d, J = 7.5Hz, 1H), 7.79-7.52 (m, 7H), 7.04-6.96 (m, 2H), 6.95-6.87 (m, 1H) , 4.25 (s, 2H), 4.01 (dd, J = 15.6, 8.7 Hz, 1H), 6.01 (s, 2H), 4.45 (d, 3.90 (dd, J = 15.6, 1.2 Hz, 1H), 3.77 (d, J = 14.4 Hz, 1H), 3.50-3.10 (br, 4H), 2.98-2.63 (br, 4H).
[4798] Example 104
[4799] 4-cyano-6,7-dihydrobenzo [b] thiophene
[4800]
[4801] 4-keto-4,5,6,7-tetrahydrothianaphthene (20 g) and trimethylsilyl anion (18 ml) were successively added to a suspension of zinc iodide (200 g) in acetonitrile (200 ml) Lt; / RTI &gt; for 5 hours. The reaction mixture was concentrated. The residue was dissolved in pyridine (65 ml), phosphorus oxychloride (15 ml) was added dropwise at room temperature, and the mixture was refluxed for 30 minutes. The reaction mixture was ice-cooled and isopropanol was added dropwise. The reaction mixture was added to ice water and extracted with ethyl acetate. The extract was washed successively with hydrochloric acid, water and saturated brine, dried over anhydrous magnesium sulfate and concentrated to obtain the title compound (17 g) having the following physical data.
[4802] TLC: Rf 0.45 (hexane: AcOEt = 3: 1);
[4803] _{NMR (CDCl 3): δ 7.12} (d, J = 5.4Hz, 1H), 7.07 (d, J = 5.4Hz, 1H), 6.62 (t, J = 4.8Hz, 1H), 2.93 (t, J = 9.0 Hz, 2H), 2.60 (td, J = 9.0, 4.8 Hz, 2H).
[4804] Example 105
[4805] 4-cyanobenzo [b] thiophene
[4806]
[4807] The compound (17 g) prepared in Example 104 was dissolved in benzene (200 ml), and 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (30 g) was added. The mixture was refluxed for 1 hour and then filtered. The filtrate was concentrated and extracted with a mixed solvent (hexane: ethyl acetate = 1: 1). The extract was washed successively with an aqueous solution of sodium hydroxide, water and saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was purified by silica gel column chromatography (hexane: ethyl acetate = 100: 1) to obtain the title compound (14.5 g) having the following physical data.
[4808] TLC: Rf 0.40 (hexane: AcOEt = 4: 1);
[4809] _{NMR (CDCl 3): δ 7.45} (t, J = 7.5Hz, 1H), 7.60 (d, J = 5.0Hz, 1H), 7.70 (d, J = 5.0Hz, 1H), 7.75 (d, J = 7.5 Hz, 1 H), 8.10 (d, J = 7.5 Hz, 1 H).
[4810] Example 106
[4811] 4-Carboxybenzo [b] thiophene
[4812]
[4813] 1) 85% Potassium hydroxide (19 g) was added to an ethylene glycol (50 ml) suspension of the compound (14.5 g) prepared in Example 105 and the mixture was stirred at 180 캜 for 2 hours. The reaction mixture was poured into hydrochloric acid to acidify and extracted with ethyl acetate. The extract was washed successively with water and saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was recrystallized from a mixed solvent of ethyl acetate and hexane to obtain the title compound (12.2 g) having the following physical data.
[4814] The title compound can also be prepared by the following method.
[4815] 2) A mixture of the compound prepared in Example 104 (1.61 g), nitrobenzene (2.46 g), ethylene glycol (10 ml) and 10% palladium carbon (161 mg) was heated at 200 ° C for 3 hours, at 180 ° C for 17 hours Lt; / RTI &gt; 85% potassium hydroxide (1.98 g) was added at 150 占 폚, and the mixture was stirred at 180 占 폚 for 1 hour. The reaction mixture was cooled to room temperature, water (10 ml) and activated charcoal were added and then filtered. The filtrate was washed with ethyl acetate (20 ml), concentrated hydrochloric acid (2.5 ml) was added to the aqueous layer, extracted with ethyl acetate, washed successively with water and saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was recrystallized from acetonitrile (25 ml) to give the title compound (1.46 g).
[4816] TLC: Rf 0.10 (hexane: AcOEt = 4: 1);
[4817] _{NMR (CDCl 3): δ 8.32} (dd, J = 5.6, 1.0Hz, 1H), 8.27 (dd, J = 7.6, 1.0Hz, 1H), 8.18-8.11 (m, 1H), 7.68 (d, J = 5.6 Hz, 1 H), 7.51-7.41 (m, 1 H).
[4818] Example 107
[4819] 4-carboxy-1, 1-dioxo [b] thiophene
[4820]
[4821] The compound (35 g) prepared in Example 106 was suspended in methanol (720 ml), and then oxone (362 g) of pure water (720 ml) was added at room temperature, followed by stirring at 40 ° C for 2 hours. The reaction mixture was filtered and the filtrate was concentrated. The residue was extracted with ethyl acetate. The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate, and concentrated under reduced pressure. The residue was crystallized from hexane and then dried to obtain the inventive compound (30 g) having the following physical properties.
[4822] TLC: Rf 0.18 (ethyl acetate);
[4823] _{NMR (CDCl 3): δ 8.28} (d, J = 7.5Hz, 1H), 8.26 (d, J = 7.5Hz, 1H), 7.94 (d, J = 7.5Hz, 1H), 7.66 (t, J = 7.5 Hz, 1 H), 6.87 (d, J = 7.5 Hz, 1 H).
[4824] A separate preparation example of the compound of the present invention
[4825] The compounds prepared in Examples 35 (49) to (61), Example 70, Example 94, and Examples 103 to 103 (29) were prepared in the same manner as in Example 108 or Example 109 shown below Can also be produced.
[4826] 1) For example, the compound shown in Example 35 (50) can be also prepared by the following method.
[4827] Example 108
[4828] 4-Pyridin-3-ylmethyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene dihydrochloride
[4829]
[4830] A solution of 3- (aminomethyl) pyridine (73 μl) in dimethylformamide (1 ml) was added to a solution of the compound prepared in Example 82 in dimethylformamide (5 ml) under an argon atmosphere and 5% palladium- 50 mg) was further added thereto, followed by hydrogen substitution, followed by stirring at room temperature for 1.5 hours. The reaction mixture was filtered and concentrated, and the obtained residue was purified by silica gel column chromatography (chloroform: methanol = 25: 1) to give 231 mg of 4N hydrogen chloride / ethyl acetate as a hydrochloride, The compound of the present invention was obtained by recrystallization.
[4831] The free form of the compound represented by the formula (52) can also be produced by the following method.
[4832] Example 109
[4833] Methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
[4834]
[4835] (53 μl), sodium cyanoborohydride (63 mg), concentrated hydrochloric acid (2 drops), and methanol (0.5 ml) were added to a dichloromethane (2 ml) suspension of the compound (168 mg) And the mixture was stirred at room temperature for 6 hours. Water was added to the reaction mixture and extracted with a mixed solvent (methylene chloride and methanol). The organic layer was washed with saturated brine, dried over anhydrous magnesium sulfate and concentrated. The residue was purified by silica gel column chromatography to obtain the compound (50 mg) of the present invention.
[4836] 2) The compound prepared in Example 81 (1) was synthesized in the same manner as in Example 27 using the compound prepared in Example 107 instead of 5-methyl-1,1-dioxide benzo [b] thiophene And further converting it into a corresponding free form by a known method if necessary.
[4837] 3) The compounds prepared in Examples 35 to 35 (32), Example 45 (1) to 45 (2), Example 70, Example 71 and Example 87 were treated in the same manner as in Example 100 Can also be produced.
[4838] For example, the compound prepared in Example 35 (11) can be used in place of the free or sodium salt of the compound prepared in Example 81 (1) and 2- (piperidin-1-yl) Ethylamine in the same manner as in the method described in Example 100.
[4839] Formulation example
[4840] Formulation Example 1
[4841] The following ingredients were mixed by a conventional method and then tableted to obtain 100 tablets containing 50 mg of the active ingredient per tablet.
[4842] · 4- (Pyridin-3-ylmethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene ... 5.0 g
[4843] · Carboxymethylcellulose calcium (disintegrating agent) ... ... 0.2 g
[4844] · Magnesium stearate (lubricant) ... ... 0.1 g
[4845] · Microcrystalline cellulose ... ... 4.7 g
[4846] Formulation Example 2
[4847] The following components were mixed by a conventional method, and the solution was sterilized by a conventional method. The solution was filled into ampoules in an amount of 5 ml each and lyophilized by a conventional method to obtain a solution containing 20 mg of active ingredient We got 100 ampoules.
[4848] · 4- (Pyridin-3-ylmethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene ... 2.0 g
[4849] · Mannitol ... ... 20 g
[4850] ·Distilled water… ... 500 ml

权利要求:
Claims (16)
[1" claim-type="Currently amended] 6 and / or an interleukin-12 production inhibitor containing a condensed thiophene derivative represented by the following formula (I), an N-oxide derivative thereof or a non-toxic salt thereof as an active ingredient.
Formula I

[In the formula, Represents a single bond or a double bond,
Y is or
(ii) a hydrogen atom (provided that
Represents a double bond, Y represents a hydrogen atom,
Is a single bond, Y is , &Lt; / RTI &gt;
m and n each independently represent 0 or an integer of 1 to 2,
p represents 0 or an integer of 1 to 4,
q represents 0 or an integer of 1 to 5,
Z represents a single bond, a C _1-8 alkylene group, a C _2-8 alkenylene group or a C _2-8 alkynylene group,
silver
(i) a benzene ring or
(ii) a 6-membered monocyclic heterocyclic aryl containing 1 to 2 nitrogen atoms,
silver
(i) a monocyclic C of _{3 to 15,} bicyclic, tricyclic carbon ring or triple
(ii) a single, double or triple cyclic heterocycle of 4 to 18 members including 1 to 4 nitrogen atoms, 1 to 2 oxygen atoms and / or 1 sulfur atom,
p &lt; RTI ID = 0.0 &gt; Ri &lt; / RTI &^gt;
(i) a C _1-8 alkyl group,
(ii) a C _2-8 alkenyl group,
(iii) a C _2-8 alkynyl group,
(iv) a nitro group,
(v) a cyano group,
(vi) a halogen atom,
(vii) Cyc ¹ group,
(viii) a C _1-8 alkyl group, a C _2-8 alkenyl group or a C _2-8 alkynyl group substituted by a halogen atom or a Cyc ¹ group, or
(ix) -A ¹ -A ² -A ³ ,
A ¹ is
(i) single bond,
(ii) a C _1-8 alkylene group,
(iii) a C _2-8 alkenylene group or
(iv) a C _2-8 alkynylene group,
A ² is
(i) -O- group,
(ii) -NR ³ - group,
(iii) -C (O) - group,
(iv) -CH (OH) - group,
(v) -C (O) NR 4 - group,
(vi) -NR &lt; ⁵ &gt; C (O)
(vii) -C (O) O- group,
(viii) -OC (O) - group,
(ix) -SO ₂ NR ⁶ - group,
(x) -NR ⁷ SO ₂ - group,
(xi) -C (O) NR &lt; ⁹ &gt; O- group,
(xii) -OC (O) NR &lt; ¹⁰ &gt; - group,
(xiii) -NR ¹¹ C (O) NR ¹² - group,
(xiv) -NR &lt; ¹³ &gt; C (O) O- group or
(xv) -OC (O) O- group,
[Wherein R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁹ , R ¹⁰ , R ¹¹ , R ¹² and R ¹³ each independently represent a hydrogen atom, a C _1-8 alkyl group, ¹ group, a -OR ¹⁴ group (in which R ¹⁴ represents a hydrogen atom or a C _1-8 alkyl group) or a C _1-8 alkyl group substituted with a cyano group, and each group represented by A ² represents a The combined hand is coupled to A ³ ),
A ³ is
(i) a hydrogen atom,
(ii) a C _1-8 alkyl group,
(iii) a C _2-8 alkenyl group,
(iv) a C _2-8 alkynyl group,
(v) Cyc group ¹ or
(vi) a C _1-8 alkyl group, a C _2-8 alkenyl group or a C _2-8 alkynyl group substituted with 1 to 3 groups selected from the following (a) to (i)
(a) a halogen atom,
(b) a cyano group,
(c) -P (O) (R ¹⁵ ) ₂ group,
^{(d) -Si (R 16)} 3 group,
(e) Cyc ¹ group,
(f) -C (O) R &lt; ¹⁷ &gt; groups,
(g) -OR ¹⁸ groups,
(h) -NR ¹⁹ R ²⁰ group,
(i) -SR ²¹ group;
There is a plurality of R ¹⁵ each independently represents a hydroxyl group or C _1~8 alkoxy,
The plural R &lt; ¹⁶ &gt; s each independently represent a C _1-8 alkyl group,
R ¹⁷ is
(i) a hydrogen atom,
(ii) a C _1-8 alkyl group,
(iii) a hydroxyl group,
(iv) a C _1-8 alkoxy group,
(v) Cyc group ¹ or
(vi) -NR ²² R ²³ group (wherein R ²² represents a hydrogen atom, a C _1-8 alkyl group, a phenyl group or a C _1-8 alkyl group substituted with a phenyl group, and R ²³ represents a hydrogen atom, a C _1-8 alkyl group , Cyc substituted with ¹ group Cyc ¹ or a group or an NR ²⁴ R ²⁵ group (R ²⁴ and R ²⁵ represents a C _1~8 alkyl group substituted by a hydrogen atom, C _1~8 alkyl group, a phenyl group, a phenyl group, each independently) A C _1-8 alkyl group)
R ¹⁸ is
(i) a hydrogen atom,
(ii) a C _1-8 alkyl group,
(iii) a C _2-8 alkenyl group,
(iv) Cyc ¹ or a group
(v) a Cyc ¹ group, a Si (R ²⁶ ) ₃ group (in which R ²⁶ each independently represents a C _1-8 alkyl group) or a -OR ²⁷ group (in which R ²⁷ is a hydrogen atom, C denotes a C _1-8 alkyl group substituted by _{1 to 8} represents an alkyl group or a C _2~5 acyl),
R ¹⁹ is
(i) a hydrogen atom,
(ii) a C _1-8 alkyl group,
(iii) a phenyl group or
(iv) a C _1-8 alkyl group substituted with a phenyl group,
R ²⁰ is
(i) a hydrogen atom,
(ii) a C _1-8 alkyl group,
(iii) a group -C (O) R ^{28 wherein} R ²⁸ is a C _1-8 alkyl group, a C _1-8 alkoxy group, a Cyc ¹ group or a NR ²⁹ R ³⁰ group (in which R ²⁹ and R ³⁰ are Each independently represents a hydrogen atom or a C _1-8 alkyl group)),
(iv) Cyc ¹ or a group
(v) Cyc represents a C _1~8 alkyl group substituted with ^one group or cyano group,
R ²¹ is
(i) a hydrogen atom,
(ii) a C _1-8 alkyl group or
(iii) represents a group Cyc ^1,
Cyc ¹
(i) a monocyclic C of _{3 to 15,} bicyclic, tricyclic carbon ring or triple
(ii) a single, double or triple cyclic heterocycle of 4 to 18 members including 1 to 4 nitrogen atoms, 1 to 2 oxygen atoms and / or 1 sulfur atom,
These carbocyclic or heterocyclic rings may contain one or more
(i) C _1~8 alkyl group, (ii) C _2~8 alkenyl group, (iii) C _2~8 alkynyl group, (iv) oxo, (v) cyano, (vi) nitro groups, (vii) A trihalomethyl group, (iii) a halogen atom, (x) a diphenylmethyl group, (xi) a triphenylmethyl group, (xii) a Cyc ² group, (xiii) -OR ³¹ group, xiv) -SR ³² group, (xv) -NR ³³ R ^{34 _{group, (xvi) -SO 2 NR 35}} R 36 group, (xvii) -C (O) R 37 group, or (xviii) Cyc ² group, a hydroxyl group, A halogen atom or a C _1-8 alkyl group substituted with a -C (O) -Cyc ² group, a C _2-8 alkenyl group or a C _2-8 alkynyl group, R ³¹ and R ³² each independently represent a hydrogen atom , A C _1-8 alkyl group or a Cyc ² group,
R ³³ represents a hydrogen atom or a C _1-8 alkyl group,
R ³⁴ represents a hydrogen atom, a C _1-8 alkyl group or a -C (O) -Cyc ² group,
R ³⁵ represents a hydrogen atom or a C _1-8 alkyl group,
R ³⁶ represents a hydrogen atom, a C _1-8 alkyl group or a Cyc ² group,
R ³⁷ is a hydrogen atom, C _1~8 alkyl groups, -OR ³⁸ groups, -NR ³⁹ R ⁴⁰ group, Cyc ² group or a group Cyc ² or -C (O) -Cyc ² represents a C _1~8 alkyl group substituted by ,
R ³⁸ , R ³⁹ and R ⁴⁰ each independently represent a hydrogen atom or a C _1-8 alkyl group which may be substituted with Cyc ² ,
Cyc ²
(i) a monocyclic C of _{3 to 15,} bicyclic, tricyclic carbon ring or triple
(ii) a single, double or triple cyclic heterocycle of 4 to 18 members including 1 to 4 nitrogen atoms, 1 to 2 oxygen atoms and / or 1 sulfur atom,
These carbocyclic or heterocyclic rings may contain one or more
(i) C _1~8 alkyl group, (ii) C _2~8 alkenyl group, (iii) C _2~8 alkynyl group, (iv) oxo, (v) cyano, (vi) nitro groups, (vii) trihaloalkyl group, (viii) Romero Talk time trihalomethyl, (ix) halogen atoms, (x) -OR ⁴¹ group, (xi) -SR ⁴² group, (xii) -NR ⁴³ R ⁴⁴ group, (xiii) - SO ₂ NR ⁴⁵ R ⁴⁶ group, (xiv) -C (O) R ⁴⁷ group, (xv) a C _1-8 alkyl group, a C _2-8 alkenyl group or a C _2-8 alkynyl group substituted with a hydroxyl group or a halogen atom xvi) may be substituted with a phenyl group,
R ⁴¹ , R ⁴² , R ⁴³ , R ⁴⁴ , R ⁴⁵ and R ⁴⁶ each independently represent a hydrogen atom or a C _1-8 alkyl group,
R ⁴⁷ represents a hydrogen atom, a C _1-8 alkyl group or a C _1-8 alkoxy group,
q R &lt; ² &gt; are each independently,
(i) a C _1-8 alkyl group,
(ii) a C _2-8 alkenyl group,
(iii) a C _2-8 alkynyl group,
(iv) -OR ⁴⁸ groups,
(v) -NR ⁴⁹ R ⁵⁰ group,
(vi) -C (O) R &lt; ^{51 &gt;} groups,
(vii) a nitro group,
(viii) a cyano group,
(ix) a halogen atom or
(x) -OR ⁴⁸ group, -NR ⁴⁹ R ⁵⁰ group, -C (O) R ⁵¹ group, C _1-8 alkyl group substituted by halogen atom or Cyc ³ group, C _2-8 alkenyl group or C _2-8 Alkynyl group,
R ⁴⁸ is
(i) a hydrogen atom,
(ii) a C _1-8 alkyl group,
(iii) a C _2-8 alkenyl group,
(iv) a C _2-8 alkynyl group,
(v) Cyc group ³ or
(vi) a C _1-8 alkyl group substituted by a halogen atom, -OR ⁵² group, -NR ⁵³ R ⁵⁴ group, -C (O) R ⁵⁵ group or Cyc ³ group, C _2-8 alkenyl group or C _2-8 An alkynyl group,
R ⁴⁹ and R ⁵⁰ each independently represent a hydrogen atom, a C _1-8 alkyl group or a -COR ⁵⁹ group,
R ⁵¹ represents a hydrogen atom, a C _1-8 alkyl group, a hydroxyl group, a C _1-8 alkoxy group or an -NR ⁶⁰ R ⁶¹ group,
R ⁵² represents a hydrogen atom, a C _1-8 alkyl group, a Cyc ³ group or a C _1-8 alkyl group substituted with a Cyc ³ group,
R ⁵³ and R ⁵⁴ each independently represent a hydrogen atom, C _1~8 alkyl, C _2~8 alkenyl, C _2~8 alkynyl group or -C (O) R ⁵⁶ group (a group, R ⁵⁶ is C _{1~ A} C _1-8 alkoxy group, a Cyc ³ group or a Cyc ³ group substituted with a C _1-8 alkyl group, a C _1-8 alkoxy group, a Cyc ³ group or a Cyc ³ group), R ⁵⁵ represents a hydroxyl group, a C _1-8 alkoxy group or a -NR ⁵⁷ R ⁵⁸ group , R ⁵⁷ and R ⁵⁸ each independently represent a hydrogen atom, a C _1-8 alkyl group or a C _1-8 alkyl group substituted with a Cyc ³ group,
R ⁵⁹ represents a C _1-8 alkyl group or a C _1-8 alkoxy group,
R ⁶⁰ and R ⁶¹ each independently represent a hydrogen atom or a C _1-8 alkyl group,
Cyc ³
(i) a monocyclic C of _{3 to 15,} bicyclic, tricyclic carbon ring or triple
(ii) a single, double or triple cyclic heterocycle of 4 to 18 members including 1 to 4 nitrogen atoms, 1 to 2 oxygen atoms and / or 1 sulfur atom,
These carbocyclic or heterocyclic rings may contain one or more
(i) C _1~8 alkyl group, (ii) C _1~8 alkoxy group, (iii) nitro group, (iv) halogen atom, (v) cyano, (vi) hydroxy group, (vii) benzyloxy group, ( (viii) -NR ⁶² R ⁶³ group, (ix) -COOR ⁶⁴ group, (x) trihalomethyl group, (xi) trihalomethoxy group, (xii) phenyl group, (Xv) a C _1-8 alkyl group substituted with a phenyl group, a phenoxy group, a phenylthio group, a hydroxyl group, a -NR ⁶² R ⁶³ group or a -COOR ⁶⁴ group, or a C _1-8 alkoxy group,
R ⁶² and R ⁶³ each independently represent a hydrogen atom or a C _1-8 alkyl group,
R ⁶⁴ represents a hydrogen atom or a C _1-8 alkyl group.
only,
A ² is (vi) -NR ⁵ C (O) - group, (x) -NR ⁷ SO ₂ - group, (xiv) -NR ¹³ C (O) O- group or (xv) -, A &lt; ³ &gt; is not a hydrogen atom.
[2" claim-type="Currently amended] A pharmaceutical composition for preventing or treating inflammatory diseases, sepsis, multiple myeloma, plasma cell leukemia, osteoporosis, cachexia, psoriasis, osteoporosis, osteoporosis, , Psoriasis, nephritis, renal cell carcinoma, Kaposi sarcoma, chronic arthritic rheumatism, hypergammaglobulinemia, castor mania, atrial myxoma, diabetes, autoimmune disease, hepatitis, multiple sclerosis, colitis, graft versus host disease, / Or therapeutic agent.
[3" claim-type="Currently amended] 2. The method of claim 1,
(1) 3- (thiophen-2-yl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(2) 6-Nitro-3- (thiophen-2-yl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(3) Synthesis of 3- (thiophen-2-yl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
(4) 4,5-dimethyl-1,1-dioxide benzo [b] thiophene,
(5) 4,6-dimethyl-1,1-dioxide benzo [b] thiophene,
(6) 4,7-dimethyl-1,1-dioxide benzo [b] thiophene,
(7) 5,6-dimethyl-1,1-dioxide benzo [b] thiophene,
(8) 5,7-dimethyl-1,1-dioxide benzo [b] thiophene,
(9) 6,7-dimethyl-1,1-dioxide benzo [b] thiophene,
(10) 4-carboxymethyl-1,1-dioxide benzo [b] thiophene,
(11) 6- (2,2-bis (ethoxycarbonyl) ethenyl) amino-1,1-dioxide benzo [b] thiophene,
(12) 4-Methylaminocarbonyloxy-1, 1-dioxo [b] thiophene,
(13) 5- (2- (N- (5-Methoxy-1,2,3,4-tetrahydronaphthalen-1-ylmethyl) b] thiophene,
(14) 5- (2-hydroxyethyl) -1,1-dioxo [b] thiophene,
(15) 5-Bromo-7-methyl-l, l-dioxide benzo [b] thiophene,
(16) 7-Bromo-5-methyl-l, l-dioxide benzo [b] thiophene,
(17) 5-Bromo-6-methyl-l, l-dioxide benzo [b] thiophene,
(18) 5-bromo-4-methyl-l, l-dioxide benzo [b] thiophene,
(19) 6-bromo-5-methyl-l, l-dioxide benzo [b] thiophene,
(20) 4-Bromo-5-methyl-l, l-dioxide benzo [b] thiophene,
(21) 6-amino-1,1-dioxide benzo [b] thiophene,
(22) 6-acetylamino-l, l-dioxide benzo [b] thiophene,
(23) 6- (4-Diethylaminophenyl) -1,1-dioxo [b] thiophene,
(24) 1,1-dioxo-thieno [2,3-b] pyridine,
(25) 1,1-dioxo-thieno [3,2-b] pyridine,
(26) 1,1-dioxo-thieno [2,3-c] pyridine,
(27) 5-amino-1,1-dioxide benzo [b] thiophene,
(28) 5- (3-methyl-5-oxo-4,5-dihydropyrazol-1-yl) -1,1-dioxide benzo [b] thiophene,
(29) 4- (2- (1,1-dioxide benzo [b] thiophen-3-yl) ethyl) -1,1-dioxide benzo [b] thiophene,
(30) 7-methyl-1,1-dioxo [b] thieno [2,3-c] pyridine,
(31) 1,1-dioxide benzo [b] thiophene,
(32) 4- (4-methoxyphenyl) -1,1-dioxide thieno [3,2-c] pyridine,
(33) 5 - ((E) -2- (ethoxycarbonyl) ethenyl-4-methoxybenzo [b] thiophene,
(34) 5- (2- (ethoxycarbonyl) ethyl) -4-methoxybenzo [b] thiophene,
(35) 5-Methoxycarbonyl-4-ethoxybenzo [b] thiophene,
(36) 5-Carboxy-4-ethoxybenzo [b] thiophene,
(37) 5-Benzyloxycarbonyl-4-ethoxybenzo [b] thiophene,
(38) 5-hydroxy-4-formylbenzo [b] thiophene,
(39) 5-Benzyloxy-4-formylbenzo [b] thiophene,
(40) 5-Benzyloxy-4-hydroxymethylbenzo [b] thiophene,
(41) 4-t-Butoxycarbonylaminobenzo [b] thiophene,
Or an N-oxide derivative thereof or a non-toxic salt thereof as an active ingredient.
[4" claim-type="Currently amended] A novel condensed thiophene derivative represented by the following formula (IA), an N-oxide derivative thereof or a non-toxic salt thereof.
&Lt;

In the above formulas, Represents a single bond or a double bond,
Y is

or
(ii) a hydrogen atom,
(only, Represents a double bond, Y represents a hydrogen atom,
Is a single bond, Y is Lt; / RTI &gt;
m and n each independently represent 0 or an integer of 1 to 2,
p represents 0 or an integer of 1 to 4,
q represents 0 or an integer of 1 to 5,
Z represents a single bond, a C _1-8 alkylene group, a C _2-8 alkenylene group or a C _2-8 alkynylene group,
silver
(i) a benzene ring or
(ii) a 6-membered monocyclic heterocyclic aryl containing 1 to 2 nitrogen atoms,
The
(i) a monocyclic C of _{3 to 15,} bicyclic, tricyclic carbon ring or triple
(ii) a single, double or triple cyclic heterocycle of 4 to 18 members including 1 to 4 nitrogen atoms, 1 to 2 oxygen atoms and / or 1 sulfur atom,
p &lt; RTI ID = 0.0 &gt; Ri &lt; / RTI &^gt;
(i) a C _1-8 alkyl group,
(ii) a C _2-8 alkenyl group,
(iii) a C _2-8 alkynyl group,
(iv) a nitro group,
(v) a cyano group,
(vi) a halogen atom,
(vii) Cyc ¹ group,
(viii) a C _1-8 alkyl group, a C _2-8 alkenyl group or a C _2-8 alkynyl group substituted by a halogen atom or a Cyc ¹ group, or
(ix) -A ¹ -A ² -A ³ ,
A ¹ is
(i) single bond,
(ii) C_1-8 Alkylene group,
(iii) a C _2-8 alkenylene group or
(iv) a C _2-8 alkynylene group,
A ² is
(i) -O- group,
(ii) -NR ³ - group,
(iii) -C (O) - group,
(iv) -CH (OH) - group,
(v) -C (O) NR 4 - group,
(vi) -NR &lt; ⁵ &gt; C (O)
(vii) -C (O) O- group,
(viii) -OC (O) - group,
(ix) -SO ₂ NR ⁶ - group,
(x) -NR ⁷ SO ₂ - group,
(xi) -C (O) NR &lt; ⁹ &gt; O- group,
(xii) -OC (O) NR &lt; ¹⁰ &gt; - group,
(xiii) -NR ¹¹ C (O) NR ¹² - group,
(xiv) -NR &lt; ¹³ &gt; C (O) O- group or
(xv) -OC (O) O- group,
(Wherein R ³ , R ⁴ , R ⁵ , R ⁶ , R ⁷ , R ⁹ , R ¹⁰ , R ¹¹ , R ¹² and R ¹³ each independently represent a hydrogen atom, a C _1-8 alkyl group, ¹ group, a -OR ¹⁴ group (in which R ¹⁴ represents a hydrogen atom or a C _1-8 alkyl group) or a C _1-8 alkyl group substituted with a cyano group, and each group represented by A ² represents a The combined hand is coupled to A ³ ),
A ³ is
(i) a hydrogen atom,
(ii) a C _1-8 alkyl group,
(iii) a C _2-8 alkenyl group,
(iv) a C _2-8 alkynyl group,
(v) Cyc group ¹ or
(vi) a C _1-8 alkyl group, a C _2-8 alkenyl group or a C _2-8 alkynyl group substituted with 1 to 3 groups selected from the following (a) to (i)
(a) a halogen atom,
(b) a cyano group,
(c) -P (O) (R ¹⁵ ) ₂ group,
^{(d) -Si (R 16)} 3 group,
(e) Cyc ¹ group,
(f) -C (O) R &lt; ¹⁷ &gt; groups,
(g) -OR ¹⁸ groups,
(h) -NR ¹⁹ R ²⁰ group,
(i) -SR ²¹ group;
A plurality of R ¹⁵ present each independently represent a hydroxyl group or C _1~8 alkoxy,
A plurality of R &lt; ¹⁶ &gt; each independently represent a C _1-8 alkyl group,
R ¹⁷ is
(i) a hydrogen atom,
(ii) a C _1-8 alkyl group,
(iii) a hydroxyl group,
(iv) a C _1-8 alkoxy group,
(v) Cyc group ¹ or
(vi) -NR ²² R ²³ group (in which, R ²² represents a C _1~8 alkyl group substituted by a hydrogen atom, C _1~8 alkyl group, a phenyl group, a phenyl group, R ²³ is a hydrogen atom, C _1~8 alkyl group , Cyc substituted with ¹ group Cyc ¹ or a group or an NR ²⁴ R ²⁵ group (R ²⁴ and R ²⁵ represents a C _1~8 alkyl group substituted by a hydrogen atom, C _1~8 alkyl group, a phenyl group, a phenyl group, each independently) A C _1-8 alkyl group)
R ¹⁸ is
(i) a hydrogen atom,
(ii) a C _1-8 alkyl group,
(iii) a C _2-8 alkenyl group,
(iv) Cyc ¹ or a group
(v) a Cyc ¹ group, a Si (R ²⁶ ) ₃ group (in which R ²⁶ each independently represents a C _1-8 alkyl group) or a -OR ²⁷ group (in which R ²⁷ is a hydrogen atom, C denotes a C _1-8 alkyl group substituted by _{1 to 8} represents an alkyl group or a C _2~5 acyl),
R ¹⁹ is
(i) a hydrogen atom,
(ii) a C _1-8 alkyl group,
(iii) a phenyl group or
(iv) a C _1-8 alkyl group substituted with a phenyl group,
R ²⁰ is
(i) a hydrogen atom,
(ii) a C _1-8 alkyl group,
(iii) a group -C (O) R ^{28 wherein} R ²⁸ is a C _1-8 alkyl group, a C _1-8 alkoxy group, a Cyc ¹ group or a NR ²⁹ R ³⁰ group (in which R ²⁹ and R ³⁰ are Each independently represents a hydrogen atom or a C _1-8 alkyl group)),
(iv) Cyc ¹ or a group
(v) Cyc represents a C _1~8 alkyl group substituted with ^one group or cyano group,
R ²¹ is
(i) a hydrogen atom,
(ii) a C _1-8 alkyl group or
(iii) represents a group Cyc ^1,
Cyc ¹
(i) a monocyclic C of _{3 to 15,} bicyclic, tricyclic carbon ring or triple
(ii) a single, double or triple cyclic heterocycle of 4 to 18 members including 1 to 4 nitrogen atoms, 1 to 2 oxygen atoms and / or 1 sulfur atom,
These carbocyclic or heterocyclic rings may contain one or more
(i) C _1~8 alkyl group, (ii) C _2~8 alkenyl group, (iii) C _2~8 alkynyl group, (iv) oxo, (v) cyano, (vi) nitro groups, (vii) A trihalomethyl group, (iii) a halogen atom, (x) a diphenylmethyl group, (xi) a triphenylmethyl group, (xii) a Cyc ² group, (xiii) -OR ³¹ group, xiv) -SR ³² group, (xv) -NR ³³ R ^{34 _{group, (xvi) -SO 2 NR 35}} R 36 group, (xvii) -C (O) R 37 group, or (xviii) Cyc ² group, a hydroxyl group, A halogen atom or a C _1-8 alkyl group substituted with a -C (O) -Cyc ² group, a C _2-8 alkenyl group or a C _2-8 alkynyl group, R ³¹ and R ³² each independently represent a hydrogen atom , A C _1-8 alkyl group or a Cyc ² group,
R ³³ represents a hydrogen atom or a C _1-8 alkyl group,
R ³⁴ represents a hydrogen atom, a C _1-8 alkyl group or a -C (O) -Cyc ² group,
R ³⁵ represents a hydrogen atom or a C _1-8 alkyl group,
R ³⁶ represents a hydrogen atom, a C _1-8 alkyl group or a Cyc ² group,
R ³⁷ is a hydrogen atom, C _1~8 alkyl groups, -OR ³⁸ groups, -NR ³⁹ R ⁴⁰ group, Cyc ² group or a group Cyc ² or -C (O) -Cyc ² represents a C _1~8 alkyl group substituted by ,
R ³⁸ , R ³⁹ and R ⁴⁰ each independently represent a hydrogen atom or a C _1-8 alkyl group which may be substituted with Cyc ² ,
Cyc ²
(i) a monocyclic C of _{3 to 15,} bicyclic, tricyclic carbon ring or triple
(ii) a single, double or triple cyclic heterocycle of 4 to 18 members including 1 to 4 nitrogen atoms, 1 to 2 oxygen atoms and / or 1 sulfur atom,
These carbocyclic or heterocyclic rings may contain one or more
(i) C _1~8 alkyl group, (ii) C _2~8 alkenyl group, (iii) C _2~8 alkynyl group, (iv) oxo, (v) cyano, (vi) nitro groups, (vii) trihaloalkyl group, (viii) Romero Talk time trihalomethyl, (ix) halogen atoms, (x) -OR ⁴¹ group, (xi) -SR ⁴² group, (xii) -NR ⁴³ R ⁴⁴ group, (xiii) - SO ₂ NR ⁴⁵ R ⁴⁶ group, (xiv) -C (O) R ⁴⁷ group, (xv) a C _1-8 alkyl group, a C _2-8 alkenyl group or a C _2-8 alkynyl group substituted with a hydroxyl group or a halogen atom xvi) phenyl group,
R ⁴¹ , R ⁴² , R ⁴³ , R ⁴⁴ , R ⁴⁵ and R ⁴⁶ each independently represent a hydrogen atom or a C _1-8 alkyl group,
R ⁴⁷ represents a hydrogen atom, a C _1-8 alkyl group or a C _1-8 alkoxy group,
q R &lt; ² &gt; are each independently,
(i) a C _1-8 alkyl group,
(ii) a C _2-8 alkenyl group,
(iii) a C _2-8 alkynyl group,
(iv) -OR ⁴⁸ groups,
(v) -NR ⁴⁹ R ⁵⁰ group,
(vi) -C (O) R &lt; ^{51 &gt;} groups,
(vii) a nitro group,
(viii) a cyano group,
(ix) a halogen atom or
(x) -OR ⁴⁸ group, -NR ⁴⁹ R ⁵⁰ group, -C (O) R ⁵¹ group, C _1-8 alkyl group substituted by halogen atom or Cyc ³ group, C _2-8 alkenyl group or C _2-8 Alkynyl group,
R ⁴⁸ is
(i) a hydrogen atom,
(ii) a C _1-8 alkyl group,
(iii) a C _2-8 alkenyl group,
(iv) a C _2-8 alkynyl group,
(v) Cyc group ³ or
(vi) a C _1-8 alkyl group substituted by a halogen atom, -OR ⁵² group, -NR ⁵³ R ⁵⁴ group, -C (O) R ⁵⁵ group or Cyc ³ group, C _2-8 alkenyl group or C _2-8 An alkynyl group,
R ⁴⁹ and R ⁵⁰ each independently represent a hydrogen atom, a C _1-8 alkyl group or a -COR ⁵⁹ group,
R ⁵¹ represents a hydrogen atom, a C _1-8 alkyl group, a hydroxyl group, a C _1-8 alkoxy group or an -NR ⁶⁰ R ⁶¹ group,
R ⁵² represents a hydrogen atom, a C _1-8 alkyl group, a Cyc ³ group or a C _1-8 alkyl group substituted with a Cyc ³ group,
R ⁵³ and R ⁵⁴ each independently represent a hydrogen atom, C _1~8 alkyl, C _2~8 alkenyl, C _2~8 alkynyl group or -C (O) R ⁵⁶ group (a group, R ⁵⁶ is C _{1~ A} C _1-8 alkoxy group, a Cyc ³ group or a Cyc ³ group substituted with a C _1-8 alkyl group, a C _1-8 alkoxy group, a Cyc ³ group or a Cyc ³ group), R ⁵⁵ represents a hydroxyl group, a C _1-8 alkoxy group or a -NR ⁵⁷ R ⁵⁸ group , R ⁵⁷ and R ⁵⁸ each independently represent a hydrogen atom, a C _1-8 alkyl group or a C _1-8 alkyl group substituted with a Cyc ³ group)
R ⁵⁹ represents a C _1-8 alkyl group or a C _1-8 alkoxy group,
R ⁶⁰ and R ⁶¹ each independently represent a hydrogen atom or a C _1-8 alkyl group,
Cyc ³
(i) a monocyclic C of _{3 to 15,} bicyclic, tricyclic carbon ring or triple
(ii) a single, double or triple cyclic heterocycle of 4 to 18 members including 1 to 4 nitrogen atoms, 1 to 2 oxygen atoms and / or 1 sulfur atom,
These carbocyclic or heterocyclic rings may contain one or more
(i) C _1~8 alkyl group, (ii) C _1~8 alkoxy group, (iii) nitro group, (iv) halogen atom, (v) cyano, (vi) hydroxy group, (vii) benzyloxy group, ( (viii) -NR ⁶² R ⁶³ group, (ix) -COOR ⁶⁴ group, (x) trihalomethyl group, (xi) trihalomethoxy group, (xii) phenyl group, (Xv) a C _1-8 alkyl group substituted with a phenyl group, a phenoxy group, a phenylthio group, a hydroxyl group, a -NR ⁶² R ⁶³ group or a -COOR ⁶⁴ group, or a C _1-8 alkoxy group,
R ⁶² and R ⁶³ each independently represent a hydrogen atom or a C _1-8 alkyl group,
R ⁶⁴ represents a hydrogen atom or a C _1-8 alkyl group. only,
(a) A ² is (vi) -NR ⁵ C (O) - group, (x) -NR ⁷ SO ₂ - group, (xiv) -NR ¹³ C (O) O- group or O) O- group, A ³ does not denote a hydrogen atom,
(b) Represents a double bond, and when Y represents a hydrogen atom, n represents 1 or 2,
(c) Represents a single bond, and Y represents N represents 2, m represents 0 or 2, p represents 0 or an integer of 1 to 4, A ring and B ring represent a benzene ring, R ¹ represents a C _1-8 alkyl group, C _{1 to 8} alkoxy group, to represent a halogen atom, a carboxyl group, a nitro group or a halogen atom substituted with C _1~8 alkyl group, q is, and that does not represent an O,
(d) Represents a single bond, and Y represents , N represents 2, m represents 0 or 2, p represents 0 or an integer of 1 to 4, A ring and B ring represent a benzene ring, R ¹ represents a C _1-8 alkyl group, C _{1 to 8} alkoxy group, a halogen atom, a carboxy group, a denotes a nitro group or a halogen atom substituted with C _1~8 alkyl group, when the q represent an integer of 1~5, R ² is C _1~8 alkyl, C _1~8 alkoxy A halogen atom, a carboxy group, a nitro group, or a C _1-8 alkyl group substituted with a halogen atom,
(e) When Y represents a hydrogen atom, n represents 2, p represents 1, and the ring A represents a benzene ring, R ¹ represents a halogen atom, a C _1-8 alkyl group, a phenylsulfonylamino group, Substituted with a C _1-8 alkoxycarbonyl group or a hydroxymonocarbonyl group, a hydroxyl group, a C _1-8 alkoxy group, a nitro group or a carboxy group, a hydroxyl group, a C _1-8 alkoxycarbonyl group or a hydroxyminocarbonyl group, _{Lt; RTI} ID = 0.0 &gt; _C8 &lt; / RTI &gt; alkoxy group,
(f) Y represents a hydrogen atom, n represents 2, p represents 2, A ring represents a benzene ring, one R ¹ represents a phenylsulfonylamino group, a 2-methylphenylsulfonylamino group, a 3-methylphenylsulfonylamino group, A methylphenylsulfonylamino group or a 4-methylphenylsulfonylamino group, another R ¹ is not a C _1-8 alkyl group,
(g) Y represents a hydrogen atom, n represents 2, p represents 2 to 3, A ring represents a benzene ring, one R ¹ represents a hydroxyl group, a C _1-8 alkoxy group or a carboxyl group, to indicate a hydroxyl group, C _1~8 alkoxycarbonyl group or a hydroxy C _1~8 alkoxy substituted with amino group, and the other R ¹ is and that it does not represent a halogen atom or a C _1~8 alkyl group,
(h) Y represents a hydrogen atom, n represents 2, p represents 3 to 4, and when A ring represents a benzene ring, 2 to 3 R ¹ do not simultaneously represent a t-butyl group and,
(i) Excludes the following compounds (1) to (32):
(1) 3- (thiophen-2-yl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(2) 6-Nitro-3- (thiophen-2-yl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(3) Synthesis of 3- (thiophen-2-yl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene
(4) 4,5-dimethyl-1,1-dioxide benzo [b] thiophene,
(5) 4,6-dimethyl-1,1-dioxide benzo [b] thiophene,
(6) 4,7-dimethyl-1,1-dioxide benzo [b] thiophene,
(7) 5,6-dimethyl-1,1-dioxide benzo [b] thiophene,
(8) 5,7-dimethyl-1,1-dioxide benzo [b] thiophene,
(9) 6,7-dimethyl-1,1-dioxide benzo [b] thiophene,
(10) 4-carboxymethyl-1,1-dioxide benzo [b] thiophene,
(11) 6- (2,2-bis (ethoxycarbonyl) ethenyl) amino-1,1-dioxide benzo [b] thiophene,
(12) 4-Methylaminocarbonyloxy-1, 1-dioxo [b] thiophene,
(13) 5- (2- (N- (5-Methoxy-1,2,3,4-tetrahydronaphthalen-1-ylmethyl) b] thiophene,
(14) 5- (2-hydroxyethyl) -1,1-dioxo [b] thiophene,
(15) 5-Bromo-7-methyl-l, l-dioxide benzo [b] thiophene,
(16) 7-Bromo-5-methyl-l, l-dioxide benzo [b] thiophene,
(17) 5-Bromo-6-methyl-l, l-dioxide benzo [b] thiophene,
(18) 5-bromo-4-methyl-l, l-dioxide benzo [b] thiophene,
(19) 6-bromo-5-methyl-l, l-dioxide benzo [b] thiophene,
(20) 4-Bromo-5-methyl-l, l-dioxide benzo [b] thiophene,
(21) 6-amino-1,1-dioxide benzo [b] thiophene,
(22) 6-acetylamino-l, l-dioxide benzo [b] thiophene,
(23) 6- (4-Diethylaminophenyl) -1,1-dioxo [b] thiophene,
(24) 1,1-dioxo-thieno [2,3-b] pyridine,
(25) 1,1-dioxo-thieno [3,2-b] pyridine,
(26) 1,1-dioxo-thieno [2,3-c] pyridine,
(27) 5-amino-1,1-dioxide benzo [b] thiophene,
(28) 5- (3-methyl-5-oxo-4,5-dihydropyrazol-1-yl) -1,1-dioxide benzo [b] thiophene,
(29) 4- (2- (1,1-dioxide benzo [b] thiophen-3-yl) ethyl) -1,1-dioxide benzo [b] thiophene,
(30) 7-methyl-1,1-dioxo [b] thieno [2,3-c] pyridine,
(31) 1,1-dioxide benzo [b] thiophene or
(32) 4- (4-methoxyphenyl) -1,1-dioxo-thieno [3,2-c] pyridine].
[5" claim-type="Currently amended] 5. The method of claim 4, Is a double bond, an N-oxide derivative thereof or a non-toxic salt thereof.
[6" claim-type="Currently amended] 5. The method of claim 4, Are single bonds, condensed thiophene derivatives represented by the formula (IA), N-oxide derivatives thereof or non-toxic salts thereof.
[7" claim-type="Currently amended] 5. The method of claim 4, Is a benzene ring, an N-oxide derivative thereof, or a non-toxic salt thereof.
[8" claim-type="Currently amended] 5. The method of claim 4, Is a 6-membered monocyclic hetero ring aryl containing 1 to 2 nitrogen atoms, condensed thiophene derivatives thereof, N-oxide derivatives thereof or nontoxic salts thereof.
[9" claim-type="Currently amended] 5. The method of claim 4, Is a single ring, double ring or tricyclic carbon ring of C ₃ to ₁₅ , condensed thiophene derivatives represented by the formula (IA), N-oxide derivatives thereof or nontoxic salts thereof.
[10" claim-type="Currently amended] 5. The method of claim 4, Is a 4-membered single ring, double ring or triple ring hetero ring containing 1 to 4 nitrogen atoms, 1 to 2 oxygen atoms and / or 1 sulfur atom, a condensed thiophene derivative represented by the formula (IA) N-oxide derivatives or non-toxic salts thereof.
[11" claim-type="Currently amended] 5. The method of claim 4, Is a single ring, double ring or triple cyclic heterocycle of 5 to 10 members including 1 to 4 nitrogen atoms, 1 to 2 oxygen atoms and / or 1 sulfur atom, a condensed thiophene derivative represented by the formula (IA) N-oxide derivatives thereof or non-toxic salts thereof.
[12" claim-type="Currently amended] 5. The method of claim 4, A condensed thiophene derivative represented by the formula (IA) wherein the condensed thiophene derivative is a single ring, double ring or triple cyclic heterocycle of 11 to 18 members including 1 to 4 nitrogen atoms, 1 to 2 oxygen atoms and / or 1 sulfur atom, N-oxide derivatives thereof or non-toxic salts thereof.
[13" claim-type="Currently amended] 5. The compound according to claim 4,
(1) 3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(2) 3- (thiophen-2-yl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(3) 3- (4-methylphenyl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(4) 3- (4-methoxyphenyl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(5) 3- (4-chlorophenyl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(6) 3- (4-fluorophenyl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(7) 3- (4-hydroxyphenyl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(8) 3- (3-hydroxyphenyl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(9) 3- (2-hydroxyphenyl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(10) 3- (Pyridin-4-yl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(11) 3- (Pyrimidin-2-yl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(12) 3- (Thiazol-2-yl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(13) 3- (3-methylfuran-2-yl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(14) 3- (3-methoxyphenyl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(15) 3- (2-methoxycarbonylphenyl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(16) 3-Cyclohexylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(17) 3- (naphthalen-1-yl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(18) 3- (2-methoxyphenyl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(19) 3- (1-methylimidazol-2-yl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(20) 3-phenylsulfinyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(21) 3- (thiophen-2-yl) sulfinyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(22) 3- (2-methoxycarbonylphenyl) sulfinyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(23) 3-Phenylsulfonyl-2,3-dihydro-1, 1-dioxide benzo [b] thiophene,
(24) 3- (thiophen-2-yl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(25) 3- (4-methylphenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(26) 3- (4-methoxyphenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(27) 3- (4-Chlorophenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(28) 3- (4-fluorophenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(29) 3- (4-hydroxyphenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(30) 3- (3-hydroxyphenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(31) 3- (2-hydroxyphenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(32) 3- (Pyridin-4-yl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(33) 3- (Pyrimidin-2-yl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(34) 3- (Thiazol-2-yl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(35) 3- (3-methylfuran-2-yl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(36) 3- (3-Methoxyphenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(37) 3- (2-Methoxycarbonylphenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(38) 3-cyclohexylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(39) 3- (Naphthalen-1-yl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(40) 3- (2-methoxyphenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(41) 3- (4- (2- (Piperidin-1-yl) ethoxy) phenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(42) Synthesis of 3- (4- (2- (pyrrolidin-1-yl) ethoxy) phenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(43) Synthesis of 3- (4- (2- (morpholin-4-yl) ethoxy) phenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(44) 3- (3-benzyloxyphenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(45) 3- (2-benzyloxyphenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(46) 3- (4- (pyridin-2-ylmethyloxy) phenyl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(47) 3- (4- (pyridin-3-ylmethyloxy) phenyl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(48) 3- (4- (pyridin-4-ylmethyloxy) phenyl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(49) 3- (4- (3-Hydroxypropyloxy) phenyl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(50) 3- (3- (pyridin-3-ylmethyloxy) phenyl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(51) 3- (3- (3-Hydroxypropyloxy) phenyl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(52) 3- (2- (pyridin-3-ylmethyloxy) phenyl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(53) 3- (2- (3-Hydroxypropyloxy) phenyl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(54) 3- (4- (2- (t-butoxycarbonylamino) ethyloxy) phenyl) thio-2,3-dihydro- 1,1-dioxide benzo [b] thiophene,
(55) 3- (3- (2- (t-butoxycarbonylamino) ethyloxy) phenyl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(56) 3- (4- (pyridin-2-ylmethyloxy) phenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(57) 3- (4- (pyridin-3-ylmethyloxy) phenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(58) 3- (4- (pyridin-4-ylmethyloxy) phenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(59) 3- (4- (3-Hydroxypropyloxy) phenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(60) 3- (3- (pyridin-3-ylmethyloxy) phenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(61) 3- (3- (3-Hydroxypropyloxy) phenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(62) 3- (2- (pyridin-3-ylmethyloxy) phenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(63) 3- (2- (3-hydroxypropyloxy) phenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(64) Synthesis of 3- (4- (2- (t-butoxycarbonylamino) ethyloxy) phenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(65) 3- (3- (2- (t-butoxycarbonylamino) ethyloxy) phenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(66) 3- (4- (2-aminoethyloxy) phenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(67) 3- (3- (2-aminoethyloxy) phenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(68) 3- (4- (2- (N, N-dimethylamino) ethyloxy) phenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(69) 3- (3- (2- (N, N-dimethylamino) ethyloxy) phenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(70) 5-Nitro-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(71) 6-Methoxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(72) 4-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(73) Synthesis of 5-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(74) 7-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(75) 4-Chloro-3-phenylthio-2,3-dihydro-1,1-dioxo benzo [b] thiophene,
(76) 5- (t-Butoxycarbonylamino) methyl-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(77) 4,7-dimethyl-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(78) 4,6-dimethyl-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(79) 4-Ethyl-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(80) 4-methoxy-5-ethoxycarbonyl-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(81) 4-Bromo-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(82) 4-Hydroxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(83) 5-Hydroxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(84) 6-Hydroxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(85) 7-hydroxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(86) 3-phenylthio-2,3-dihydro-1,1-dioxo thieno [2,3- b] (87) 4,7-dihydroxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(88) 5-Nitro-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(89) 6-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(90) 4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(91) 5-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(92) 7-Methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(93) 4-Chloro-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide [
(94) 4- (t-Butoxycarbonylamino) methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(95) 4,7-dimethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(96) 4,6-dimethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(97) 4-ethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(98) 4-Methoxy-5-ethoxycarbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(99) 4-Bromo-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(100) 4-hydroxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(101) 5-hydroxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(102) 6-hydroxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(103) 7-hydroxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(104) 3-phenylsulfonyl-2,3-dihydro-1,1-dioxo thieno [2,3- b] (105) 5-amino-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(106) 5-Acetylamino-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(107) 4-Aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxa benzo [b] thiophene,
(108) 4- (N, N-dimethylamino) methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(109) 4-methoxy-5-formyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(110) 4-methoxy-3- (thiophen-2-yl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(111) 4-methoxy-3- (thiophen-2-yl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(112) 4- (4-nitrophenylmethyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(113) 4- (3-phenyloxypropyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(114) 4-Benzyloxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(115) 4- (3-benzyloxypropyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(116) 4- (pyridin-3-ylmethyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(117) 4- (quinolin-2-ylmethyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(118) 4- (pyridin-2-ylmethyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(119) 4- (pyridin-4-ylmethyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(120) 4- (3- (pyridin-3-yl) propyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(121) 4- (3-hydroxypropyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(122) 5-Pentoxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(123) 5- (2-Phenyloxyethyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(124) 5- (3-Hydroxypropyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(125) 5- (pyridin-3-ylmethyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(127) 6- (3-phenyloxypropyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(128) 6-benzyloxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(129) 6-pentoxy-3-phenylthio-2,3-dihydro-1,1-dioxide [
(130) 6- (2- (morpholin-4-yl) ethyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(131) 6- (3-hydroxypropyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(132) 6- (pyridin-3-ylmethyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(133) 6- (3-nitrophenylmethyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(134) 6- (3-bromopropyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(135) 7-pentoxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(136) 7- (2-Phenyloxyethyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(137) 7- (3-hydroxypropyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(138) 7- (pyridin-3-ylmethyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(139) 4- (t-butoxycarbonylmethyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(140) 5- (t-Butoxycarbonylmethyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(141) Synthesis of 6- (t-butoxycarbonylmethyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(142) 7- (t-Butoxycarbonylmethyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(143) Synthesis of 4- (2- (t-butoxycarbonylamino) ethyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(144) 4- (3- (t-butoxycarbonylamino) propyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(145) 5- (2- (t-Butoxycarbonylamino) ethyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(146) 6- (3- (t-butoxycarbonylamino) propyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(147) 6- (2- (t-butoxycarbonylamino) ethyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(148) 7- (2- (t-butoxycarbonylamino) ethyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(149) Synthesis of 4- (N- (t-butoxycarbonyl) piperidin-4-yl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(150) Synthesis of 4,7-bis [(2- (t-butoxycarbonylamino) ethyl) oxy] -3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(151) 4- (3-nitrophenylmethyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(152) 4,7-bis (pyridin-3-ylmethyloxy) -3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(153) 4- (3-hydroxypropyl) oxy-3-phenylsulfinyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(154) 4- (4-nitrophenylmethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(155) 4- (3-phenyloxypropyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(156) 4-Benzyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxo benzo [b] thiophene,
(157) 4- (3-benzyloxypropyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(158) 4- (pyridin-3-ylmethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(159) 4- (N-oxide quinolin-2-ylmethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(160) 4- (pyridin-2-ylmethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(161) 4- (N-oxide pyridin-2-ylmethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(162) 4- (Pyridin-4-ylmethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(163) 4- (3- (pyridin-3-yl) propyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(164) 4- (3-hydroxypropyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(165) 5-Phenoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(166) 5- (2-Phenyloxyethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(167) 5- (3-Hydroxypropyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(168) 5- (pyridin-3-ylmethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(169) 5- (3- (pyridin-3-yl) propyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(170) 6- (3-phenyloxypropyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(171) 6-benzyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(172) 6-pentoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(173) 6- (2- (morpholin-4-yl) ethyl) oxy-3-phenylsulfonyl-2,3-dihydro- 1,1-dioxide benzo [b] thiophene,
(174) 6- (3-Hydroxypropyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(175) 6- (pyridin-3-ylmethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(176) 6- (3-nitrophenylmethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(177) 6- (3-bromopropyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(178) 7-pentoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(179) 7- (2-Phenyloxyethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(180) 7- (3-hydroxypropyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(181) 7- (pyridin-3-ylmethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(182) 7- (N-oxide pyridin-3-ylmethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(183) 4- (t-butoxycarbonylmethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(184) 5- (t-butoxycarbonylmethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(185) 6- (t-Butoxycarbonylmethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(186) 7- (t-butoxycarbonylmethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(187) 4- (2- (t-butoxycarbonylamino) ethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(188) 4- (3- (t- butoxycarbonylamino) propyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(189) 5- (2- (t-butoxycarbonylamino) ethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(190) 6- (3- (t-butoxycarbonylamino) propyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(191) 6- (2- (t-butoxycarbonylamino) ethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(192) 7- (2- (t-butoxycarbonylamino) ethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(193) 4- (N- (t-butoxycarbonyl) piperidin-4-yl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene ,
(194) Synthesis of 4,7-bis [(2- (t-butoxycarbonylamino) ethyl) oxy] -3-phenylsulfonyl-2,3-dihydro- 1,1-dioxide benzo [b] thiophene ,
(195) 4- (3-nitrophenylmethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(196) 4-carboxymethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(197) 5-carboxymethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(198) 6-carboxymethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(199) 7-carboxymethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(200) 4- (N- (pyridin-3-ylmethyl) carbamoylmethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene (200 mg) was added to a solution of 4 - ((2- (N, N- dimethylamino) ethylamino) carbonylmethyl) ,
(202) 4 - ((N-benzyl-2- (N ', N'-dimethylamino) ethylamino) carbonylmethyl) oxy-3-phenylsulfonyl-2,3-dihydro- Benzo [b] thiophene,
(203) 4- (2-aminoethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(204) 4- (3-aminopropyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(205) 5- (2-aminoethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(206) 6- (3-aminopropyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(207) 6- (2-aminoethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(208) 7- (2-aminoethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(209) 4- (Piperidin-4-yl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(210) 4,7-bis [(2-aminoethyl) oxy] -3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(211) 4- (2- (N, N-dimethylamino) ethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(212) 4- (3- (N, N-dimethylamino) propyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(213) 4- (3- (N-Cyanomethyl-N-methylamino) propyl) oxy-3-phenylsulfonyl-2,3-dihydro- 1,1-dioxide benzo [b] thiophene,
(214) 5- (2- (N, N-dimethylamino) ethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(215) 6- (3- (N, N-dimethylamino) propyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(216) 6- (3- (N-Cyanomethyl-N-methylamino) propyl) oxy-3-phenylsulfonyl-2,3-dihydro- 1,1-dioxide benzo [b] thiophene,
(217) 6- (2- (N, N-dimethylamino) ethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(218) 7- (2- (N, N-dimethylamino) ethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(219) 4- (3-aminophenylmethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(220) 4- (3- (pyridin-3-ylcarbonylamino) phenylmethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(221) 4- (2- (Pyridin-3-ylcarbonylamino) ethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(222) 5-Methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(223) 5- (4-chlorophenylcarbonyl) amino-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(224) 4-cyano-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(225) 6-nitro-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(226) 4,7-dimethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(227) 4,7-bis (3-hydroxypropyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(228) 4- (pyridin-3-ylmethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(229) 4- (4-benzylpiperazin-1-yl) carbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(230) 4- (N- (2- (pyridin-3-yl) ethyl) -N-methylcarbamoyl) -3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b ] Thiophene,
(231) 4- (2- (2-hydroxyethoxy) ethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(232) 4- (2,4-dimethoxyphenylmethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(233) 4- (1-Benzylpiperidin-4-yl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(234) 4- (pyridin-4-ylmethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(235) 4- (2-t-Butoxycarbonylethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(236) 4- (thiophen-2-ylmethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(237) 4-Benzylcarbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxo benzo [b] thiophene,
(238) 4- (pyridin-2-ylmethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(239) 4- (2- (piperidin-1-yl) ethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(240) 4 - ((1S) -1-t-butoxycarbonyl-2-methylpropyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro- Thiophene,
(241) 4- (2-fluorophenylmethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(242) 4- (3-fluorophenylmethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(243) 4- (3-methylphenylmethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(244) 4- (2-methoxyphenylmethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(245) 4- (2,3-dimethoxyphenylmethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(246) 4- (3,4-dimethoxyphenylmethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(247) 4- (2,5-difluorophenylmethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(248) 4- (3,4,5-trimethoxyphenylmethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(249) 4- (Benzimidazol-2-ylmethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(250) 4- (3,5-Difluorophenylmethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(251) 4- (N-benzyl-N-methylcarbamoyl) -3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(252) 4- (4-nitrophenylmethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(253) 5- (2-hydroxyethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(254) 5- (Pyridin-3-ylmethyl) carbamoyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(255) 5- (2-Dimethylaminoethyl) carbamoyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(256) 5-Dimethylcarbamoyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(257) 5- (2,3,4,5,6,7-Hexahydro-1H-azepin-1-yl) carbonyl-4-methoxy-3-phenylsulfonyl-2,3- -1,1-dioxide benzo [b] thiophene,
(258) 5- (2,3-Dihydroindol-1-yl) carbonyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro- ,
(259) 5- (4- (2-Chlorophenyl) piperazin-1-yl) carbonyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b ] Thiophene,
(260) 5- (4- (2- (2-Trifluoromethylphenyl) ethyl) piperazin-1-yl) carbonyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro- , 1-dioxide benzo [b] thiophene,
(261) 4- (pyridin-3-ylcarbonyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(262) Synthesis of 4- (3- (pyrrol-1-yl) propyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(263) 4- (Quinolin-2-ylmethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(264) 4- (2- (pyrrol-1-yl) ethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(265) 4- (2- (4-methylthiazol-5-yl) ethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(266) 4- (3- (pyridin-4-yl) propyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(267) 4- (1-t-butoxycarbonylpiperidin-3-ylmethyl) oxy-3-phenylsulfonyl-2,3-dihydro-
(268) 4- (2- (Pyrrolidin-1-yl) ethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(269) 4- (2- (piperidin-1-yl) ethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(270) 4- (2- (2-acetyloxyethoxy) ethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(271) 4- (2- (4-benzylpiperazin-1-yl) ethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(272) 4-Diethylcarbamoylmethyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(273) 4-Cyanomethyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide [
(274) 5- (Pyridin-3-yloxy) methyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(275) 5- (2- (t-butoxycarbonylamino) ethyl) oxy-4-nitro-3-phenylsulfonyl-2,3-dihydro-
(276) 5 - ((2E) -3-ethoxycarbonyl-2-propenyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(277) 4- (2,4-dimethoxyphenylmethyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(278) 4- (pyridin-3-ylmethyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(279) 4- (2-Dimethylaminoethyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(280) 4- (N, N-bis (2-hydroxyethyl) amino) methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(281) 4- (2- (2-hydroxyethoxy) ethyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(282) 4- (4-benzylpiperazin-1-yl) methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
Yl) methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(284) 4- (4-ethoxycarbonylpiperazin-1-yl) methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
Yl) methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
Yl) methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(287) 4-benzylaminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(288) 4- (1-Benzylpiperidin-4-yl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(289) 4- (morpholin-4-yl) methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(290) 4-ethoxycarbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(291) 4-Benzyloxycarbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxo benzo [b] thiophene,
(292) 4- (pyridin-3-yl) -3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(293) 6- (Pyridin-3-yl) -3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(294) 4- (4,4-Dimethyl-4,5-dihydrooxazol-2-yl) -3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene ,
(295) 6-bromo-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(296) 6-Amino-3-phenylsulfonyl-2,3-dihydro-1,1-dioxo [
(297) 5-Methylcarbamoyl-4-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(298) 4-dimethylcarbamoyl-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(299) 4-Carbamoyl-3-phenylthio-2,3-dihydro-1,1-dioxa benzo [b] thiophene,
(300) 4- (2- (pyridin-4-yl) ethyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(301) 4- (2- (pyridin-3-yl) ethyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(302) 4-ethoxycarbonylmethyloxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(303) 6-Ethoxycarbonylmethyloxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(304) 6-Cyanomethyloxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(305) 5-Ethoxycarbonylmethyloxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(306) 7-Ethoxycarbonylmethyloxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(307) 5-Benzyloxycarbonyl-4-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(308) 5-Ethoxycarbonyl-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(309) 7-Methoxycarbonyl-3-phenylthio-2,3-dihydro-1,1-dioxa benzo [b] thiophene,
(310) 7-Ethoxycarbonyl-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(311) 5-t-Butoxycarbonyl-4-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(312) 5- (2- (ethoxycarbonyl) ethyl) -4-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(313) 4- (furan-2-ylmethyl) carbamoyl-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(314) 5- (4,4-dimethyl-4,5-dihydrooxazol-2-yl) -3-phenylthio-2,3-dihydro-
(315) 3-benzylthio-2,3-dihydro-1, 1-dioxide benzo [b] thiophene,
(316) 3- (3,4-dichlorophenyl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(317) 3- (4-nitrophenyl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(318) 5-hydroxymethyl-4-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(319) 4-hydroxymethyl-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(320) 6-Fluoro-3-phenylthio-2,3-dihydro-1,1-dioxide [
(321) 4-Fluoro-3-phenylthio-2,3-dihydro-1,1-dioxa benzo [b] thiophene,
(322) 5-Methylcarbamoyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(323) 4-Dimethylcarbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(324) 4-Carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(325) 4- (2- (pyridin-4-yl) ethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(326) 4- (2- (pyridin-3-yl) ethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(327) 4-ethoxycarbonylmethyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(328) 6-Ethoxycarbonylmethyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(329) 6-Cyanomethyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxo benzo [b] thiophene,
(330) 5-Ethoxycarbonylmethyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(331) 7-Ethoxycarbonylmethyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(332) 5-Benzyloxycarbonyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(333) 5-Ethoxycarbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(334) 7-Methoxycarbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(335) 7-Ethoxycarbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(336) 5-t-Butoxycarbonyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(337) 5- (2-ethoxycarbonylethyl) -4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(338) 3-Benzylsulfonyl-2,3-dihydro-1, 1-dioxide [
(339) 3- (3,4-Dichlorophenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(340) 3- (4-nitrophenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(341) 5-hydroxymethyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(342) 4-hydroxymethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(343) 6-Fluoro-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide [
(344) 4-Fluoro-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide [
(345) 5-benzyloxycarbonyl-4-ethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(346) 5-Benzyloxycarbonyl-4-hexyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(347) 5-benzyloxycarbonyl-4-butoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(348) 5-benzyloxycarbonyl-4-octyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(349) 5-Carboxy-4-ethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(350) 5-Carboxy-4-hexyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(351) 5-carboxy-4-butoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(352) 5-carboxy-4-octyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(353) 5-Methoxycarbonyl-4-ethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(354) 5-Methoxycarbonyl-4-hexyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(355) 5-Methoxycarbonyl-4-butoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(356) 5-Methoxycarbonyl-4-octyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(357) 5- (4- (2- (2-Trifluoromethylphenyl) ethyl) piperazin-1 -yl) carbonyl-4-ethoxy-3-phenylsulfonyl-2,3-dihydro- , 1-dioxide benzo [b] thiophene,
(358) 5- (4- (2-Chlorophenyl) piperazin-1-yl) carbonyl-4-ethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b ] Thiophene,
(359) 5- (2-Dimethylaminoethyl) carbamoyl-4-ethoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(360) 5- (2,3,4,5,6,7-Hexahydro-1H-azepin-1-yl) carbonyl-4-ethoxy-3-phenylsulfonyl-2,3- -1,1-dioxide benzo [b] thiophene,
(361) 5- (2,3-Dihydroindol-1-yl) carbonyl-4-ethoxy-3-phenylsulfonyl-2,3-dihydro- ,
(362) 5- (4- (2- (2-Trifluoromethylphenyl) ethyl) piperazin-1-yl) carbonyl-4-hexyloxy-3-phenylsulfonyl-2,3- 1,1-dioxide benzo [b] thiophene,
(363) 5- (4- (2-Chlorophenyl) piperazin-1-yl) carbonyl-4-hexyloxy-3-phenylsulfonyl-2,3-dihydro- b] thiophene,
(364) 5- (2-Dimethylaminoethyl) carbamoyl-4-hexyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(365) 5- (2,3,4,5,6,7-Hexahydro-1H-azepin-1-yl) carbonyl-4-hexyloxy- Hydro-1,1-dioxide benzo [b] thiophene,
(366) 5- (2,3-Dihydroindol-1-yl) carbonyl-4-hexyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thi Oppen,
(367) 5- (4- (2- (2-Trifluoromethylphenyl) ethyl) piperazin-1-yl) carbonyl-4-butoxy-3-phenylsulfonyl-2,3-dihydro- , 1-dioxide benzo [b] thiophene,
(368) 5- (4- (2-Chlorophenyl) piperazin-1-yl) carbonyl-4-butoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b ] Thiophene,
(369) 5- (2-Dimethylaminoethyl) carbamoyl-4-butoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(370) 5- (2,3,4,5,6,7-Hexahydro-1H-azepin-1 -yl) carbonyl-4-butoxy-3-phenylsulfonyl-2,3- -1,1-dioxide benzo [b] thiophene,
(371) 5- (2,3-Dihydroindol-1-yl) carbonyl-4-butoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene ,
(372) 5- (4- (2- (2-Trifluoromethylphenyl) ethyl) piperazin-1-yl) carbonyl-4-octyloxy-3-phenylsulfonyl-2,3-dihydro- , 1-dioxide benzo [b] thiophene,
(373) 5- (4- (2-Chlorophenyl) piperazin-1-yl) carbonyl-4-octyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b ] Thiophene,
(374) 5- (2-Dimethylaminoethyl) carbamoyl-4-octyloxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(375) 5- (2,3,4,5,6,7-Hexahydro-1H-azepin-1-yl) carbonyl-4-octyloxy-3-phenylsulfonyl-2,3- -1,1-dioxide benzo [b] thiophene,
(376) 5- (2,3-Dihydroindol-1-yl) carbonyl-4-octyloxy-3-phenylsulfonyl-2,3-dihydro- ,
(377) 5-benzyloxy-4-hydroxymethyl-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(378) 5-Benzyloxy-4-bromomethyl-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(379) 5-Benzyloxy-4-aminomethyl-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(380) 5-benzyloxy-4-t-butoxycarbonylaminomethyl-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(381) 5-Benzyloxy-4-t-butoxycarbonylaminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(382) 5-benzyloxy-4-aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(383) 5-hydroxy-4-t-butoxycarbonylaminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(384) 5-Methoxy-4-t-butoxycarbonylaminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(385) 5- (3-phenylpropyl) oxy-4-t-butoxycarbonylaminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(386) 5-Methoxy-4-aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(387) 5- (3-phenylpropyl) oxy-4-aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(388) 5-benzyloxy-4-hydroxymethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(389) 5-benzyloxy-4-carboxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(390) 5-Benzyloxy-4- (pyridin-3-ylmethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(391) 5-Hydroxy-4- (pyridin-3-ylmethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(392) 4,7-dimethoxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(393) 6-bromo-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(394) 4- (Piperidin-3-ylmethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(395) 5- (2-aminoethyl) oxy-4-nitro-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(396) 4- (2- (2-hydroxyethoxy) ethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(397) 5-Carboxy-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(398) 4-Carboxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(399) 4-formyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(400) 5- (4-Phenylbutyl) aminomethyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(401) 5- (Pyridin-3-ylmethyl) aminomethyl-4-methoxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(402) 6-Dimethylamino-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(403) 4- (2-dimethylaminoethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(404) 4,7-bis (pyridin-3-ylmethyloxy) -3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(405) 4- (N-oxide pyridin-3-ylmethyl) oxy-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(406) 4- (2- (N-oxide pyridin-4-yl) ethyl) oxy-3-phenylsulfonyl-2,3-dihydro-
(407) 4-Methoxy-3- (4-hydroxyphenyl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(408) 4-methoxy-3- (4- (pyridin-3-ylmethyloxy) phenyl) thio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(409) 4-methoxy-3- (4- (pyridin-3-ylmethyloxy) phenyl) sulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(410) 5- (2-Dimethylaminoethyl) carbamoyl-4-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(411) 5- (Pyridin-3-ylmethyl) carbamoyl-4-methoxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(412) 4-2- (piperidin-1-yl) ethyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(413) 4- (furan-2-ylmethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(414) 4- (2,4,6-trimethoxybenzyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(415) 4- (3- (2-oxopyrrolidin- 1 -yl) propyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene ,
(416) 4 - ((3S) -1-Benzylpyrrolidin-3-yl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-
(417) 4- (2- (Pyrrolidin-1-yl) ethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(418) 4- (2-diethylaminoethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(419) 4- (2- (N-ethyl-N- (3-methylphenyl) amino) ethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro- Thiophene,
(420) 4- (N-ethyl-N-2- (piperidin-1-yl) ethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b ] Thiophene,
(421) 4- (3- (Imidazol-1-yl) propyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(422) 4 - ((3R) -1-benzylpyrrolidin-3-yl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-
(423) 4- (3- (pyrrolidin-1-yl) propyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(424) 4- (N-2- (Piperidin-1-yl) ethyl-N-methyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b ] Thiophene,
(425) 4- (3,5-dimethoxybenzyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(426) 4- (3- (piperidin-1-yl) propyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(427) 4- (2-Diisopropylamino) ethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(428) 4- (2- (morpholin-4-yl) ethyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(429) 4- (N-2- (Piperidin-1-yl) ethyl-N-propyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b ] Thiophene,
(430) 4- (N-2- (Piperidin-1-yl) ethyl-N-isopropyl) carbamoyl-3-phenylsulfonyl-2,3-dihydro- b] thiophene,
(431) 4- (4-benzoylpiperazin-1-yl) carbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(432) 4- (4- (4-ethylbenzyl) piperazin-1-yl) carbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(433) 4- (4- (4-phenylbenzyl) piperazin-1-yl) carbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(434) 4- (4- (1, 3-dioxaindan-5-ylmethyl) piperazin-1-yl) carbonyl-3-phenylsulfonyl-2,3-dihydro- Benzo [b] thiophene,
(435) 4- (4-Benzyloxycarbonylpiperazin-1-yl) carbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(436) 4- (4- (2-methylphenyl) piperazin-1-yl) carbonyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(437) 4- (4- (4-methoxyphenyl) piperazin-1-yl) carbonyl-3-phenylsulfonyl-2,3-dihydro-
(438) 4- (2- (pyridin-2-yl) ethyl) oxy-3-phenylthio- 1, 1-dioxide benzo [b] thiophene,
(439) 4- (2- (piperidin-1-yl) ethyl) carbamoyl-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(440) 4- (2- (Piperidin-l-yl) ethyl) carbamoyl-3- (4- nitrophenyl) sulfonyl-2,3-dihydro- Thiophene,
Methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene- Thiophene,
(442) 4- (2- (N-ethyl-N-3-methylphenyl) aminoethyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-
(443) 4- (N-benzyl-N-ethyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(444) 4- (2-diethylaminoethyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(445) 4- (4-methylbenzyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(446) 4- (N-Ethyl-N-2- (piperidin-1-yl) ethyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro- Thiophene,
(447) 4- (2-methoxybenzyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(448) 4- (3-phenylpropyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide-benzo [
(449) 4- (3,5-dimethoxybenzyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(452) 4- (2-phenylethyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(453) 4- (N-benzyl-N-methyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(454) 4- (3- (2-oxopyrrolidin- 1 -yl) propyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro- 1,1-dioxide benzo [b] thiophene,
(455) 4- (4-aminobenzyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(456) 4- (4 - ((2E) -3-phenyl-2-propenyl) piperazin- 1 -yl) methyl-3-phenylsulfonyl-2,3-dihydro- [b] thiophene,
(457) 4- (2-aminobenzyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(458) 4- (4-Benzylpiperidin-1-yl) methyl-3-phenylsulfonyl-2,3-dihydro- 1, 1-dioxide benzo [b] thiophene,
(459) 4- (4-chlorobenzyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(460) 4- (3-chlorobenzyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(461) 4- (3-methoxybenzyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(462) 4- (3,4-Dichlorobenzyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(463) 4- (1,3-dioxaindan-5-ylmethyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(464) 4- (2,3-dimethoxybenzyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(465) 4- (3,4,5-trimethoxybenzyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(466) 4- (4- (t-Butyloxycarbonyl) piperazin-1-yl) methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(467) 4- (2-Diisopropylamino) ethyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(468) 4- (2- (Morpholin-4-yl) ethyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro- 1,1-dioxide benzo [b] thiophene,
(469) 4- (N-2- (Piperidin-1-yl) ethyl-N-propyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro- Thiophene,
(470) 4- (N-2- (Piperidin-1-yl) ethyl-N-isopropyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b ] Thiophene,
(471) 4- (3,4-dimethoxybenzyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(472) 4- (3- (2-Methylpiperidin-1-yl) propyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro- 1,1-dioxide benzo [b] thiophene,
Yl) methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene (473) Oppen,
(474) 4- (3- (piperidin-1-yl) propyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(475) 4- (3-bromobenzyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(476) 4- (4-nitrobenzyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(477) 4- (4-aminosulfonylbenzyl) aminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(478) 4- (piperazin-1-yl) methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(479) 4- (2,4,6-trimethoxybenzyl) methyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(480) 4- (Piperidin-1-yl) carbonylmethylaminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(481) 4- (Pyrrolidin-1-yl) ethylaminomethyl-3-phenylsulfonyl-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(482) 4- (4- (1,3-dioxaindan-5-ylmethyl) piperazin-1-yl) methyl-1,1-dioxide benzo [b] thiophene,
An N-oxide derivative thereof, or a non-toxic salt thereof.
[14" claim-type="Currently amended] 5. The compound according to claim 4, wherein the compound is
(1) 4- (pyridin-3-ylmethyl) carbamoyl-1,1-dioxide benzo [b] thiophene,
(2) 4- (4-Benzylpiperazin-1-yl) carbonyl-1,1-dioxide benzo [b] thiophene,
(3) Synthesis of 4- (N- (2- (pyridin-3-yl) ethyl) -N-methylcarbamoyl) -1,1-dioxide benzo [b] thiophene,
(4) 4- (2- (2-hydroxyethoxy) ethyl) carbamoyl-1,1-dioxide benzo [b] thiophene,
(5) 4- (2,4-dimethoxyphenylmethyl) carbamoyl-1,1-dioxide benzo [b] thiophene,
(6) 4- (1-Benzylpiperidin-4-yl) carbamoyl-1, 1-dioxide benzo [b] thiophene,
(7) 4- (Pyridin-4-ylmethyl) carbamoyl-1, 1-dioxide benzo [b] thiophene,
(8) Synthesis of 4- (2-t-butoxycarbonylethyl) carbamoyl-1,1-dioxide benzo [b] thiophene,
(9) 4- (thiophen-2-ylmethyl) carbamoyl-l, l-dioxide benzo [b] thiophene,
(10) 4-Benzylcarbamoyl-1,1-dioxide [0157] Benzo [b] thiophene,
(11) 4- (pyridin-2-ylmethyl) carbamoyl-l, l-dioxide benzo [b] thiophene,
(12) 4- (2- (Piperidin-1-yl) ethyl) carbamoyl-1,1-dioxide benzo [b] thiophene,
(13) 4- ((1S) -1-t-butoxycarbonyl-2-methylpropyl) carbamoyl-1,1-dioxide benzo [b] thiophene,
(14) 4- (2-fluorophenylmethyl) carbamoyl-1, 1-dioxide benzo [b] thiophene,
(15) 4- (3-Fluorophenylmethyl) carbamoyl-l, l-dioxo [b] thiophene,
(16) 4- (3-methylphenylmethyl) carbamoyl-l, l-dioxide benzo [b] thiophene,
(17) 4- (2-methoxyphenylmethyl) carbamoyl-1, 1-dioxide benzo [b] thiophene,
(18) 4- (2,3-Dimethoxyphenylmethyl) carbamoyl-1,1-dioxide benzo [b] thiophene,
(19) 4- (3,4-dimethoxyphenylmethyl) carbamoyl-1,1-dioxide benzo [b] thiophene,
(20) 4- (2,5-difluorophenylmethyl) carbamoyl-1,1-dioxide benzo [b] thiophene,
(21) 4- (3,4,5-trimethoxyphenylmethyl) carbamoyl-1,1-dioxide benzo [b] thiophene,
(22) 4- (Benzimidazol-2-ylmethyl) carbamoyl-l, l-dioxide benzo [b] thiophene,
(23) 4- (3,5-Difluorophenylmethyl) carbamoyl-1,1-dioxo [b] thiophene,
(24) 4- (N-benzyl-N-methylcarbamoyl) -1,1-dioxo [b] thiophene,
(25) 4- (4-nitrophenylmethyl) carbamoyl-1,1-dioxide benzo [b] thiophene,
(26) 5- (2-hydroxyethyl) carbamoyl-1,1-dioxide benzo [b] thiophene,
(27) 5- (Pyridin-3-ylmethyl) carbamoyl-4-methoxy-1,1-dioxide benzo [b] thiophene,
(28) 5- (2-Dimethylaminoethyl) carbamoyl-4-methoxy-1,1-dioxide benzo [b] thiophene,
(29) 5-Dimethylcarbamoyl-4-methoxy-l, l-dioxide benzo [b] thiophene,
(30) 5- (2,3,4,5,6,7-Hexahydro-1H-azepin-1-yl) carbonyl-4-methoxy- 1,1-dioxide benzo [b] thiophene,
(31) 5- (2,3-dihydroindol-1-yl) carbonyl-4-methoxy-1,1-dioxide benzo [b] thiophene,
(32) 5- (4- (2-Chlorophenyl) piperazin-1-yl) carbonyl-4-methoxy- 1,1-dioxide benzo [b] thiophene,
(33) 5- (4- (2- (2-Trifluoromethylphenyl) ethyl) piperazin-1-yl) carbonyl-4-methoxy- 1, 1-dioxide benzo [b] thiophene,
(34) 4- (pyridin-3-ylcarbonyl) aminomethyl-1,1-dioxide benzo [b] thiophene,
(35) 4- (3- (pyrrol-1-yl) propyl) oxy-1,1-dioxide benzo [b] thiophene,
(36) 4- (Quinolin-2-ylmethyl) oxy-1,1-dioxide benzo [b] thiophene,
(37) 4- (2- (pyrrol-1-yl) ethyl) oxy-1,1-dioxide benzo [b] thiophene,
(38) 4- (2- (4-methylthiazol-5-yl) ethyl) oxy-1,1-dioxide benzo [b] thiophene,
(39) 4- (3- (pyridin-4-yl) propyl) oxy-1,1-dioxide benzo [b] thiophene,
(40) 4- (1-t-Butoxycarbonylpiperidin-3-ylmethyl) oxy-1,1-dioxide benzo [b] thiophene,
(41) 4- (2- (Pyrrolidin-1-yl) ethyl) oxy-1,1-dioxide benzo [b] thiophene,
(42) 4- (2- (Piperidin-1-yl) ethyl) oxy-1,1-dioxide benzo [b] thiophene,
(43) 4- (2- (2-Acetyloxyethoxy) ethyl) oxy-1,1-dioxide benzo [b] thiophene,
(44) 4- (2- (4-benzylpiperazin-1-yl) ethyl) oxy-1,1-dioxide benzo [b] thiophene,
(45) 4-diethylcarbamoylmethyloxy-1,1-dioxide benzo [b] thiophene,
(46) 4-Cyanomethyloxy-1,1-dioxide benzo [b] thiophene,
(47) 5- (Pyridin-3-yloxy) methyl-4-methoxy-1,1-dioxide benzo [b] thiophene,
(48) Synthesis of 5- (2-t-butoxycarbonylaminoethyl) oxy-4-nitro-1,1-dioxide benzo [b] thiophene,
(49) 5- ((2E) -3-ethoxycarbonyl-2-propenyl) oxy-1,1-dioxide benzo [b] thiophene,
(50) 4- (2,4-dimethoxyphenylmethyl) aminomethyl-1,1-dioxide benzo [b] thiophene,
(51) 4- (pyridin-3-ylmethyl) aminomethyl-1,1-dioxide benzo [b] thiophene,
(52) 4- (2- (dimethylamino) ethyl) aminomethyl-1,1-dioxide benzo [b] thiophene,
(53) 4- (N, N-bis (2-hydroxyethyl) amino) methyl-1,1-dioxide benzo [b] thiophene,
(54) 4- (2- (2-hydroxyethoxy) ethyl) aminomethyl-1,1-dioxide benzo [b] thiophene,
(55) 4- (4-benzylpiperazin-1-yl) methyl-1,1-dioxide benzo [b] thiophene,
(56) 4- (4- (Pyridin-2-yl) piperazin-1-yl) methyl-1,1-dioxide benzo [b] thiophene,
(57) 4- (4-ethoxycarbonylpiperazin-1-yl) methyl-1,1-dioxide benzo [b] thiophene,
(58) 4- (4- (2-hydroxyethyl) piperazin-1-yl) methyl-1,1-dioxide benzo [b] thiophene,
(59) 4- (4- (Pyridin-4-yl) piperazin-1-yl) methyl-1,1-dioxide benzo [b] thiophene,
(60) 4-benzylaminomethyl-l, l-dioxide benzo [b] thiophene,
(61) 4- (1-Benzylpiperidin-4-yl) aminomethyl-1,1-dioxide benzo [b] thiophene,
(62) 4- (morpholin-4-yl) methyl-1,1-dioxide benzo [b] thiophene,
(63) 4-ethoxycarbonyl-1,1-dioxide benzo [b] thiophene,
(64) 4-Benzyloxycarbonyl-l, l-dioxide [0060] Benzo [b] thiophene,
(65) 4- (pyridin-3-yl) -1,1-dioxide benzo [b] thiophene,
(66) 6- (Pyridin-3-yl) -1,1-dioxa benzo [b] thiophene,
(67) Synthesis of 4- (4,4-dimethyl-4,5-dihydrooxazol-2-yl) -1,1-dioxide benzo [b] thiophene,
(68) 5-Methylcarbamoyl-4-methoxy-l, l-dioxide benzo [b] thiophene,
(69) 4-Dimethylcarbamoyl-l, l-dioxide benzo [b] thiophene,
(70) 4-Carbamoyl-1,1-dioxide benzo [b] thiophene,
(71) 4- (furan-2-ylmethyl) carbamoyl-l, l-dioxide benzo [b] thiophene,
(72) 4- (2- (pyridin-4-yl) ethyl) oxy-1,1-dioxide benzo [b] thiophene,
(73) 4- (2- (pyridin-3-yl) ethyl) oxy-1,1-dioxide benzo [b] thiophene,
(74) 4-ethoxycarbonylmethyloxy-1,1-dioxide benzo [b] thiophene,
(75) 6-Ethoxycarbonylmethyloxy-1,1-dioxide benzo [b] thiophene,
(76) 6-Cyanomethyloxy-1,1-dioxide benzo [b] thiophene,
(77) 5-ethoxycarbonylmethyloxy-1,1-dioxide benzo [b] thiophene,
(78) 7-ethoxycarbonylmethyloxy-1,1-dioxide benzo [b] thiophene,
(79) 5-Benzyloxycarbonyl-4-methoxy-1,1-dioxo [b] thiophene,
(80) 5-ethoxycarbonyl-1,1-dioxide benzo [b] thiophene,
(81) 7-methoxycarbonyl-l, l-dioxide benzo [b] thiophene,
(82) 7-ethoxycarbonyl-1,1-dioxide benzo [b] thiophene,
(83) 5-t-Butoxycarbonyl-4-methoxy-1,1-dioxide benzo [b] thiophene,
(84) 5- (2- (ethoxycarbonyl) ethyl) -4-methoxy-1,1-dioxide benzo [b] thiophene,
(85) 5- (4,4-Dimethyl-4,5-dihydrooxazol-2-yl) -1,1-dioxide benzo [b] thiophene,
(86) 5-benzyloxycarbonyl-4-ethoxy-1, 1-dioxide benzo [b] thiophene,
(87) 5-Benzyloxycarbonyl-4-hexyloxy-l, l-dioxide [
(88) 5-Benzyloxycarbonyl-4-butoxy-1,1-dioxo [b] thiophene,
(89) 5-Benzyloxycarbonyl-4-octyloxy-1,1-dioxo [
(90) 5-Benzyloxy-4-hydroxymethyl-l, l-dioxide [
(91) 4- (1,1-dimethyl-2-hydroxyethyl) carbamoyl-1,1-dioxide benzo [b] thiophene,
(92) 4- (2-hydroxyethyl) carbamoyl-1,1-dioxide benzo [b] thiophene,
(93) 4- (4- (2-Hydroxyethyl) piperazin-1-yl) carbonyl-1,1-dioxide benzo [b] thiophene,
(94) 4- (N-methyl-N-methoxycarbamoyl) -1,1-dioxide benzo [b] thiophene,
(95) 4- (4- (thiazol-2-ylsulfamoyl) phenyl) carbamoyl-1,1-dioxide benzo [b] thiophene,
(96) 4 - ((1 R) -1-t-butoxycarbonyl-2-methylpropyl) carbamoyl-1,1-dioxide benzo [b] thiophene,
(97) 6- (1-Benzylpiperidin-4-yl) carbamoyl-4-methoxy-1,1-dioxide benzo [b] thiophene,
(98) 6- (2-Diethylaminoethyl) carbamoyl-4-methoxy-1,1-dioxide benzo [b] thiophene,
(99) 6- (Pyridin-3-ylmethyl) carbamoyl-4-methoxy-1,1-dioxide benzo [b] thiophene,
(100) 5- (6-dimethylaminohexyl) oxycarbonyl-1,1-dioxide benzo [b] thiophene,
(101) 4- (4-t-Butoxycarbonylpiperazin-1-yl) carbonyl-1,1-dioxide benzo [b] thiophene,
(102) 4- (piperazin-1-yl) carbonyl-1,1-dioxide benzo [b] thiophene,
(103) 4- (4- (4-methoxyphenylmethyl) piperazin-1-yl) carbonyl-1,1-dioxide benzo [b] thiophene,
(104) 4- (4- (4-phenylphenylmethyl) piperazin-1-yl) carbonyl-1,1-dioxide benzo [b] thiophene,
(105) Synthesis of 4- (4- (naphthalen-1-ylmethyl) piperazin-1-yl) carbonyl-1,1-dioxide benzo [b] thiophene,
(106) 4- (4- (4-ethylphenylmethyl) piperazin-1-yl) carbonyl-1,1-dioxide benzo [b] thiophene,
(107) 4- (4- (Naphthalen-2-ylcarbonylmethyl) piperazin-1-yl) carbonyl- 1,1-dioxide benzo [b] thiophene,
(108) 4- (4- (Pyridin-2-ylmethyl) piperazin-1-yl) carbonyl-1,1-dioxide benzo [b] thiophene,
(109) 4- (4- (pyridin-3-ylmethyl) piperazin-1-yl) carbonyl-1,1-dioxide benzo [b] thiophene,
(110) 4- (4-benzoylpiperazin-1-yl) carbonyl-1,1-dioxide benzo [b] thiophene,
(111) 4- (4- (furan-2-ylcarbonyl) piperazin-1-yl) carbonyl-1,1-dioxide benzo [b] thiophene,
(112) 4- (4-Benzylcarbonylpiperazin-1-yl) carbonyl-1,1-dioxide benzo [b] thiophene,
(113) 4- (2- (Pyrrolidin-1-yl) ethyl) carbamoyl- 1, 1-dioxide benzo [b] thiophene,
(114) 4- (3- (pyrrolidin-1-yl) propyl) carbamoyl-1,1-dioxide benzo [b] thiophene,
(115) 4- (4- (2-methylphenyl) piperazin-1-yl) carbonyl-1,1-dioxide benzo [b] thiophene,
(116) 4- (4- (3-methylphenyl) piperazin-1-yl) carbonyl-1,1-dioxide benzo [b] thiophene,
(117) 4- (4- (2-fluorophenyl) piperazin-1-yl) carbonyl-1,1-dioxide benzo [b] thiophene,
(118) 4- (4- (4-fluorophenyl) piperazin-1-yl) carbonyl-1,1-dioxide benzo [b] thiophene,
(119) 4- (4- (4-methoxyphenyl) piperazin-1-yl) carbonyl-1,1-dioxide benzo [b] thiophene,
(120) 4- (4- (3-Trifluoromethylphenyl) piperazin-1-yl) carbonyl-1,1-dioxide benzo [b] thiophene,
(121) 4 - ((3R) -1-Benzylpyrrolidin-3-yl) carbamoyl-1,1-dioxide benzo [b] thiophene,
(122) 4 - ((3S) -1-benzylpyrrolidin-3-yl) carbamoyl-1,1-dioxide benzo [b] thiophene,
(123) 5-acetylmethyloxy-1,1-dioxide benzo [b] thiophene,
(124) 5-Cyanomethyloxy-1,1-dioxide benzo [b] thiophene,
(125) 5-t-butoxycarbonylmethyloxy-1,1-dioxide benzo [b] thiophene,
(126) 5- (3- (ethoxycarbonyl) propyl) oxy-1,1-dioxide benzo [b] thiophene,
(127) 5- (4- (ethoxycarbonyl) butyl) oxy-1,1-dioxide benzo [b] thiophene,
(128) 4- (pyridin-3-ylmethyl) oxy-1, 1-dioxide benzo [b] thiophene,
(129) 4- (pyridin-4-ylmethyl) oxy-1,1-dioxide benzo [b] thiophene,
(130) 4- (4-Trifluoromethylphenylmethyl) oxy-3-phenylthio-2,3-dihydro-1,1-dioxide benzo [b] thiophene,
(131) 4- (3,5-dimethylisoxazol-4-ylmethyl) oxy-1,1-dioxide benzo [b] thiophene,
(132) 4- (4-methoxycarbonylphenylmethyl) oxy-1,1-dioxide benzo [b] thiophene,
(133) 4- (benzotriazol-1-ylmethyl) oxy-1,1-dioxide benzo [b] thiophene,
(134) 4- (2,6-dimethylphenyl) carbamoylmethyloxy-1,1-dioxide benzo [b] thiophene,
(135) 4-trimethylsilylmethyloxy-1,1-dioxide benzo [b] thiophene,
(136) 4- (pyridin-2-ylmethyl) oxy-1, 1-dioxide benzo [b] thiophene,
(137) 4- (2- (pyridin-3-ylcarbonyl) aminoethyl) oxy-1,1-dioxide benzo [b] thiophene,
(138) 4- (3- (pyridin-3-yl) propyl) oxy-1,1-dioxide benzo [b] thiophene,
(139) 4- (2- (pyridin-2-yl) ethyl) oxy-1,1-dioxide benzo [b] thiophene,
(140) 4- (1-t-butoxycarbonylpiperidin-4-yl) oxy-1,1-dioxide benzo [b] thiophene,
(141) 4- (5-methyl-1-tritylimidazol-4-ylmethyl) oxy-1,1-dioxide benzo [b] thiophene,
(142) 4- (1,2,4-oxadiazol-3-ylmethyl) oxy-1,1-dioxide benzo [b] thiophene,
(143) 6- (Pyridin-3-ylmethyl) oxy-1, 1-dioxide benzo [b] thiophene,
(144) 6- (3-nitrophenylmethyl) oxy-1, 1-dioxide benzo [b] thiophene,
(145) 6- (3- (t-butoxycarbonylamino) propyl) oxy-1,1-dioxide benzo [b] thiophene,
(146) 7-t-butoxycarbonylmethyloxy-1,1-dioxide benzo [b] thiophene,
(147) 6- (Pyridin-3-yloxy) methyl-4-methoxy-1,1-dioxide benzo [b] thiophene,
(148) 4,7-bis (3-hydroxypropyl) -1,1-dioxide benzo [b] thiophene,
(149) 5-carboxy-4-ethoxy-l, l-dioxide benzo [b] thiophene,
(150) 5-carboxy-4-butoxy-l, l-dioxide benzo [b] thiophene,
(151) 5-carboxy-4-hexyloxy-l, l-dioxide benzo [b] thiophene,
(152) 5-carboxy-4-octyloxy-1,1-dioxide benzo [b] thiophene,
(153) 5-Ethoxycarbonyl-4-hydroxy-1,1-dioxide benzo [b] thiophene,
(154) 5-Ethoxycarbonyl-4-methoxy-1,1-dioxide benzo [b] thiophene,
(155) 5-Isopropyloxycarbonyl-4-methoxy-1,1-dioxide benzo [b] thiophene,
(156) 5- (2-methylpropyl) oxycarbonyl-4-methoxy-1,1-dioxide benzo [b] thiophene,
(157) 6-methoxycarbonyl-4-methoxy-l, l-dioxide benzo [b] thiophene,
(158) 6-methoxymethoxycarbonyl-4-methoxy-l, l-dioxide benzo [b] thiophene,
(159) 4- (N- (pyridin-2-ylmethyl) -N- (1,1-dioxide benzo [b] thiophen- Thiophene,
(160) 4- (pyridin-2-ylmethyl) aminomethyl-1,1-dioxide benzo [b] thiophene,
(161) 4- (N- (2,4-dimethoxyphenylmethyl) -N- (1,1-dioxide benzo [b] thiophen-4- ylmethyl) amino) methyl- b] thiophene,
(162) 5-acetyloxy-4-nitro-1, 1-dioxide benzo [b] thiophene,
(163) 4- (4,5-dihydrooxazol-2-yl) -1,1-dioxide benzo [b] thiophene,
(164) 5- (4,5-Dihydrooxazol-2-yl) -1,1-dioxide benzo [b] thiophene,
(165) 5-carboxymethyloxy-1, 1-dioxide benzo [b] thiophene,
(166) 7-carboxymethyloxy-l, l-dioxide benzo [b] thiophene,
(167) 4 - ((1S) -1-carboxy-2-methylpropyl) carbamoyl-1,1-dioxide benzo [b] thiophene,
(168) 4 - ((1 R) -1-carboxy-2-methylpropyl) carbamoyl-1,1-dioxide benzo [b] thiophene,
(169) 5- (3-carboxypropyl) oxy-1,1-dioxide benzo [b] thiophene,
(170) 5 - ((2E) -3-carboxy-2-propenyl) oxy-1,1-dioxide benzo [b] thiophene,
(171) 4-2- (Piperidin-1-yl) ethyl) aminomethyl-1,1-dioxide benzo [b] thiophene,
(172) 4-t-Butoxycarbonylamino-1, 1-dioxide benzo [b] thiophene,
(173) 4-amino-1,1-dioxide benzo [b] thiophene,
(174) 4- (4-fluorobenzylamino) -1,1-dioxo [b] thiophene,
(175) 4- (pyridin-3-ylcarbonyl) amino-1,1-dioxide benzo [b] thiophene,
(176) 4- (3-chlorobenzoyl) amino-1,1-dioxide benzo [b] thiophene,
(177) 4-Benzylcarbonylamino-1, 1-dioxo [b] thiophene,
(178) 4- (dimethylaminoacetyl) amino-1,1-dioxide benzo [b] thiophene,
(179) 4-acetylamino-1,1-dioxide benzo [b] thiophene,
(180) 4- (3- (2-oxopyrrolidin-1-yl) propyl) carbamoyl-1,1-dioxide benzo [b] thiophene,
(181) 4- (2-diethylaminoethyl) carbamoyl-1,1-dioxide benzo [b] thiophene,
(182) 4- (2- (N-ethyl-N- (3-methylphenyl) amino) ethyl) carbamoyl-1,1-dioxide benzo [b] thiophene,
(183) 4- (2,4,6-trimethoxybenzyl) carbamoyl-1,1-dioxide benzo [b] thiophene,
(184) 4- (4- (2-hydroxyethyl) piperazin-1-yl) carbonyl-1,1-dioxide benzo [b] thiophene,
(185) 4- (4-Benzyloxycarbonylpiperazin-1-yl) carbonyl-1,1-dioxide benzo [b] thiophene,
(186) 4- (N-ethyl-N-2- (piperidin-1-yl) ethyl) carbamoyl-1,1-dioxide benzo [b] thiophene,
(187) 4- (3- (Imidazol-1-yl) propyl) carbamoyl-1,1-dioxide benzo [b] thiophene,
(188) 4- (N-2- (piperidin-1-yl) ethyl-N-methyl) carbamoyl-1,1-dioxide benzo [b] thiophene,
(189) 4- (4- (1,3-dioxaindan-5-ylmethyl) piperazin-1-yl) carbonyl-1,1-dioxide benzo [b] thiophene,
(190) 4- (4 - ((2E) -3-phenyl-2-propenyl) piperazin- 1 -yl) carbonyl- 1, 1-dioxide benzo [b] thiophene,
An N-oxide derivative thereof, or a non-toxic salt thereof.
[15" claim-type="Currently amended] A pharmaceutical composition comprising the condensed thiophene derivative represented by the formula (IA), the N-oxide derivative thereof or the non-toxic salt thereof as an active ingredient.
[16" claim-type="Currently amended] Treating a compound represented by the formula (XII) to obtain a compound represented by the formula (XIII), treating it with a dehydrogenation reaction to obtain a compound represented by the formula (XIV), and subsequently treating the compound represented by the formula Lt; RTI ID = 0.0 &gt; (XI) &lt; / RTI &gt;
XII

XIII

XIV

XI