Piperazine-substituted benzothiophene derivatives as antipsychotic agents

专利摘要:

公开号:ES2572934T9
申请号:ES12766485.2T
申请日:2012-09-07
公开日:2017-05-08
发明作者:Hiroshi Yamashita；Yohji Sakurai；Motoyuki Miyamoto；Yuichi Nakamura；Hideaki Kuroda；Takuya MINOWA
申请人:Otsuka Pharmaceutical Co Ltd；
IPC主号:

专利说明:

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carbon of 1-6), which has 1-5, preferably 1-3, amino groups. Specific examples of the lower aminoalkyl group include an aminomethyl, diaminomethyl, triaminomethyl, 1-aminoethyl, 2-aminoethyl, 1aminopropyl, 2-aminopropyl, 3-aminopropyl, 4-aminobutyl, 5-aminopentyl, 6-aminohexyl, 1-amino- group 2-methyl ethyl, 1-aminobutyl, 1-amino-2-methylpropyl, 1-amino-2,2-dimethyl ethyl, 1-amino-2-methylbutyl, 1-amino-3-methylbutyl, 1-aminohexyl, 1-amino-2-methylpentyl and Similar.
As for the lower phenylalkyl group, the lower alkyl group mentioned above may be mentioned, which has 1-3, preferably 1, phenyl group. This may be substituted with a lower alkyl group in the phenyl group. Specific examples of the lower phenylalkyl group include a benzyl, 2-phenylethyl, 1-phenylethyl, 3-phenylpropyl, 4-phenylbutyl, 1,1-dimethyl-2-phenylethyl, 5-phenylpentyl, 6-phenylhexyl, 2-methyl-3- group phenylpropyl, diphenylmethyl, 2,2-diphenylethyl and the like.
As for the lower furyl alkyl group, the lower alkyl group mentioned above may be mentioned, which has 1-3, preferably 1, furyl group. This may be substituted with a lower alkyl group in the furyl group. Specific examples of the lower furyl alkyl group include a (2-furyl) methyl, 2- (3-furyl) ethyl, 1- (2-furyl) ethyl, 3- (3-furyl) propyl, 4- (2-furyl) group ) butyl, 5- (3-furyl) pentyl, 6- (2-furyl) hexyl, 1,1-dimethyl-2- (3-furyl) ethyl, 2-methyl-3- (2-furyl) propyl and the like .
As for the lower pyridyl alkyl group, the lower alkyl group mentioned above may be mentioned, which has 1-3, preferably 1, pyridyl group. This may be substituted with a lower alkyl group in the pyridyl group. Specific examples of the lower pyridyl alkyl group include a (4-pyridyl) methyl, 1- (3-pyridyl) ethyl, 2 (2-pyridyl) ethyl, 3- (2-pyridyl) propyl, 4- (3-pyridyl) group butyl, 5- (4-pyridyl) pentyl, 6- (2-pyridyl) hexyl, 1,1-dimethyl-2- (3-pyridyl) ethyl, 2-methyl-3- (4-pyridyl) propyl and the like.
As for the lower alkyl (lower) alkoxy group, the above mentioned lower alkyl group (preferably a straight chain or branched chain alkyl group having a number of carbon atoms of 1-6), having 1 - 3, preferably 1, lower alkoxy group (preferably a straight chain or branched chain alkoxy group having a number of carbon atoms of 1-6) mentioned above. Specific examples of the lower alkoxy (lower) alkyl group include a methoxymethyl, ethoxymethyl, propoxymethyl, hexyloxymethyl, methoxyethyl, ethoxyethyl, propoxyethyl, isopropoxymethyl, butoxymethyl, methyl tert-butoxy, pentyloxymethyl, hexyloxymethyl group and the like.
As for the lower alkoxycarbonyl group, there can be mentioned a straight chain or branched chain alkoxycarbonyl group having a number of carbon atoms of 1-6, wherein the alkoxy radical is the lower alkoxy group mentioned above. More specific examples thereof include a methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, sec-butoxycarbonyl, n-pentyloxycarbonyl, neopentyloxy, n-hexyloxycarbonyloxycarbonyloxycarbonyloxycarbonyl group.
As for the lower alkyl alkyl group, a straight chain or branched chain alkylcarbonyl group having a number of carbon atoms of 1-6 may be mentioned, wherein the lower alkyl radical is the lower alkyl group mentioned above. More specific examples thereof include acetyl, propionyl, butyryl, isobutyryl, valeryl, esovaleryl, pivaloyl and the like.
As for the aminoalkyl (lower) carbonyl group, the alkyl (lower) carbonyl group having 1-5, preferably 1 or 2, amino groups mentioned above may be mentioned. More specific examples thereof include an aminomethylcarbonyl, 2-aminoethylcarbonyl, 1-aminoethylcarbonyl, 3-aminopropylcarbonyl, 4-aminobutylcarbonyl, 5-aminopentylcarbonyl, 6-aminohexylcarbonyl, 1,1-dimethyl-2-aminoethylcarbonyl, 2-methylcarbonyl, and the like group. .
As for the lower (lower) alkoxycarbonylalkyl group, the aforementioned lower alkyl group (preferably a straight chain or branched chain alkyl group having a number of carbon atoms of 1-6), having 1 - can be mentioned 3, preferably 1, lower alkoxycarbonyl group (eg, a methoxycarbonyl, ethoxycarbonyl, n-propoxycarbonyl, isopropoxycarbonyl, n-butoxycarbonyl, isobutoxycarbonyl, tert-butoxycarbonyl, sec-butoxycarbonyl, n-pentyloxycarbonyl, neopexyloxycarbonyl, neopexyloxycarbonyl , isohexyloxycarbonyl, 3-methylpentyloxycarbonyl etc.). Specific examples of the lower (lower) alkoxycarbonylalkyl group include a methoxycarbonylmethyl group, an ethoxycarbonylmethyl group, a propoxycarbonylmethyl group, an isopropoxycarbonylmethyl group, a butoxycarbonylmethyl group, an isobutoxycarbonylmethyl group, a sec-butoxycarbonylmethyl group, a butyloxycarbonylmethyl group, a butyloxycarbonylmethyl group, a butyl methoxycarbonylethyl, a 2-ethoxycarbonylethyl group, a 2-propoxycarbonylethyl group, a 3-methoxycarbonylpropyl group, a 3-ethoxycarbonylpropyl group, a 4-methoxycarbonylbutyl group, a 4-ethoxycarbonylbutyl group and the like.
As for the lower alkoxy (lower) alkoxy group, the aforementioned lower alkoxy group (preferably a straight chain or branched chain alkoxy group having a number of
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(one) an alkyl group,
(2) a cycloalkyl group,
(3) a piperidyl group that optionally has 1 or 2 substituents selected from the group that
it consists of a lower alkyl group, 5 (4) a tetrahydropyranyl group,
(5) a lower alkoxycarbonylalkyl group,
(6) a lower alkoxy lower alkoxy lower alkyl group,
(7) a lower aminoalkyl group optionally having an alkyl (lower) carbonyl group, or
(8) the next group 10
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wherein Ac 'is an alkylene group, Y1a is a lower alkylene group and A is a lower alkylene group,
R4a
is
(one) an alkyl group, or
(2) a cycloalkyl group is preferable, more preferably, R2 is the next group
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20 where
Y1a is a lower alkylene group, Y2a is a lower alkylene group,
R3a '
25 is
(one) an alkyl group,
(2) a cycloalkyl group,
(3) a piperidyl group having optionally 1 or 2 substituents selected from the group consisting of a lower alkyl group,
(4) a tetrahydropyranyl group,
(5) a lower alkoxycarbonylalkyl group,
(6) a lower alkoxy lower alkoxy lower alkyl group, or
(7) a lower aminoalkyl group optionally having an alkyl (lower) carbonyl group,
R4a
is
(one) an alkyl group, or
(2) a cycloalkyl group.
The heterocyclic compound represented by the formula (I) is preferably a heterocyclic compound represented by the following formula (II)
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45 wherein each symbol is defined as in the present specification.
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Examples of the aralkylsulfonyloxy group for X1 include a straight chain or branched chain alkanesulfonyloxy group having a number of carbon atoms of 1-6 and substituted with a phenyl group, which optionally has, as a substituent on the phenyl ring, 1 -3 groups selected from the group consisting of a straight chain or branched chain alkyl group having a number of carbon atoms of 1-6, a straight chain or branched chain alkoxy group having a number of atoms of 1-6 carbon, a nitro group and a halogen atom, a straight chain or branched chain alkanesulfonyloxy group having a number of carbon atoms of 1-6 and substituted with a naphthyl group and the like. Specific examples of the alkanesulfonyloxy group substituted with a phenyl group mentioned above include a benzylsulfonyloxy group, 2
10 phenylethylsulfonyloxy, 4-phenylbutyl sulfonyloxy, 4-methylbenzylsulfonyloxy, 2-methylbenzylsulfonyloxy, 4-nitrobenzylsulfonyloxy, 4methoxybenzylsulfonyloxy, 3-chlorobenzylsulfonyloxy and the like. Specific examples of the alkanesulfonyloxy group substituted with a naphthyl group mentioned above include an α-naphthylmethylsulfonyloxy, β-naphthylmethylsulfonyloxy group and the like.
The reaction of a compound represented by the formula (I-a) and a compound represented by the formula (I-b) is carried out without solvent or in an inert solvent, in the presence or absence of an alkaline compound.
Examples of the inert solvent include water; ethers such as dioxane, tetrahydrofuran, diethyl ether, diethylene glycol dimethyl ether, ethylene glycol dimethyl ether and the like; aromatic hydrocarbons such as benzene,
20 toluene, xylene and the like; lower alcohols such as methanol, ethanol, isopropanol and the like; ketones such as acetone, methyl ethyl ketone and the like; polar solvents such as N, N-dimethylformamide (DMF), dimethylsulfoxide (DMSO), hexamethylphosphoric acid triamide, acetonitrile and the like.
As for the alkaline compound, those known can be widely used and, for example, hydroxides of
25 alkali metals such as sodium hydroxide, potassium hydroxide, cesium hydroxide, lithium hydroxide and the like; alkali metal carbonates such as sodium carbonate, potassium carbonate, cesium carbonate, lithium carbonate and the like; alkali metal hydrogen carbonates such as lithium hydrogen carbonate, sodium hydrogen carbonate, potassium hydrogen carbonate and the like; alkali metals such as sodium, potassium and the like; inorganic bases such as sodium amide, sodium hydride, potassium hydride and the like,
30 and alkali metal alcoholates such as sodium methoxide, sodium ethoxide, potassium methoxide, potassium ethoxide and the like; organic bases such as triethylamine, tripropylamine, pyridine, quinoline, piperidine, imidazole, Netyldiisopropylamine, dimethylaminopyridine, trimethylamine, dimethylaniline, N-methylmorpholine, 1,5-diazabicyclo [4,3,0] noneno-5 (DBN), 1,8-diazabicyclo [5,4,0] undecene-7 (DBU), 1,4-diazabicyclo [2,2,2] octane (DABCO) and the like.
A single class of these alkaline compounds is used, or two or more kinds thereof are mixed and used.
The amount of the alkaline compound to be used is generally 0.5-10 times in moles, preferably 0.5-6 times in moles, with respect to the compound of the formula (I-a).
The aforementioned reaction can be performed by adding, as necessary, an alkali metal iodide such as potassium iodide, sodium iodide and the like as a reaction promoter.
The proportion of the compound of the formula (I-a) and the compound of the formula (I-b) to be used in the scheme
Reaction 1 mentioned above is generally at least 0.5 times in moles, preferably about 0.5 to 5 times in moles, of the latter with respect to the first.
The aforementioned reaction is generally carried out at room temperature at 200 ° C, preferably at room temperature at 150 ° C, and is completed in about 1-30 hr.
50 [Reaction Scheme -2]
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Wherein X2 is a hydroxyl group, a halogen atom or a group that causes a substitution reaction similar to that of a halogen atom, and the other symbols are defined as before.


The halogen atom or group that causes a substitution reaction similar to that caused by a halogen atom for X2 is defined as before.
The reaction of a compound represented by the formula (Ic) and a compound represented by the formula (Id) is carried out under reaction conditions similar to those of the reaction of a compound represented by the formula (Ia) and a compound represented by formula (Ib) in reaction scheme 1 mentioned above.
When a compound (I-d) in which X2 is a hydroxyl group is used, the reaction of the compound (I-c) and the compound (I-d) can also be carried out in a suitable solvent, in the presence of a condensing agent.
10 Specific examples of the solvent to be used herein include water; halogenated hydrocarbons such as chloroform, dichloromethane, dichloroethane, carbon tetrachloride and the like; aromatic hydrocarbons such as benzene, toluene, xylene and the like; ethers such as diethyl ether, diisopropyl ether, tetrahydrofuran, dimethoxyethane and the like; esters such as methyl acetate, ethyl acetate, isopropyl acetate and the like;
Alcohols such as methanol, ethanol, isopropanol, propanol, butanol, 3-methoxy-1-butanol, ethylcelllosolve, methylcelllosolve and the like; aprotic polar solvents such as acetonitrile, pyridine, acetone, DMF, DMSO, hexamethylphosphoric acid triamide and the like, and a solvent mixture thereof and the like.
As the condensing agent, a mixture of azocarboxylate such as diethyl azodicarboxylate and the like and a phosphorus compound such as triphenylphosphine and the like, and the like can be mentioned.
The amount of the condensing agent to be used is generally at least an equimolar amount, preferably an amount of equimolar at 2 molar times, with respect to the compound (I-c).
The amount of compound (I-d) to be used is generally at least an equimolar amount, preferably an amount of equimolar at 2 molar times, with respect to the compound (I-c).
This reaction preferably proceeds generally at 0-200 ° C, preferably at approximately 0-150 ° C, and is generally completed in approximately 1-10 hr.
The compound of the formula (Ia) to be used as the starting substance is produced, for example, by the method shown in the following reaction scheme -3, and the compound represented by the formula (Id) is produced, for example, by the method shown in the following reaction scheme -4.
35 [Reaction Scheme -3]
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wherein X3 is a hydroxyl group, a halogen atom or a group that causes a substitution reaction 40 similar to that of a halogen atom, and the other symbols are defined as before.
The halogen atom or group that causes a substitution reaction similar to that caused by a halogen atom for X3 is defined as before.
The reaction of a compound represented by the formula (Ic) and a compound represented by X3-A-X1 is carried out under reaction conditions similar to those of the reaction of a compound represented by the formula (Ic) and a compound represented by formula (Id) in reaction scheme 2 mentioned above.
[Reaction Scheme -4] 50
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Similar.
For the formulation of a suppository, several conventionally known as carriers in this field can be widely used. Examples thereof include polyethylene glycol, cocoa butter, alcohols, higher esters of higher alcohols, gelatin, semi-synthetic glycerides and the like.
A capsule is prepared by a conventional method generally by mixing an active ingredient compound with various carriers mentioned above and loading the mixture into a hard gelatin capsule, a soft capsule and the like.
For the formulation of an injectable, a liquid, an emulsion and a suspension are preferably sterilized and made isotonic to the blood. For its formulation in such form, several conventionally known as diluents in this field can be widely used. Examples thereof include water, ethyl alcohol, macrogol, propylene glycol, polyoxylated isostearyl alcohol, fatty acid esters and polyoxyethylene sorbitan and the like.
In this case, sodium chloride, glucose or glycerol may be contained in a pharmaceutical preparation in an amount sufficient for the preparation of an isotonic solution, or a general solubilizing agent, a buffering agent, a soothing agent and the like can be added additionally. When necessary, a dye, a preservative, a fragrance, an aroma, a sweetening agent and the like and other pharmaceuticals may be contained in the pharmaceutical preparation.
The amount of compound (I) or a salt thereof that will be contained in the pharmaceutical preparation of the present invention is not particularly limited and is appropriately selected from a wide range. This is generally about 1-70% by weight, preferably about 1-30% by weight, of the composition of the preparation.
The method of administration of the pharmaceutical preparation of the present invention is not particularly limited, and for its administration a method suitable for various dosage forms, age, sex and other conditions of the patients, the level of the disease and Similar. For example, tablets, pills, liquids, suspensions, emulsions, granules, and capsules are administered orally. An injectable is administered intravenously alone or in the form of a mixture with a general liquid replacement such as glucose, amino acids and the like. When necessary, it is administered only by intramuscular, intradermal, subcutaneous or intraperitoneal administration. A suppository is administered intrarectally.
When the dose of the pharmaceutical preparation of the present invention is appropriately selected according to its use, age, sex and other conditions of the patients, the level of the disease and the like, the amount of the active ingredient compound is generally about 0.1 -10 mg per day and per 1 kg of body weight. The active ingredient compound in the range of about 1,200 mg is desirably contained in a unit administration preparation form.
Effect of the invention
The compound of the present invention has a partial agonistic effect of the D2 receptor, an antagonistic effect of the 5-HT2A receptor and an inhibitory effect of serotonin uptake (or inhibitory effect of serotonin reuptake).
The partial agonistic effect of the D2 receptor suppresses dopaminergic neurotransmission (DA) when it is enhanced, and accelerates DAergic neurotransmission when it is reduced and therefore has the function of stabilizing DA neurotransmission to a normal state (dopamine system stabilizer). In accordance with this function, an excellent clinical improvement effect is developed on the abnormal neurotransmission levels of DA (potentiation and reduction), for example, improvement effect on positive and negative symptoms, improvement effect on cognitive impairment, effect of improvement on depressive symptoms etc. without causing side effects (see Michio Toru: Clinical Psychiatry, vol. 46, pages 855-864 (2004), Tetsuro Kikuchi and Tsuyoshi Hirose: Brain Science, vol. 25, pages 579-583 (2004), and Harrison, TS and Perry, CM: Drugs 64: 1715-1736, 2004).
The antagonistic effect of the 5-HT2A receptor reduces extrapyramidal side effects, develops superior clinical effects, and is effective, for example, for the improvement of negative symptoms, the improvement of cognitive impairment, the improvement of depressive symptoms, the improvement of insomnia and the like (see Jun Ishigooka and Ken Inada: Japanese Journal of Clinical Psychofarmacology, vol. 4, pages 1653-1664 (2001), Mitsukuni Murasaki: Japanese Journal of Clinical Psychofarmacology, vol. 1, pages 5-22 (1998), Pullar , IA et al .: Eur. J. Pharmacol., 407: 39-46, 2000, and Meltzer, HY et al .: Prog. Neuro-psychopharmacology. Biol. Psychiatry 27: 1159-1172, 2003).
The inhibitory effect of serotonin uptake (or the inhibitory effect of serotonin reuptake) is effective, by
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example, for the improvement of depressive symptoms (see Mitsukuni Murasaki: Japanese Journal of Clinical Psychofarmacology, vol. 1, pages 5-22 (1998)).
The compound of the present invention is excellent in these three effects, or singularly excellent in one or two of these effects.
In addition, some of the compounds of the present invention have an antagonistic effect of the α1 receptor in addition to the aforementioned effects. The antagonistic effect of the α1 receptor is effective in improving positive symptoms of schizophrenia (see Svensson, T. H .: Prog. Neuro-psychopharmacology. Biol. Psychiatry 27: 1145-1158, 2003).
Therefore, the compound of the present invention has a broad spectrum of treatment for, and excellent clinical effect on, schizophrenia and other diseases of the central nervous system.
Accordingly, the compound, the medicament, and the pharmaceutical composition of the present invention are extremely effective for the improvement of various disorders of the central nervous system including schizophrenia, treatment resistant, refractory or chronic schizophrenia, emotional disturbances, psychotic disorders, disorders of the mood, bipolar disorder (eg, bipolar disorder type I and bipolar disorder type II), mania, depression, endogenous depression, major depression, melancholic depression and treatment-resistant depression, dysthymic disorder, cyclothymic disorder, anxiety disorder ( e.g., panic attack, panic disorder, agoraphobia, social phobia, obsessive-compulsive disorder, post-traumatic stress disorder, generalized anxiety disorder, watery stress disorder, etc.), somatomorphic disorder (e.g. ., hysteria, somatization disorder, conversion disorder, pain disorder, hypochondriasis, etc.), trasto No factitious, dissociative disorder, sexual disorder (p. eg, sexual dysfunction, sexual desire disorder, sexual arousal disorder, erectile dysfunction, etc.), eating disorder (eg, anorexia nervosa, bulimia nervosa, etc.), sleep disorder, adjustment disorder, disorder related to substance use (e.g., alcohol abuse, alcohol intoxication and drug addiction, stimulant poisoning, narcotism, etc.), anhedonia (e.g., anhedonia, anhedonia, iatrogenic anhedonia, cause anhedonia psychic or mental, anhedonia associated with depression, anhedonia associated with schizophrenia, etc.), delirium, cognitive impairment, cognitive impairment associated with Alzheimer's disease, Parkinson's disease, and other neurodegenerative diseases, cognitive impairment caused by Alzheimer's disease, Parkinson's and associated neurodegenerative diseases, cognitive impairment in schizophrenia, cognitive impairment caused by treatment-resistant schizophrenia, refractory or chronic, vomiting, motion sickness, obesity, migraine, pain, mental retardation, autistic disorder (autism), Tourette syndrome, tic disorder, attention deficit hyperactivity disorder, behavior disorder, Down syndrome and the like.
On the other hand, the compound of the present invention barely shows side effects and is superior in tolerability and safety.
Likewise, the compound of the present invention has a remarkably higher solubility in oil such as sesame oil and benzyl benzoate, and can be applied in an oily injection. An oily preparation of the compound of the present invention shows a sustainability of the higher blood concentration. Since the compound of the present invention changes, in blood, to a compound (compound (1)) described in patent document 1, the compound of the present invention is also superior in the long-term maintenance of blood concentration of compound (1) having the desired efficacy.
In addition, the compound of the present invention is easily crystallized, has superior performance, and also has superior chemical stability.
In addition, the compound (I) of the present invention can exert effects such as decrease in the amount of administration, improvement of side effects, enhancement of therapeutic efficacy or the like that may not be achieved by conventional treatment by administering at least one or several drugs used clinically selected from the group consisting of (1) mood stabilizers, (2) serotonin reuptake inhibitors, (3) norepinephrine reuptake inhibitors, (4) serotonin reuptake inhibitors and norepinephrine and (5) antidepressants.
The present invention is explained in more detail hereafter by reference to Reference Examples, Examples and Experimental Examples, which should not be considered as limiting.
Reference Example 1
Synthesis of 7- (tert-butyldimethylsilyloxy) -1-hydroxymethyl-3,4-dihydro-1 H -quinolin-2-one
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Table 1
Example Structural Formula image87
159 image88 N-benzyl-N-methylcarbamic acid 7- [4- (4-benzo [b] thiophene-4-ylpiperazin-1-yl) butoxy] -2-oxo3,4-dihydro-2H-quinolin-1-yl methyl ester
160 image89 Nfenetylcarbamic acid 7- [4- (4-benzo [b] thiophene-4-ylpiperazin-1-yl) butoxy] -2-oxo3,4-dihydro-2H-quinolin-1-yl ester
161 image90 (7- {4- [4- (benzo [b] thiophene-4-yl) piperazin-1-yl] butoxy} -2-oxo-3,4-dihydro-2H-quinolin-1yl) methyl N-methoxycarbamate
162 image91 Nalylcarbamic acid 7- [4- (4-benzo [b] thiophene-4-ylpiperazin-1-yl) butoxy] -2-oxo3,4-dihydro-2H-quinolin-1-yl methyl ester
163 image92 Carbonic acid 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo-2H-quinolin-1-yl methyl ester
164 image93 Propyl ester of 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl ester of carbonic acid
165 image94 Propyl ester of 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo-2H-quinolin-1-ylmethyl carbonic acid ester
Example Structural Formula image95
166 image96 Isopropyl ester of 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo-3,4-dihydro-2H-quinolin-1-methyl ester of carbonic acid
167 image97 Isopropyl ester of 7- [4- (4-benzo [b] thiophene-4-ylpiperazin-1-yl) butoxy] -2-oxo-2H-quinolin-1-ylmethyl ester of carbonic acid
168 image98 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo-2H-quinolin-1-ylmethyl ester of carbonic acid
169 image99 Isobutyl ester of 7- [4- (4-benzo [b] thiophene-4-ylpiperazin-1-yl) butoxy] -2-oxo-3,4-dihydro-2H-quinolin-1-methyl ester of carbonic acid
170 image100 Isobutyl ester of 7- [4- (4-benzo [b] thiophene-4-ylpiperazin-1-yl) butoxy] -2-oxo-2H-quinolin-1-ylmethyl ester of carbonic acid
171 image101 Carbonic acid 7- [4- (4-benzo [b] thiophene-4-ylpiperazin-1-yl) butoxy] -2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl ester of carbonic acid
172 image102 Pentyl ester of 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo-2H-quinolin-1-ylmethyl carbonic acid ester
Example Structural Formula image103
173 image104 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo-3,4-dihydro-2H-quinolin-1-methyl ester of carbonic acid ester 3-methylbutyl ester
174 image105 Carbonic acid 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo-2H-quinolin-1-ylmethyl ester of carbonic acid
175 image106 Hexyl ester of 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo-2H-quinolin-1-ylmethyl ester of carbonic acid
176 image107 Carbonic acid 7- [4- (4-benzo [b] thiophene-4-ylpiperazin-1-yl) butoxy] -2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl ester
177 image108 Carbonic acid 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo-2H-quinolin-1-yl methyl ester
178 image109 Tetradecyl ester of 7- [4- (4-benzo [b] thiophene-4-ylpiperazin-1-yl) butoxy] -2-oxo-3,4-dihydro-2H-quinoline-1-methyl ester of carbonic acid
179 image110 Tetradecyl ester of 7- [4- (4-benzo [b] thiophene-4-ylpiperazin-1-yl) butoxy] -2-oxo-2H-quinolin-1-ylmethyl ester of carbonic acid
Example Structural Formula image111
180 image112 Hexadecyl ester of 7- [4- (4-benzo [b] thiophene-4-ylpiperazin-1-yl) butoxy] -2-oxo-2H-quinolin-1-ylmethyl ester of carbonic acid
181 image113 Benzyl ester 7- (4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl carbonic acid
182 image114 Benzyl ester 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo-2H-quinolin-1-ylmethyl carbonic acid
183 image115 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -1-methoxymethyl-3,4-dihydro-1H-quinolin-2-one
184 image116 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -1methoxymethyl-1H-quinolin-2-one
185 image117 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2methoxymethoxyquinoline
186 image118 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -1-ethoxymethyl3,4-dihydro-1H-quinolin-2-one
Example Structural Formula image119
187 image120 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -1-ethoxymethyl1H-quinolin-2-one
188 image121 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -1isopropoxymethyl-3,4-dihydro-1 H-quinolin-2-one
189 image122 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -1isopropoxymethyl-1H-quinolin-2-one
190 image123 Amino acid 7- (4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo3,4-dihydro-2H-quinolin-1-yl-methyl ester
191 image124 Amino acid 7- (4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo2H-quinolin-1-ylmethyl ester of acetic acid
192 image125 Aminopropionic acid 2- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo3,4-dihydro-2H-quinolin-1-yl-methyl ester
193 image126 2-Aminopropionic acid 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2oxo-2H-quinolin-1-ylmethyl ester
Example Structural Formula image127
194 image128 2-Amino-3-methylbutyric acid 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo3,4-dihydro-2H-quinolin-1-yl methyl ester
195 image129 2-Amino-3-methylbutyric acid 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo2H-quinolin-1-ylmethyl ester
196 image130 2-Amino-4-methylpentanoic acid 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo3,4-dihydro-2H-quinolin-1-ylmethyl ester
197 image131 2-Amino-4-methylpentanoic acid 7- [4- (4-benzo [b] thiophene-4-ylpiperazin-1-yl) butoxy] -2-oxo2H-quinolin-1-ylmethyl ester
198 image132 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo3,4-dihydro-2H-quinolin-1-ylmethyl ester of pyrrolidin-2-carboxylic acid
199 image133 Pyrrolidine-2-carboxylic acid 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo2H-quinolin-1-ylmethyl ester
Example Structural Formula image134
200 image135 {7- [4- (4- (Benzo [b] thiophen-4-yl) piperazin-1-yl] butoxy} -2-oxo-3,4-dihydro-2H-quinolin-1-yl) calcium methyl phosphate
201 image136 {7- [4- (4- (Benzo [b] thiophene-4-yl) piperazin-1-yl] butoxy} -2-oxo-2Hquinolin-1-yl) calcium methyl phosphate
202 image137 (7- {4- [4- (Benzo [b] thiophene-4-yl) piperazin-1-yl] butoxy} quinolin-2-yloxy) calcium methyl phosphate
203 image138 Propionic acid ester 7- [4- (4-benzo [b] thiophen-4ylpiperazin-1-yl) butoxy] -2-oxo-3,4-dihydro-2H-quinolin-1-methylmethyl
204 image139 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo3,4-dihydro-2H-quinolin-1-ylmethyl ester of pentanoic acid
205 image140 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo3,4-dihydro-2H-quinolin-1-ylmethyl ester of heptanoic acid
206 image141 Nonanoic acid 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo3,4-dihydro-2H-quinolin-1-ylmethyl ester
Example Structural Formula image142
207 image143 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo3,4-dihydro-2H-quinolin-1-ylmethyl ester of undecanoic acid
208 image144 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo3,4-dihydro-2H-quinolin-1-ylmethyl ester of tridecanoic acid
209 image145 Nonadecanoic acid 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo3,4-dihydro-2H-quinolin-1-ylmethyl ester
210 image146 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo3,4-dihydro-2H-quinolin-1-ylmethyl ester of henicosanoic acid
211 image147 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo3,4-dihydro-2H-quinolin-1-ylmethyl ester of docosanoic acid
212 image148 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo3,4-dihydro-2H-quinolin-1-ylmethyl ester of tricosanoic acid
Example Structural Formula image149
213 image150 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo3,4-dihydro-2H-quinolin-1-ylmethyl ester of tetracosanoic acid
214 image151 2,2-dimethylbutyric acid 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo3,4-dihydro-2H-quinolin-1-yl methyl ester
215 image152 2,2-dimethylpentanoic acid 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo3,4-dihydro-2H-quinolin-1-ylmethyl ester
216 image153 2,2-dimethyldodecanoic acid 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo3,4-dihydro-2H-quinolin-1-yl ester
217 image154 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo3,4-dihydro-2H-quinolin-1-ylmethyl ester of isobutyric acid
218 image155 3-Methylbutyric acid 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo3,4-dihydro-2H-quinolin-1-yl-methyl ester
219 image156 1- {7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2oxo-3,4-dihydro-2H-quinolin-1-yl} ethyl ester of decanoic acid
Example Structural Formula image157
220 image158 Dodecanoic acid 1- {7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2oxo-3,4-dihydro-2H-quinolin-1-yl} ethyl ester
221 image159 1- {7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2oxo-3,4-dihydro-2H-quinolin-1-yl} ethyl ester of tetradecanoic acid
222 image160 Hexadecanoic acid ethyl 1- {7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2oxo-3,4-dihydro-2H-quinolin-1-yl} ethyl ester
223 image161 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo3,4-dihydro-2H-quinolin-1-ylmethyl acid (2-methoxyethoxy) acetic acid ester
224 image162 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo3,4-dihydro-2H-quinolin-1-ylmethyl acid [2- (2-methoxyethoxy) ethoxy acid ester ]acetic
225 image163 Ester (9Z, 12Z) -7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl acid octadeca -9,12-dienoic
226 image164 Ester (9Z, 12Z, 15Z) -7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl octadeca-9,12,15-trienoic acid
Example Structural Formula image165
227 image166 Ester (4Z, 7Z, 10Z, 13Z, 16Z, 19Z) -7- [4- (4-benzo [b] thiophen-4ilpiperazin-1-yl) butoxy] -2-oxo-3,4-dihydro-2H- quinoline-1-methylmethyl acid docosa-4,7,10,13,16,19-hexaenoic
228 image167 Ester (6Z, 9Z, 12Z, 15Z) -7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo-3,4-dihydro-2H-quinolin-1- octadeca-6,9,12,15-tetraenoic acid ilmethyl
229 image168 Esonicotinic acid 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo3,4-dihydro-2H-quinolin-1-yl ester ester
230 image169 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo3,4-dihydro-2H-quinolin-1-ylmethyl ester of pyrimidine-5-carboxylic acid
231 image170 Pyridazine-4-carboxylic acid 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo3,4-dihydro-2H-quinolin-1-ylmethyl ester
232 image171 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo2H-quinolin-1-ylmethyl ester of propionic acid
233 image172 Pentanoic acid 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo2H-quinolin-1-ylmethyl ester
Example Structural Formula image173
2. 3. 4 image174 7- (4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo2H-quinolin-1-ylmethyl ester of heptanoic acid
235 image175 Nonanoic acid 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo2H-quinolin-1-ylmethyl ester
236 image176 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo2H-quinolin-1-ylmethyl ester of undecanoic acid
237 image177 Tridecanoic acid 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo2H-quinolin-1-ylmethyl ester
238 image178 Nonadecanoic acid 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo2H-quinolin-1-ylmethyl ester
239 image179 Henicosanoic acid 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo2H-quinolin-1-ylmethyl ester
240 image180 Docosanoic acid 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo2H-quinolin-1-ylmethyl ester
Example Structural Formula image181
241 image182 Tricosanoic acid 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo2H-quinolin-1-ylmethyl ester
242 image183 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo2H-quinolin-1-ylmethyl tetracosanoic acid ester
243 image184 2,2-Dimethylbutyric acid 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo2H-quinolin-1-ylmethyl ester
244 image185 2,2-Dimethylpentanoic acid 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo2H-quinolin-1-ylmethyl ester
245 image186 2,2-Dimethyldodecanoic acid 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo2H-quinolin-1-ylmethyl ester
246 image187 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo2H-quinolin-1-ylmethyl ester of isobutyric acid
Example Structural Formula image188
247 image189 3-Methylbutyric acid 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo2H-quinolin-1-ylmethyl ester
248 image190 1- {7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2oxo-2H-quinolin-1-yl} ethyl ester of decanoic acid
249 image191 Dodecanoic acid 1- {7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2oxo-2H-quinolin-1-yl} ethyl ester
250 image192 Tetradecanoic acid ethyl 1- {7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2oxo-2H-quinolin-1-yl} ethyl ester
251 image193 Hexadecanoic acid ethyl 1- {7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2oxo-2H-quinolin-1-yl} ethyl ester
252 image194 1-Methylpiperidine-4-carboxylic acid 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo2H-quinolin-1-ylmethyl ester
253 image195 2-Methoxyethoxy acetic acid 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo2H-quinolin-1-ylmethyl ester
Example Structural Formula image196
254 image197 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo2H-quinolin-1-ylmethyl acid [2- (2-methoxyethoxy) ethoxy] acetic acid ester
255 image198 2- (4- Butoxy-ethoxy) acetic acid 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo2H-quinolin-1-ylmethyl ester
256 image199 Ester (9Z, 12Z) -7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo-2H-quinolin-1-ylmethyl acid octadeca9,12-dienoic acid
257 image200 Ester (9Z, 12Z, 15Z) -7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo-2H-quinolin-1-ylmethyl acid octadeca9,12,15 -trienoic
258 image201 Ester (4Z, 7Z, 10Z, 13Z, 16Z, 19Z) -7- [4- (4-benzo [b] thiophen-4ilpiperazin-1-yl) butoxy] -2-oxo-2H-quinolin-1-ylmethyl Docose-4,7,10,13,16,19-hexaenoic acid
259 image202 Ester (6Z, 9Z, 12Z, 15Z) -7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo-2H-quinolin-1-ylmethyl acid octadeca-6 , 9,12,15-tetraenoic
260 image203 Esonicotinic acid 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo2H-quinolin-1-ylmethyl ester
Example Structural Formula image204
261 image205 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo2H-quinolin-1-ylmethyl ester of nicotinic acid
262 image206 Pyrimidine-5-carboxylic acid 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo2H-quinolin-1-ylmethyl ester
263 image207 Pyridazine-4-carboxylic acid 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo2H-quinolin-1-ylmethyl ester
264 image208 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo3,4-dihydro-2H-quinolin-1-ylmethyl ester of pyridine-2-carboxylic acid
265 image209 Pyridin-2-carboxylic acid 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo2H-quinolin-1-ylmethyl ester
266 image210 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo3,4-dihydro-2H-quinolin-1-ylmethyl ester of furan-2-carboxylic acid
Example Structural Formula image211
267 image212 Furan-2-carboxylic acid 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo2H-quinolin-1-ylmethyl ester
268 image213 7- [4- (4-Benzo [b] thiophene-4-ylpiperazin-1-yl) butoxy] -2-oxo3,4-dihydro-2H-quinolin-1-ylmethyl ester of thiophene-3-carboxylic acid
269 image214 Thiophene-3-carboxylic acid 7- [4- (4-benzo [b] thiophene-4-ylpiperazin-1-yl) butoxy] -2-oxo2H-quinolin-1-ylmethyl ester
270 image215 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo3,4-dihydro-2H-quinolin-1-ylmethyl ester of quinolin-6-carboxylic acid
271 image216 Quinolin-6-carboxylic acid 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -2-oxo2H-quinolin-1-ylmethyl ester
272 image217 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl ester of benzoic acid
Example Structural Formula image218
273 image219 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-yl-methyl acid ester , 2-dimethylpropionic
274 image220 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-yl-methyl ester of butyric acid
275 image221 Phenylacetic acid 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl ester
276 image222 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl ester of octanoic acid
277 image223 Cyclohexanecarboxylic acid 7- [4- (4-benzo [b] thiophene-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinoline-1-ylmethyl ester
278 image224 Cyclopentanecarboxylic acid 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-cyclopentanecarboxylic acid ester
Example Structural Formula image225
279 image226 Ester (Z) -7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] 4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1 -ethyldecyl octadec-9-enoic acid
280 image227 Hexadecanoic acid 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl ester
281 image228 Iicosanoic acid 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-yl-methyl ester
282 image229 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-yl-methyl acid ester -pentyl-heptanoic
283 image230 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl acid ester of decanoic acid
284 image231 Hexanoic acid 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl ester
Example Structural Formula image232
285 image233 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl ester of octadecanoic acid
286 image234 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-yl-methyl acetate ester
287 image235 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl ester of propionic acid
288 image236 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl ester of pentanoic acid
289 image237 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-yl-methyl ester of heptanoic acid
290 image238 Nonanoic acid 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl ester
291 image239 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl ester of undecanoic acid
Example Structural Formula image240
 image241 image242 image243
292 image244 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl ester of tridecanoic acid
293 image245 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl ester of tetradecanoic acid
294 image246 Pentadecanoic acid 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl ester
295 image247 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl ester of heptadecanoic acid
296 image248 Nonadecanoic acid 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl ester
Example Structural Formula image249
297 image250 7- [4- (4-Benzo [b] thiophene-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl ester of henicosanoic acid
298 image251 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-yl-methyl ester of docosanoic acid
299 image252 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-yl-methyl ester of tricosanoic acid
300 image253 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl ester of tetracosanoic acid
301 image254 7- [4- (4-Benzo [b] thiophene-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2-quinoline-1-ylmethyl ester tert-butyl ester of malonic acid
302 image255 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-yl-methyl acid ester -methyl-butyric
Example Structural Formula image256
303 image257 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-yl-methyl acid ester -methyl-pentanoic
304 image258 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-yl-methyl acid ester -methyl-hexanoic
305 image259 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-yl-methyl acid ester , 2-dimethyl-hexanoic
306 image260 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-yl-methyl ester of isobutyric acid
307 image261 3- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-yl-methyl acid ester -methyl-butyric
308 image262 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl acid ester -methyl-pentanoic
Example Structural Formula image263
309 image264 Cyclobutanecarboxylic acid 7- [4- (4-benzo [b] thiophene-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinoline-1-yl-methyl ester
310 image265 Ester 1- {7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-yl } -ethyl decanoic acid
311 image266 Ester 1- {7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-yl } -edecanoic acid ethyl
312 image267 Ester 1- {7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-yl } -tetradecanoic acid ethyl
313 image268 Ester 1- {7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-yl } -hexadecanoic acid ethyl
314 image269 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinoline-1-ylmethyl ester of tetrahydro ester -piran-4-carboxylic
Example Structural Formula image270
315 image271 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl acid ester ( 2-methoxy-ethoxy) -acetic
316 image272 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl acid ester [ 2- (2-methoxy-ethoxy) -ethoxy] -acetic
317 image273 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl acid ester ( 2-butoxy-ethoxy) -acetic
318 image274 Cycloheptanecarboxylic acid 7- [4- (4-benzo [b] thiophene-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinoline-1-yl-methyl ester
319 image275 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl acid ester , 4,4-trifluoro-butyric
320 image276 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl ester of piperidin acid -1-carboxylic
321 image277 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl acid ester -butyl-N-methylcarbamic
Example Structural Formula image278
322 image279 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl acid ester , N-dibutylcarbamic
323 image280 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl acid ester -cyclohexylmethylcarbamic
324 image281 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl acid ester -butylcarbamic
325 image282 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl acid ester -methylcarbamic
326 image283 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl acid ester , N-dimethylcarbamic
327 image284 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl acid ester -ethylcarbamic
Example Structural Formula image285
328 image286 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl acid ester , N-diethylcarbamic
329 image287 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl acid ester -pentadecylcarbamic
330 image288 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl acid ester -octadecylcarbamic
331 image289 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl acid ester -methyl-N-octadecylcarbamic
332 image290 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl acid ester -cyclohexylcarbamic
333 image291 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl acid ester -benzylcarbamic
334 image292 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl acid ester -benzyl-N-methylcarbamic
Example Structural Formula image293
335 image294 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl acid ester -fenetylcarbamic
336 image295 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl ester of morpholin acid -4-carboxylic
337 image296 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-d -ethyl-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl ester of N (2-methoxyethyl) carbamic acid
338 image297 {7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-methylmethoxycarbonylamino} methyl ester acetic
339 image298 ({7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2-quinoline-1-ylmethoxycarbonyl acid methyl ester } -methyl-amino) acetic
340 image299 (7- {4- [4- (benzo [b] thiophene-4-yl) piperazin-1-yl] butoxy} -4,4-dimethyl-2-oxo-3,4-dihydro-2-quinoline-1 N-methoxycarbamate -il) methyl
341 image300 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2-quinoline-1-ylmethyl N-benzyloxycarbamate
Example Structural Formula image301
342 image302 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl acid ester - (3,3,3-Trifluoro-propyl) carbamic
343 image303 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl acid ester -furan-2-ylmethylcarbamic
344 image304 7- (4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-methyl methyl ester ester carbonic
3. 4. 5 image305 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-methyl methyl ester carbonic
346 image306 Propyl ester of 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-methyl methyl ester carbonic
347 image307 Isopropyl ester of 7- [4- (4-benzo [b] thiophene-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2-quinoline-1-ylmethyl acid ester carbonic
348 image308 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-methyl ester ester butyl ester carbonic
Example Structural Formula image309
349 image310 Isobutyl ester of 7- [4- (4-benzo [b] thiophene-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2-quinoline-1-ylmethyl acid ester carbonic
350 image311 Pentyl ester of ester 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-methyl ester carbonic
351 image312 7- [4- (4-benzo [b] thiophene-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2-quinoline-1 ester ester 3-methyl-butyl ester -carbonic acid methylmethyl
352 image313 Hexyl ester 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-methyl ester carbonic
353 image314 7- [4- (4-Benzo [b] thiophene-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-methyl methyl ester ester carbonic
354 image315 Tetradecyl ester of 7- [4- (4-benzo [b] thiophene-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2-quinoline-1-yl-methyl ester carbonic
355 image316 Hexadecyl ester of 7- [4- (4-benzo [b] thiophene-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2-quinoline-1-yl-methyl ester carbonic
Example Structural Formula image317
356 image318 Benzyl ester 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-methyl ester carbonic
357 image319 Heptyl ester of ester 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-methyl ester carbonic
358 image320 Oct 7- ester of 7- [4- (4-benzo [b] thiophene-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-methyl methyl ester carbonic
359 image321 2,2,2-Trifluoro-ethyl ester of ester 7- [4- (4-benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro -2Hquinolin-1-carbonic acid ilmethyl
360 image322 Cyclohexyl ester of 7- [4- (4-benzo [b] thiophene-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2-quinoline-1-yl-methyl ester carbonic
361 image323 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -1-methoxymethyl-4,4-dimethyl-3,4-dihydro-1H-quinolin-2-one
Example Structural Formula image324
362 image325 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -1-ethoxymethyl4,4-dimethyl-3,4-dihydro-1H-quinolin-2-one
363 image326 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -1isopropoxymethyl-4,4-dimethyl-3,4-dihydro-1H-quinolin-2-one
364 image327 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -1-benzyloxymethyl-4,4-dimethyl-3,4-dihydro-1H-quinolin-2-one
365 image328 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl1- (2,2,2-trifluoro-ethoxymethyl) -3,4-dihydro-1H -quinolin-2-one
366 image329 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-yl-methyl ester -acetic
367 image330 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-yl-methyl acid ester -amino-propionic
Example Structural Formula image331
368 image332 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-yl-methyl acid ester -amino-3-methyl-butyric
369 image333 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-yl-methyl acid ester -amino-4-methyl-pentanoic
370 image334 7- [4- (4-Benzo [b] thiophen-4-ylpiperazin-1-yl) butoxy] -4,4-dimethyl-2-oxo-3,4-dihydro-2H-quinolin-1-ylmethyl ester of pyrrolidin acid -2-carboxylic
Example 371 Synthesis of 7- [4- (4-benzo [b] thiophen-4-yl-piperazin-1-yl) -butyloxy] -quinolin-2-yloxymethyl dodecanoate
image335
To a solution of 7- [4- (4-benzo [b] thiophen-4-yl-piperazin-1-yl) -butoxy] -1H-quinolin-2-one (800 mg) synthesized in the same manner as in WO2006 / 112464 (Example 1) in dimethylformamide (30 ml) was added
10 silver carbonate (I) (0.76 g), chloromethyldodecanoate [61413-67-0] (1.15 g), and the mixture was stirred at 60 ° C for 6 hr. Water was added to the reaction mixture, and the mixture was extracted with ethyl acetate and dried over Na2SO4. The solvent was evaporated under reduced pressure and the residue was purified by silica gel column chromatography (ethyl acetate: n-hexane = 2: 1) to provide 7- [4- (4-benzo [b] thiophene dodecanoate) -4-yl-piperazin-1-yl) -butyloxy] quinolin-2-yloxymethyl (22 mg).
Oil: colorless H1 NMR (CDCl3) δ ppm: 0.87 (3H, t, J = 7.1 Hz), 1.16-2.10 (18H, m), 2.36 (2H, t, J = 7.5 Hz), 2.58 (2H, t, J = 7.5 Hz), 2.76 (4H, wide), 3.21 (4H, wide), 4.15 (2H, t, J = 6.3 Hz), 6.25 (2H, s), 6.80 (1H, d, J = 8.7 Hz), 6.90 (1H, d, J = 7.4 Hz), 7, 06 (1H, dd, J = 2.5, 8.8 Hz), 7.22 (1H, d, J = 2.3 Hz), Hz), 7.27 (1H, t, J = 7.8 Hz), 7.36-7.44 (2H, m), 7.55 (1H, d, J = 8.0Hz), 7.61 (1H, d, J = 8.8 Hz), 7.96 (1H, d, J = 8.7 Hz)
20 Example 372
Synthesis of 7- [4- (4-benzo [b] thiophen-4-yl-piperazin-1-yl) -butyloxy] -quinolin-2-yloxymethyl cyclohexylcarbonate
image336
image337
image338
image339
image340
image341
Sodium hydride (55% oil) (0.962 g, 22.04 mmol) was suspended in tetrahydrofuran (THF) (200 ml), 7- [4- (4-benzo [b] thiophene-4-yl-] piperazin-1-yl) -butyloxy] -1H-quinolin-2-one (8.31 g, 19.17 mmol) and the mixture was stirred at 50 ° C for 1 hr. The mixture was cooled to 0 ° C, chloromethyl cyclohexylcarbonate (4.80 g, 24.92 mmol) was added dropwise and the mixture was stirred at room temperature overnight. After cooling to 0 ° C, 2N hydrochloric acid was added to quench the reaction. The precipitated solid was collected by filtration and dried. In addition, the filtrate was extracted with ethyl acetate. The organic layer was concentrated and purified by silica gel column chromatography at moderate pressure (methylene chloride: methanol = 100: 0 to 20: 1). Likewise
To form, the solid was purified by silica gel column chromatography at moderate pressure. Concentration under reduced pressure produced the title compound (yield, 5.04 g, 42%) as a white solid. 1 H NMR (DMSO-d6) δ ppm: 1.16 (m, 6H), 1.59-1.69 (m, 2H), 1.80 (m, 6H), 3.00-3.60 (m , 10H), 4.19 (t, J = 5.9 Hz, 2H), 4.57-4.65 (m, 1H), 6.29 (s, 2H), 6.42 (d, J = 9.5 Hz, 1H), 6.97 (dd, J = 2.3, 8.5 Hz, 1H), 6.98 (dd, J = 1.8, 7.7 Hz,
15 1H), 7.04 (d, J = 2.3 Hz, 1H), 7.31 (dd, J = 7.7, 7.7 Hz, 1H), 7.43 (dd, J = 1, 8, 5.5 Hz, 1H), 7.63-7.71 (m, 3H), 7.86 (d, J = 9.5 Hz, 1H).
In the same manner as in the aforementioned Examples, the compounds described in the following Table 2 can be synthesized.
20 (Examples that are not within the scope of the claimed invention are marked in Table 2 with an asterisk (*))
Example Structural Formula image342
386 image343 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxoquinolin-1 (2H) -yl) methyl dipropylcarbamate
387 image344 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxoquinolin-1 (2H) -yl) methyl diisobutylcarbamate
388 image345 (7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -2-oxoquinolin-1 (2H) -yl) methyl dihexylcarbamate
389 image346 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxoquinolin-1 (2H) -yl) methyl nonadecyl carbonate


390 image347 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxoquinolin-1 (2H) -yl) methyl (nonyl) carbamate
391 image348 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxoquinolin-1 (2H) -yl) methyl (tetradecyl) carbamate
392 image349 (7- (4- (4- (benzo [b] hylophene-4-yl) piperazin-1-yl) butoxy) -2-oxoquinolin-1 (2H) -yl) methyl ditetradecylcarbamate
393 image350 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxoquinolin-1 (2H) -yl) methyl dinonylcarbamate
394 image351 2,2-dimethyldecanoate (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxoquinolin-1 (2H) -yl) methyl
395 image352 decanoate 1- (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxoquinolin-1 (2H) -yl) -2-ethoxy-2-oxoethyl
396 image353 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxoquinolin-1 (2H) -yl) methyl 2,2-dimethyloctanoate
397 image354 1- (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxoquinolin-1 (2H) -yl) ethyl butyrate
127
Example Structural Formula image355
398 image356 1- (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxoquinolin-1 (2H) -yl) ethyl 3-methylbutanoate
399 image357 1- (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxoquinolin-1 (2H) -yl) ethyl hexanoate
400 image358 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxoquinolin-1 (2H) -yl) methyl 2-hydroxyethylcarbamate
401 image359 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxoquinolin-1 (2H) -yl) methyl bis (2-hydroxyethyl) carbamate
402 image360 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxoquinolin-1 (2H) -yl) methyl 4-methylpiperazin-1-carboxylate
403 image361 1,4'-bipiperidin-1'-carboxylate (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxoquinolin-1 (2H) -yl) methyl
404 image362 1- (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2oxoquinolin-1 (2H) -yl) -2-calcium methylpropyl phosphate
405 image363 1- (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxoquinolin-1 (2H) -yl) ethyl dimethylcarbamate
Example Structural Formula image364
406 image365 1- (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxoquinolin-1 (2H) -yl) ethyl methyl (tetradecyl) carbamate
407 image366 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxoquinolin-1 (2H) -yl) methyl 4-acetamidobutanoate
408 image367 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxoquinolin-1 (2H) -yl) methyl 4-heptanamidobutanoate
409 image368 1- (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxoquinolin-1 (2H) -yl) ethyl dinonylcarbamate
410 image369 1- (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxoquinolin-1 (2H) -yl) ethyl ditetradecylcarbamate
411 image370 (7- (4- (4- (benzo [b] thiophenyl) piperazin-1-yl) butoxy) -2-oxoquinolin-1 (2H) -yl) methyl 4-heptanamidobutanoate
412 image371 henicosa-5,8,11,14,17-pentaenoate (5Z, 8Z, 11Z, 14Z, 17Z) - (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxoquinolin-1 (2H) -yl) methyl
Example Structural Formula image372
413 image373 Pentacosa-7,10,13,16,19-pentaenoate (7Z, 10Z, 13Z, 16Z, 19Z) - (7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1il) butoxy) -2-oxoquinolin-1 (2H) -yl) methyl
414 image374 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl acetate
415 image375 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl propionate
416 image376 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl butyrate
417 image377 (7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl pentanoate
418 image378 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl hexanoate
419 image379 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl heptanoate
420 image380 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl octanoate
421 image381 (7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl nonanoate
422 image382 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl decanoate
Example Structural Formula image383
423 image384 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl undecanoate
424 image385 (7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl tridecanoate
425 image386 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl tetradecanoate
426 image387 (7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl pentadecanoate
427 image388 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl palmitate
428 image389 (7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl heptadecanoate
429 image390 (7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl stearate
430 image391 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl icosanoate
431 image392 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl 2,2-dimethyltetradecanoate
432 image393 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl pivalate
433 image394 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl 2,2-dimethylbutanoate
434 image395 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl isobutyrate
Example Structural Formula image396
435 image397 2-hydroxyacetate (7- (4- (4- (benzo [b] thiophene-4, -yl) piperazin-1yl) butoxy) quinolin-2-yloxy) methyl
436 image398 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl cyclopropanecarboxylate
437 image399 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl cyclobutanecarboxylate
438 image400 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl cyclopentanecarboxylate
439 image401 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl cyclohexanecarboxylate
440 image402 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl benzoate
441 image403 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl 2-phenylacetate
442 image404 (9Z, 12Z, 15Z) octadeca-9,12,15-trienoate - (7- (4- (4 (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl
443 image405 henicosa-5,8,11,14,17-pentaenoate (5Z, 8Z, 11 Z, 14Z, 17Z) - (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1il ) butoxy) quinolin-2-yloxy) methyl
444 image406 docosa-4,7,10,13,16,19-hexaenoate (4Z, 7Z, 10Z, 13Z, 16Z, 19Z) - (7- (4- (4- (4- (benzo [b] thiophene-4-yl)) piperazin-1yl) butoxy) quinolin-2-yloxy) methyl
445 image407 octadeca-6,9,12,15-tetraenoate (6Z, 9Z, 12Z, 15Z) - (7- (4 (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin -2yloxy) methyl
Example Structural Formula image408
446 image409 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl methyl carbonate
447 image410 (7- (4- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl ethyl carbonate
448 image411 (7- (4- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl butylcarbonate
449 image412 (7- (4- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl pentylcarbonate
450 image413 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl 2-methoxycarbonate
451 image414 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) calcium methyl phosphate
452 image415 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl methylcarbamate
453 image416 (7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl ethylcarbamate
454 image417 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl propylcarbamate
455 image418 (7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl butylcarbamate
Example Structural Formula image419
456 image420 (7- (4- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl pentylcarbamate
457 image421 (7- (4- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl hexylcarbamate
458 image422 (7- (4- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl octylcarbamate
459 image423 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl dodecylcarbamate
460 image424 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl tetradecylcarbamate
461 image425 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl hexadecylcarbamate
462 image426 (7- (4- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl dimethylcarbamate
463 image427 (7- (4- (4- (4- (benzo [b] thiophene-4, -yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl diethylcarbamate
464 image428 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl dipropylcarbamate
465 image429 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl diisobutylcarbamate
466 image430 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl dibutylcarbamate
Example Structural Formula image431
467 image432 (7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl dihexylcarbamate
468 image433 (7- (4- (4- (benzo [b] thiophen-4-yl) piperazin1-yl) butoxy) quinolin-2-yloxy) methyl dioctylcarbamate
469 image434 (7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl didecylcarbamate
470 image435 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl didodecylcarbamate
471 image436 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl ditetradecylcarbamate
472 image437 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl dihexadecylcarbamate
473 image438 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl bis (2-hydroxyethyl) carbamate
474 image439 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl piperidine-1-carboxylate
475 image440 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl 4-methylpiperazin-1-carboxylate
476 image441 (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl 1,4'-bipiperidin-1'-carboxylate
Example Structural Formula image442
477 * image443 1-acetyl-7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) quinolin-2 (1H) -one
478 * image444 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1propionylquinolin-2 (1H) -one
479 * image445 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1butyrylquinolin-2 (1H) -one
480 * image446 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1pentanoylquinolin-2 (1H) -one
481 * image447 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1- (3-methylbutanoyl) quinolin-2 (1 H) -one
482 * image448 7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -1hexanoylquinolin-2 (1H) -one
483 * image449 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1hexanoyl-3,4-dihydroquinolin-2 (1 H) -one
484 * image450 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1heptanoylquinolin-2 (1H) -one
485 * image451 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1octanoylquinolin-2 (1 H) -one
486 * image452 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1-octanoyl3,4-dihydroquinolin-2 (1H) -one
487 * image453 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1nonanoylquinolin-2 (1H) -one
Example Structural Formula image454
488 * image455 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1decanoylquinolin-2 (1H) -one
489 * image456 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1undecanoylquinolin-2 (1H) -one
490 * image457 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1dodecanoylquinolin-2 (1H) -one
491 * image458 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1tridecanoylquinolin-2 (1H) -one
492 * image459 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1-tetradecanoylquinolin-2 (1H) -one
493 * image460 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1pentadecanoylquinolin-2 (1H) -one
494 * image461 7- (4- (4- (benzo [bjtiofen-4-yl) piperazin-1-yl) butoxy) -1palmitoylquinolin-2 (1H) -one
495 * image462 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1heptadecanoylquinolin-2 (1H) -one
496 * image463 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1-stearoylquinolin-2 (1H) -one
497 * image464 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1nonadecanoylquinolin-2 (1H) -one
498 * image465 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1icosanoylquinolin-2 (1H) -one
Example Structural Formula image466
499 * image467 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1henicosanoylquinolin-2 (1H) -one
500 * image468 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1docosanoylquinolin-2 (1H) -one
501 * image469 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1tricosanoylquinolin-2 (1H) -one
502 * image470 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1-tetracosanoylquinolin-2 (1H) -one
503 * image471 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1- (2-methylbutanoyl) quinolin-2 (1 H) -one
504 * image472 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1isobutyrylquinolin-2 (1H) -one
505 * image473 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1isobutyryl-3,4-dihydroquinolin-2 (1H) -one
506 * image474 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1- (2-methylpentanoyl) quinolin-2 (1H) -one
507 * image475 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1- (2-methylhexanoyl) quinolin-2 (1H) -one
508 * image476 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1- (2,2-dimethylhexanoyl) quinolin-2 (1H) -one
Example Structural Formula image477
509 * image478 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1- (2,2-dimethyloctanoyl) quinolin-2 (1 H) -one
510 * image479 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1- (2,2-dimethyloctanoyl) -3,4-dihydroquinolin-2 (1H) -one
511 * image480 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1- (2,2-dimethyldecanoyl) quinolin-2 (1 H) -one
512 image481 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1- (2-phenylacetyl) quinolin-2 (1H) -one
513 * image482 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1benzoylquinolin-2 (1H) -one
514 * image483 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1-benzoyl3,4-dihydroquinolin-2 (1H) -one
515 image484 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1 (cyclobutanecarbonyl) quinolin-2 (1H) -one
516 image485 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1 (cyclopentanecarbonyl) quinolin-2 (1H) -one
517 image486 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1 (cyclohexanecarbonyl) quinolin-2 (1H) -one
518 image487 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1 (cycloheptanecarbonyl) quinolin-2 (1H) -one
Example Structural Formula image488
519 * image489 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1-pivaloylquinolin-2 (1H) -one
520 image490 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1- (2-hydroxyacetyl) quinolin-2 (1H) -one
521 image491 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1- (2-hydroxyacetyl) -3,4-dihydroquinolin-2 (1H) -one
522 image492 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1 (4Z, 7Z, 10Z, 13Z, 16Z, 19Z) -docosa-4,7,10 , 13,16,19 hexaenoylquinolin-2 (1H) -one
523 image493 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1 (9Z, 12Z, 15Z) -octadeca-9,12,15-trienoylquinolin-2 (1H ) -one
524 image494 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1 (5Z, 8Z, 11Z, 14Z, 17Z) -henicosa-5,8,11,14 , 17pentaenoylquinolin-2 (1H) -one
525 image495 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1 (6Z, 9Z, 12Z, 15Z) -octadeca-6,9,12,15-tetraenoylquinolin2 (1H) -one
526 image496 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1 (7Z, 10Z, 13Z, 16Z, 19Z) -docosa-7,10,13,16 , 19pentaenoylquinolin-2 (1H) -one
527 image497 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1 (4Z, 7Z, 10Z, 13Z, 16Z) -docosa-4,7,10,13 , 16pentaenoylquinolin-2 (1H) -one
Example Structural Formula image498
528 image499 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1 (4Z, 7Z, 10Z, 13Z, 16Z, 19Z) -docosa-4,7,10 , 13,16,19 hexaenoylquinolin-2 (1H) -one
529 image500 2-amino-N- (2- (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxoquinolin-1 (2H) -yl) -2- oxoethyl) acetamide
530 image501 2-amino-N- (2- (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxoquinolin-1 (2H) -yl) -2- oxoethyl) propanamide
531 image502 2-amino-N- (2- (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxoquinolin-1 (2H) -yl) -2- oxoethyl) -3 methylbutanamide
532 image503 2-amino-N- (2- (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxoquinolin-1 (2H) -yl) -2- oxoethyl) -4methylpentanamide
533 image504 N- (4- (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2oxoquinolin-1 (2H) -yl) -4-oxobutyl) acetamide
534 image505 N- (4- (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2oxo-3,4-dihydroquinolin-1 (2H) -yl) - 4-oxobutyl) acetamide
535 image506 N- (4- (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2oxoquinolin-1 (2H) -yl) -4-oxobutyl) heptanamide
Example Structural Formula image507
536 image508 1- (2-aminoacetyl) -7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1yl) butoxy) quinolin-2 (1H) -one
537 image509 1- (2-aminopropanoyl) -7- (4- (4- (benzo [b] thiophen-4-yl) piperazin1-yl) butoxy) quinolin-2 (1H) -one
538 image510 1- (2-amino-4-methylpentanoyl) -7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2 (1H) -one
539 image511 2-amino-N- (2- (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxoquinolin-1 (2H) -yl) -2- oxoethyl) acetamide
540 image512 2-amino-N- (1- (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxoquinolin-1 (2H) -yl) -3- methyl-1-oxobutan-2il) acetamide
541 image513 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1 (pyrrolidin-2-carbonyl) quinolin-2 (1H) -one
542 image514 1- (1- (2-aminoacetyl) pyrrolidin-2-carbonyl) -7- (4- (4 (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2 (1H) - ona
543 image515 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1- (2- (2-methoxyethoxy) acetyl) quinoli n-2 (1H) -one
544 image516 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1- (2- (2-methoxyethoxy) acetyl) -3,4-dihydroquinolin-2 (1H) - ona
545 image517 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1- (2- (2- (2-methoxyethoxy) ethoxy) acetyl) quinolin-2 (1H) - ona
Example Structural Formula image518
546 image519 7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2oxoquinolin-1 (2H) -methyl carboxylate
547 image520 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -2-oxo-3,4-dihydroquinolin-1 (2H) -methyl carboxylate
548 image521 7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2oxoquinolin-1 (2H) -ethyl carboxylate
549 image522 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -2oxoquinolin-1 (2H) -propyl carboxylate
550 image523 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -2-oxo-3,4-dihydroquinolin-1 (2H) -propyl carboxylate
551 image524 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -2oxoquinolin-1 (2H) -isobutyl carboxylate
552 image525 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -2oxoquinolin-1 (2H) -butyl carboxylate
553 image526 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -2oxoquinolin-1 (2H) -pentyl carboxylate
554 image527 7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxo-3,4-dihydroquinolin-1 (2H) -pentyl carboxylate
555 image528 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -2oxoquinolin-1 (2H) -hexyl carboxylate
Example Structural Formula image529
556 image530 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -2oxoquinolin-1 (2H) -isopentyl carboxylate
557 image531 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -2oxoquinolin-1 (2H) -isopropyl carboxylate
558 image532 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -2-oxo-3,4-dihydroquinolin-1 (2H) -isopropyl carboxylate
559 image533 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -2oxoquinolin-1 (2H) -cyclohexylcarboxylate
560 image534 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -2-oxo-3,4-dihydroquinolin-1 (2H) -cyclohexyl carboxylate
561 image535 7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2oxoquinolin-1 (2H) -heptyl carboxylate
562 image536 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -2-oxo-3,4-dihydroquinolin-1 (2H) -heptyl carboxylate
563 image537 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -2oxoquinolin-1 (2H) -octyl carboxylate
564 image538 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -2oxoquinolin-1 (2H) -nonyl carboxylate
Example Structural Formula image539
565 image540 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -2oxoquinolin-1 (2H) -decyl carboxylate
566 image541 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -2oxoquinolin-1 (2H) -decyl carboxylate
567 image542 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -2-oxo-3,4-dihydroquinolin-1 (2H) -decyl carboxylate
568 image543 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -2oxoquinolin-1 (2H) -dodecyl carboxylate
569 image544 7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2oxoquinolin-1 (2H) -tridecyl carboxylate
570 image545 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -2oxoquinolin-1 (2H) -tetradecyl carboxylate
571 image546 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -2oxoquinolin-1 (2H) -pentadecyl carboxylate
572 image547 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -2oxoquinolin-1 (2H) -hexadecyl carboxylate
573 image548 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -2oxoquinolin-1 (2H) -heptadecyl carboxylate
574 image549 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -2oxoquinolin-1 (2H) -odedecyl carboxylate
Example Structural Formula image550
575 image551 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -2oxoquinolin-1 (2H) -naonacylcarboxylate
576 image552 7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2oxoquinolin-1 (2H) -icosycarboxylate
577 image553 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -2oxoquinolin-1 (2H) -henicosylcarboxylate
578 image554 7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2oxoquinolin-1 (2H) -docosyl carboxylate
579 image555 7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2oxoquinolin-1 (2H) -benzyl carboxylate
580 image556 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -N-benzyl2-oxoquinolin-1 (2H) -carboxamide
581 image557 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -2oxoquinolin-1 (2H) -calcium phosphate
582 image558 7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxo-3,4-dihydroquinolin-1 (2H) -calcium phosphate
583 image559 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -N-methyl-2oxoquinolin-1 (2H) -carboxamide
584 image560 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -N-methyl-2oxo-3,4-dihydroquinolin-1 (2H) -carboxamide
Example Structural Formula image561
585 image562 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -N-ethyl-2oxoquinolin-1 (2H) -carboxamide
586 image563 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -2-oxo-N-propylquinolin-1 (2H) -carboxamide
587 image564 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -N-butyl-2oxoquinolin-1 (2H) -carboxamide
588 image565 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -2-oxo-N-pentylquinolin-1 (2H) -carboxamide
589 image566 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -N-hexyl-2oxoquinolin-1 (2H) -carboxamide
590 image567 7- (4- (4- (benzo [b] hyphene-4-yl) piperazin-1-yl) butoxy) -N-heptyl-2-oxoquinolin-1 (2H) -carboxamide
591 image568 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -N-heptyl-2oxo-3,4-dihydroquinolin-1 (2H) -carboxamide
592 image569 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -N-octyl-2oxoquinolin-1 (2H) -carboxamide
593 image570 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -N-nonyl-2oxoquinolin-1 (2H) -carboxamide
594 image571 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -N-decyl-2oxoquinolin-1 (2H) -carboxamide
Example Structural Formula image572
595 image573 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -N- (2-hydroxyethyl) -2-oxoquinolin-1 (2H) -carboxamide
596 image574 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -N, Ndimethyl-2-oxoquinolin-1 (2H) -carboxamide
597 image575 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -N, Ndimethyl-2-oxo-3,4-dihydroquinolin-1 (2H) -carboxamide
598 image576 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -N, N-diethyl2-oxoquinolin-1 (2H) -carboxamide
599 image577 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -2-oxoN, N-dipropylquinolin-1 (2H) -carboxamide
600 image578 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -N, Ndibutyl-2-oxoquinolin-1 (2H) -carboxamide
601 image579 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -2-oxoN, N-dipentylquinolin-1 (2H) -carboxamide
602 image580 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -N, Ndihexyl-2-oxoquinolin-1 (2H) -carboxamide
603 image581 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -N, Ndiheptyl-2-oxoquinolin-1 (2H) -carboxamide
604 image582 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -N, Ndiheptyl-2-oxo-3,4-dihydroquinolin-1 (2H) -carboxamide
Example Structural Formula image583
605 image584 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -N, Ndinonyl-2-oxoquinolin-1 (2H) -carboxamide
606 image585 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -2-oxoN, N-ditetradecylquinolin-1 (2H) -carboxamide
607 image586 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -N-methyl-2oxo-N-tetradecylquinolin-1 (2H) -carboxamide
608 image587 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -N-methyl-Nnonyl-2-oxoquinolin-1 (2H) -carboxamide
609 image588 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1 (morpholino-4-carbonyl) quinolin-2 (1H) -one
610 image589 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1 (morpholino-4-carbonyl) -3,4-dihydroquinolin-2 (1H) -one
611 image590 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -N, N-bis (2-hydroxyethyl) -2-oxoquinolin-1 (2H) -carboxamide
612 image591 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -N, Ndibenzyl-2-oxoquinolin-1 (2H) -carboxamide
613 image592 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1- (4-methylpiperazin-1-carbonyl) quinolin-2 (1H) -one
Example Structural Formula image593
614 image594 1- (1,4'-bipiperidin-1'-carbonyl) -7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2 (1H) -one
615 image595 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) -1 (cyclopropanecarbonyl) quinolin-2 (1H) -one
616 image596 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl propionate
617 image597 7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl butyrate
618 image598 7- (4- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl pentanoate
619 image599 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) quinolin-2yl hexanoate
620 image600 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl heptanoate
621 image601 7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl octanoate
622 image602 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl nonanoate
623 image603 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl decanoate
624 image604 7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl undecanoate
625 image605 7- (4- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl tridecanoate
Example Structural Formula image606
626 image607 7- (4- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl tetradecanoate
627 image608 7- (4- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl pentadecanoate
628 image609 7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl palmitate
629 image610 7- (4- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl heptadecanoate
630 image611 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl stearate
631 image612 7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl icosanoate
632 image613 7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl 2,2-dimethyltetradecanoate
633 image614 7- (4- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl pivalate
634 image615 7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl 2,2-dimethylbutanoate
635 image616 7- (4- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl isobutyrate
636 image617 7- (4- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl 2-hydroxyacetate
Example Structural Formula image618
637 image619 7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl cyclopropanecarboxylate
638 image620 7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl cyclobutanecarboxylate
639 image621 7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl cyclopentanecarboxylate
640 image622 7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl benzoate
641 image623 7- (4- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl-2-phenylacetate
642 image624 octadeca-9,12,15-trienoate (9Z, 12Z, 15Z) -7- (4- (4 (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl
643 image625 henicosa-5,8,11,14,17-pentaenoate (5Z, 8Z, 11Z, 14Z, 17Z) -7- (4- (4- (benzo [b] thiophene-4-yl) piperazin1-yl) butoxy ) quinolin-2-yl
644 image626 docosa-4,7,10,13,16,19-hexaenoate (4Z, 7Z, 10Z, 13Z, 16Z, 19Z) -7- (4- (4- (benzo [b] thiophene-4il) piperazin-1 -yl) butoxy) quinolin-2-yl
645 image627 octadeca-6,9,12,15-tetraenoate (6Z, 9Z, 12Z, 15Z) -7- (4 (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin- 2-yl
646 image628 7- (4- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl methylcarbonate
647 image629 7- (4- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl ethyl carbonate
648 image630 7- (4- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl butyl carbonate
Example Structural Formula image631
649 image632 7- (4- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl pentylcarbonate
650 image633 7- (4- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl cyclohexylcarbonate
651 image634 7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl 2-methoxyethylcarbonate
652 image635 calcium diethyl phosphate 7- (4- (4- (benzo [b] thiophene-4-yl) piperazin1-yl) butoxy) quinolin-2-yl
653 image636 7- (4- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl methylcarbamate
654 image637 7- (4- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl ethylcarbamate
655 image638 7- (4- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl propylcarbamate
656 image639 7- (4- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl butylcarbamate
657 image640 7- (4- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl pentylcarbamate
658 image641 7- (4- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl hexylcarbamate
659 image642 7- (4- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl octylcarbamate
660 image643 7- (4- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl decylcarbamate
Example Structural Formula image644
661 image645 7- (4- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl dodecylcarbamate
662 image646 7- (4- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl tetradecylcarbamate
663 image647 7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl hexadecylcarbamate
664 image648 7- (4- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl dimethylcarbamate
665 image649 7- (4- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl dipropylcarbamate
666 image650 7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl diisobutylcarbamate
667 image651 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin1-yl) butoxy) quinolin-2-yl dibutylcarbamate
668 image652 7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl dihexylcarbamate
669 image653 7- (4- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl dioctylcarbamate
670 image654 7- (4- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl didecylcarbamate
671 image655 7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl didodecylcarbamate
Example Structural Formula image656
672 image657 7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl ditetradecylcarbamate
673 image658 7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl dihexadecylcarbamate
674 image659 7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl bis (2-hydroxyethyl) carbamate
675 image660 7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl piperidine-1-carboxylate
676 image661 7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl 4-methylpiperazin-1-carboxylate
677 image662 7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl 1,4'-bipiperidin-1'-carboxylate
678 image663 4- (benzo [b] thiophen4-yl) -1- (4- (2-oxo-1,2-dihydroquinolin-7-yloxy) butyl) -1- (propionyloxymethyl) piperazin1-io chloride
679 image664 4- (benzo [b] thiophen-4-yl) -1- (butyryloxymethyl) -1- (4- (2oxo-1,2-dihydroquinolin-7-yloxy) butyl) piperazin-1-io chloride
680 image665 4- (benzo [b] thiophen-4-yl) -1- (4- (2-oxo-1,2-dihydroquinolin-7-yloxy) butyl) -1- (pentanoyloxymethyl) piperazin-1-chloride
Example Structural Formula image666
681 image667 4- (benzo [b] thiophen-4-yl) -1- (hexanoyloxymethyl) -1- (4 (2-oxo-1,2-dihydroquinolin-7-yloxy) butyl) piperazin-1-io chloride
682 image668 4- (benzo [b] thiophen-4-yl) -1- (heptanoyloxymethyl) -1- (4 (2-oxo-1,2-dihydroquinolin-7-yloxy) butyl) piperazin-1-io chloride
683 image669 4- (benzo [b] thiophen-4-yl) -1- (octanoyloxymethyl) -1- (4 (2-oxo-1,2-dihydroquinolin-7-yloxy) butyl) piperazin-1-io chloride
684 image670 4- (benzo [b] thiophen-4-yl) -1- (nonanoyloxymethyl) -1- (4 (2-oxo-1,2-dihydroquinolin-7-yloxy) butyl) piperazin-1-io chloride
685 image671 4- (benzo [b] thiophene-4-yl) -1- (decanoyloxymethyl) -1- (4 (2-oxo-1,2-dihydroquinolin-7-yloxy) butyl) piperazin-1-io chloride
686 image672 4- (benzo [b] thiophene-4-yl) -1- (4- (2-oxo-1,2-dihydroquinolin-7-yloxy) butyl) -1 (undecanoyloxymethyl) piperazin-1-io iodide
687 image673 4- (benzo [b] thiophen-4-yl) -1- (4- (2-oxo-1,2-dihydroquinolin-7-yloxy) butyl) -1 (tetradecanoyloxymethyl) piperazin-1-io iodide
688 image674 4- (benzo [b] thiophene-4-yl) -1- (4- (2-oxo-1,2-dihydroquinolin-7-yloxy) butyl) -1- (palmitoyloxymethyl) piperazin-1io iodide
Example Structural Formula image675
689 image676 4- (benzo [b] thiophene-4-yl) -1- (4- (2-oxo-1,2-dihydroquinolin-7-yloxy) butyl) -1- (stearoyloxymethyl) piperazin1-io iodide
690 image677 4- (benzo [b] thiophene-4-yl) -1- (icosanoyloxymethyl) -1- (4 (2-oxo-1,2-dihydroquinolin-7-yloxy) butyl) piperazin-1-io iodide
691 image678 4- (benzo [b] thiophen-4-yl) -1- (docosanoyloxymethyl) -1 (4- (2-oxo-1,2-dihydroquinolin-7-yloxy) butyl) piperazin-1-io iodide
692 image679 4- (benzo [b] thiophene-4-yl) -1 (cyclopentanecarbonyloxymethyl) -1- (4- (2-oxo-1,2-dihydroquinolin-7-yloxy) butyl) piperazin-1-io iodide
693 image680 4- (benzo [b] thiophene-4-yl) -1 (cyclohexanecarbonyloxymethyl) iodide -1- (4- (2-oxo-1,2-dihydroquinolin-7-yloxy) butyl) piperazin-1-io iodide
694 image681 4- (benzo [b] thiophen-4-yl) -1- (isobutyryloxymethyl) -1- (4 (2-oxo-1,2-dihydroquinolin-7-yloxy) butyl) piperazin-1-io chloride
695 image682 4- (benzo [b] thiophen-4-yl) -1- (4- (2-oxo-1,2-dihydroquinolin-7-yloxy) butyl) -1 - ((2-propylpentanoyloxy) methyl) piperazin-1-io iodide
Example Structural Formula image683
696 image684 4- (benzo [b] thiophene-4-yl) -1- (4- (2-oxo-1,2-dihydroquinolin-7-yloxy) butyl) -1 - ((2-pentheptanoyloxy) methyl) piperazin-1-io iodide
697 image685 4- (benzo [b] thiophen-4-yl) -1- (4- (2-oxo-1,2-dihydroquinolin-7-yloxy) butyl) -1- (pivaloyloxymethyl) piperazin-1io chloride
698 image686 4- (benzo [b] thiophen-4-yl) -1 - ((2,2-dimethylbutanoyloxy) methyl) -1- (4- (2-oxo-1,2-dihydroquinolin-7-yloxy) butyl) piperazin-1 iodide -io
699 image687 4- (benzo [b] thiophene-4-yl) -1 - ((2,2-dimethylpentanoyloxy) methyl) -1- (4- (2-oxo-1,2-dihydroquinolin7-yloxy) butyl) piperazin-1 iodide -io
700 image688 4- (benzo (b) thiophene-4-yl) -1 - ((2,2-dimethylhexanoyloxy) methyl) -1- (4- (2-oxo-1,2-dihydroquinolin-7-yloxy) butyl) piperazin-1 iodide -io
701 image689 4- (benzo [b] thiophen-4-yl) -1 - ((2,2-dimethyltetradecanoyloxy) methyl) -1- (4- (2-oxo-1,2-dihydroquinolin-7-yloxy) butyl) piperazin-1 iodide -io
702 image690 4- (benzo [b] thiophene-4-yl) -1 - ((1-methylcyclohexanecarbonyloxy) methyl) -1- (4- (2-oxo-1,2-dihydroquinolin-7-yloxy) butyl) piperazin-1-io iodide
Example Structural Formula image691
703 image692 4- (benzo [b] thiophene-4-yl) -1 ((hexylcarbamoyloxy) methyl) -1- (4- (2-oxo-1,2-dihydroquinolin-7-yloxy) butyl) piperazin-1-io iodide
704 image693 4- (benzo [b] thiophen-4-yl) -1 ((diethylcarbamoyloxy) methyl) -1- (4- (2-oxo-1,2-dihydroquinolin7-yloxy) butyl) piperazin-1-io iodide
705 image694 4- (benzo [b] thiophene-4-yl) -1 ((dibenzylcarbamoyloxy) methyl) -1- (4- (2-oxo-1,2-dihydroquinolin-7-yloxy) butyl) piperazin-1-io iodide
706 image695 4- (benzo [b] thiophen-4-yl) -1- (4- (2-oxo-1,2-dihydroquinolin-7-yloxy) butyl) -1 - ((piperidin-1-carbonyloxy) methyl) piperazin -1 iodide -io
707 image696 4- (benzo [b] thiophen-4-yl) -1 - ((ethoxycarbonyloxy) methyl) 1- (4- (2-oxo-1,2-dihydroquinolin-7-yloxy) butyl) piperazin-1- chloride io
708 image697 4- (benzo [b] thiophen-4-yl) -1 (((cyclohexyloxycarbonyloxy) methyl) -1- (4- (2-oxo-1,2-dihydroquinolin-7-yloxy) butyl) piperazin-1-io chloride
709 image698 4- (benzo [b] thiophene-4-yl) -1 ((hexyloxycarbonyloxy) methyl) -1- (4- (2-oxo-1,2-dihydroquinolin-7-yloxy) butyl) piperazin-1-io iodide
Example Structural Formula image699
710 image700 4- (benzo [b] thiophene-4-yl) -1- (4- (2-oxo-1,2-dihydroquinolin-7-yloxy) butyl) -1 - ((((pentan-3-yloxy) carbonyloxy) methyl) iodide) piperazin-1-io
711 image701 4- (benzo [b] thiophen-4-yl) -1- (benzoyloxymethyl) -1- (4 (2-oxo-1,2-dihydroquinolin-7-yloxy) butyl) piperazin-1-io chloride
712 image702 4- (benzo [b] thiophen-4-yl) -1- (4- (2-oxo-1,2-dihydroquinolin-7-yloxy) butyl) -1 - (((2-phenylacetoxy) methyl) piperazin-1-io chloride
713 image703 bis ((7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxoquinolin-1 (2H) -yl) methyl) succinate)
714 image704 bis ((7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxo-3,4-dihydroquinolin-1 (2H) -yl) methyl) succinate)
715 image705 bis ((7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxoquinolin-1 (2H) -yl) methyl) glutarate)
716 image706 bis ((7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxo-3,4-dihydroquinolin-1 (2H) -yl) methyl) glutarate)
Example Structural Formula image707
717 image708 bis ((7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxoquinolin-1 (2H) -yl) methyl) adipate
718 image709 bis ((7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxo-3,4-dihydroquinolin-1 (2H) -yl) methyl) adipate
719 image710 bis ((7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxoquinolin-1 (2H) -yl) methyl) heptanedioate
720 image711 bis ((7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxo-3,4-dihydroquinolin-1 (2H) yl) methyl heptanedioate
721 image712 bis ((7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxoquinolin-1 (2H) -yl) methyl octanedioate)
722 image713 bis ((7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxo-3,4-dihydroquinolin-1 (2H) -yl) methyl octanedioate)
723 image714 bis ((7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxoquinolin-1 (2H) -yl) methyl) decanedioate
724 image715 bis ((7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxo-3,4-dihydroquinolin-1 (2H) -yl) methyl) decanedioate
Example Structural Formula image716
725 image717 bis ((7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxoquinolin-1 (2H) -yl) methyl) dodecanedioate
726 image718 bis ((7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxo-3,4-dihydroquinolin-1 (2H) yl) methyl dodecanedioate dodecanedioate
727 image719 bis ((7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxoquinolin-1 (2H) -yl) methyl tetradecanedioate
728 image720 bis ((7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxo-3,4-dihydroquinolin-1 (2H) yl) methyl tetradecanedioate
729 image721 bis ((7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxoquinolin-1 (2H) -yl) methyl) hexadecanedioate
730 image722 bis ((7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxo-3,4-dihydroquinolin-1 (2H) yl) methyl hexadecanedioate
731 image723 bis ((7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxoquinolin-1 (2H) -yl) methyl octadecanedioate)
Example Structural Formula image724
732 image725 bis ((7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxo-3,4-dihydroquinolin-1 (2H) yl) methyl octadecanedioate
733 image726 bis ((7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxoquinolin-1 (2H) -yl) methyl) icosanodioate
734 image727 bis ((7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxo-3,4-dihydroquinolin-1 (2H) -yl) methyl) icosanodioate
735 image728 bis ((7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxoquinolin-1 (2H) -yl) methyl) docosanodioate
736 image729 bis ((7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) -2-oxo-3,4-dihydroquinolin-1 (2H) yl) methyl docosanodioate
737 image730 bis ((7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl succinate)
738 image731 bis ((7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl) glutarate)
739 image732 bis ((7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl) adipate)
Example Structural Formula image733
740 image734 bis ((7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl heptanedioate)
741 image735 bis ((7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl octanedioate)
742 image736 bis ((7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl decanedioate)
743 image737 bis ((7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl dodecanedioate)
744 image738 bis ((7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl tetradecanedioate)
745 image739 bis ((7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl) hexadecanedioate)
746 image740 bis ((7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl octadecanedioate)
747 image741 bis ((7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl icosanodioate)
Example Structural Formula image742
748 image743 bis ((7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yloxy) methyl docosanodioate)
749 image744 bis (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl) succinate)
750 image745 bis (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl) glutarate
751 image746 bis (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl) adipate
752 image747 bis (7- (4- (4- (benzo [b] thiophen-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl) heptanedioate
753 image748 bis (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl) octanedioate
754 image749 bis (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl) decanedioate
755 image750 bis (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl) dodecanedioate
Example Structural Formula image751
756 image752 bis (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl) tetradecanedioate
757 image753 bis (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl) hexadecanedioate
758 image754 bis (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl) octadecanedioate
759 image755 bis (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl) icosanodioate
760 image756 bis (7- (4- (4- (benzo [b] thiophene-4-yl) piperazin-1-yl) butoxy) quinolin-2-yl) docosanodioate
* example that is not within the scope of the claimed invention
Example A: Synthesis of 7- [4- (4-benzo [b] thiophen-4-yl-piperazin-1-yl) -butoxy] -1H-quinolin-2-one A-1: Synthesis of 7- [4- (4-benzo [b] thiophen-4-yl-piperazin-1-yl) -butoxy-1,1,2,2,3,3,4,4-d8] -1H-quinolin-2- one (synthesis method 1)
step 1: Synthesis of 2-benzyloxy-7- (4-bromobutoxy-1,1,2,2,3,3,4,4-d8) quinoline
image757
To a mixture of 2-benzyloxy-7-hydroxyquinoline (2.52 g) and potassium carbonate (1.67 g) in dimethylformamide (25 ml) was added 1,4-dibromobutane-d8 (99.6% of D atom: 2.4 ml), and the mixture was stirred at room temperature overnight. To the reaction mixture was added water, ethyl acetate, insoluble matter was filtered off, and the filtrate was partitioned, washed with water, and dried over sodium sulfate. The solvent was evaporated under reduced pressure. The residue was purified by silica gel column chromatography (n
15 hexane: ethyl acetate = 10: 0 → 9: 1) to provide 2-benzyloxy-7- (4-bromobutoxy-1,1,2,2,3,3,4,4-d8) quinoline (3, 14 g) 2-benzyloxy-7- (4-bromobutoxy-1,1,2,2,3,3,4,4-d8) quinoline: white powder, H1 NMR (CDCl3) δ: 5.52 (2H, s ), 6.81 (1H, d, J = 8.7Hz), 7.02 (1H, dd, J = 8.8, 2.5Hz), 7.21 (1H, d, J = 2.5Hz) , 7.29-7.47 (3H, m), 7.49-7.56 (2H, m), 7.60
image758
image759
image760
image761
image762
image763
image764
image765
image766
image767
image768
image769
image770
image771
image772
image773
image774

权利要求:
Claims (7)
[1]
image 1
image2
image3
image4
image5
image6
(4)  a tetrahydropyranyl group,
(5)  a C1-C6 alkoxycarbonyl C1-C6 alkyl group,
(6)  a (C1-C6) alkoxy (C1-C6) alkoxy C1-C6 alkyl group
(7)  a C1-C6 aminoalkyl group optionally having an alkyl (1-C6) carbonyl group, or
(8)  the next group
image7
wherein Ac 'is a C1-C30 alkyl group, Y1a is a C1-C6 alkylene group and the other symbols are defined as in claim 1,
R4a
is
(one)  a C1-C30 alkyl group, or 15 (2) a C3-C20 cycloalkyl group; Y
A is a C1-C6 alkylene group,
or a salt thereof. twenty
[4]
4. The heterocyclic compound according to claim 2, wherein R1 is the next group
image8
where 25
R8a '
is
(1) a C1-C30 alkyl group,
(2) a C3-C20 cycloalkyl group, 30 (3) a C1-C6 alkoxy group,
(4)  a cycloalkyl (C3-C20) oxy group,
(5)  a (C1-C6) alkoxy C1-C6 alkoxy group, or
(6)  an amino group optionally having 1 or 2 substituents selected from the group consisting of a C1-C30 alkyl group and a C1-C6 alkyl group substituted with hydroxy, or
35 the next group
image9
where
R9a '
it's 40
(one)  a C1-C30 alkyl group,
(2)  a C1-C6 alkyl group substituted with hydroxy,
(3)  a C3-C20 cycloalkyl group,
(4) a C1-C6 alkoxy group, 45 (5) a cycloalkyl (C3-C20) oxy group,
(6)  a C1-C6 alkoxy group C1-C6 alkoxy,
(7)  a phenyloxy group,
(8)  an amino group optionally having 1 or 2 substituents selected from the group consisting
in a C1-C30 alkyl group, 190
(9)  a piperidyl group optionally having a piperidyl group, or
(10) a piperazinyl group optionally having a C1-C6 alkyl group; R2 is the next group
image10
or
where
Y1a is a C1-C6 alkylene group, Y2a is a C1-C6 alkylene group,
R3a '
is
(one)  a C1-C30 alkyl group,
(2)  a C3-C20 cycloalkyl group
(3) a piperidyl group optionally having 1 or 2 substituents selected from the group consisting of a C1-C6 alkyl group,
(4)  a tetrahydropyranyl group,
(5)  a C1-C6 alkoxycarbonyl C1-C6 alkyl group,
(6)  a (C1-C6) alkoxy (C1-C6) alkoxy C1-C6 alkyl group
(7)  a C1-C6 aminoalkyl group optionally having an alkyl (1-C6) carbonyl group,
R4a
is
(one)  a C1-C30 alkyl group, or
(2)  a C3-C20 cycloalkyl group;
or a salt thereof.
[5]
5. A pharmaceutical composition comprising the heterocyclic compound according to claim 1
or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable diluent and / or carrier.
[6]
6. A prophylactic and / or therapeutic agent for a neurological disease of the central nervous system, comprising the heterocyclic compound according to claim 1 or a pharmaceutically acceptable salt thereof as an active ingredient.
[7]
7. The agent according to claim 6, wherein the neurological disease of the central nervous system is selected from the group consisting of schizophrenia, treatment resistant schizophrenia, refractory
or chronic, emotional disturbances, psychotic disorders, mood disorders, bipolar disorder, mania, depression, endogenous depression, major depression, melancholic and treatment-resistant depression, dysthymic disorder, cyclothymic disorder, anxiety disorder, somatomorphic disorder, factitious disorder , dissociative disorder, sexual disorder, eating disorder, sleep disorder, adaptation disorder, substance use disorder, anhedonia, delirium, Alzheimer's disease, Parkinson's disease, cognitive impairment, cognitive impairment associated with neurodegenerative diseases, cognitive impairment caused by neurodegenerative diseases, cognitive impairment in schizophrenia, cognitive impairment caused by treatment-resistant, refractory or chronic schizophrenia, vomiting, motion sickness, obesity, migraine, pain, mental retardation, autistic disorder, Tourette syndrome, tic disorder, depression disorder attention ficit with hyperactivity, behavior disorder and Down syndrome.
[8]
8. The heterocyclic compound according to claim 1 or a pharmaceutically acceptable salt thereof for use as a medicament.
[9]
9. The heterocyclic compound according to claim 1 for use in a method of prevention and / or treatment of a neurological disease of the central nervous system.
191
image11

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法律状态:

优先权:

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申请号 | 申请日 | 专利标题

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US201161532393P| true| 2011-09-08|2011-09-08|

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US201161532393P|2011-09-08|

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PCT/JP2012/073556|WO2013035892A1|2011-09-08|2012-09-07|Piperazine- substituted benzothiophene derivatives as antipsychotic agents|

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