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N-acyl cyclic amine derivative or pharmaceutically acceptable salt thereof

A technology of medicinal salts and alkyl groups, applied in the field of N-acyl cyclic amine derivatives or their pharmaceutically acceptable salts, which can solve the problems of weight gain and schizophrenia that have not yet been described to have sufficient therapeutic effects

Inactive Publication Date: 2013-01-16
SUMITOMO PHARMA CO LTD
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, second-generation therapeutic agents for schizophrenia have not yet been described to have an adequate therapeutic effect on negative symptoms and cognitive impairment
In addition, new side effects including weight gain, abnormal glucose metabolism have become problems in second-generation therapeutic agents for schizophrenia [Non-Patent Documents 1 to 2]

Method used

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  • N-acyl cyclic amine derivative or pharmaceutically acceptable salt thereof
  • N-acyl cyclic amine derivative or pharmaceutically acceptable salt thereof
  • N-acyl cyclic amine derivative or pharmaceutically acceptable salt thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0555] (S)-(2-(2-(4-(4-fluorobenzoyl)piperidin-1-yl)ethyl)pyrrolidin-1-yl)(6-methyl-1H-indole-2 -yl)methanone

[0556] [chemical formula 24]

[0557]

[0558] To a solution of intermediate 1 (0.45 g, 1.20 mmol) and 6-methylindole-2-carboxylic acid (0.21 g, 1.20 mmol) in dimethylformamide (4.00 mL) was added triethylamine (0.85ml, 1.32mmol) and HBTU (0.50g, 1.32mmol). After stirring at room temperature for 15 hours, water and ethyl acetate were added to the mixture, and the aqueous layer was extracted with ethyl acetate. The organic layer was washed with water and brine, then dried over sodium sulfate and concentrated under reduced pressure. The resulting residue was purified with a silica gel column (chloroform / methanol = 98 / 2 to 85 / 15) to provide the title compound (0.37 g, 0.80 mmol, 67%).

[0559] MS (ESI+) 462 (M + +1, 100%).

[0560] 1 H-NMR (300 MHz, CDCl 3 ) δ 9.18 (brs, 1H), 7.99-7.94 (m, 2H), 7.54 (d, 1H, J = 7.8Hz), 7.21 (brs, 1H), 7.21 (t, 2H, J = 6.7Hz),...

Embodiment 2

[0562] (S)-(2-(2-(4-(1H-indazol-3-yl)piperazin-1-yl)ethyl)pyrrolidin-1-yl)(6-methyl-1H-indole -2-yl)methanone

[0563] [chemical formula 25]

[0564]

[0565] The title compound was obtained by a procedure similar to Example 1 using Intermediate 8.

[0566] MS (ESI+) 457 (M + +1, 100%).

[0567] 1 H-NMR (300 MHz, CDCl 3 ) δ 9.29 (brs, 1H), 7.61-7.84 (m, 2H), 7.22 (brs, 1H), 7.04 (m, 3H), 6.84 (brs, 1H), 4.53-4.39 (m, 1H), 3.99- 3.70 (m, 2H), 3.25-3.05 (m, 1H), 3.08-2.96 (m, 2H), 2.52 (s, 3H), 2.65-2.40 (m, 2H), 2.36-1.62 (m, 12H).

Embodiment 3

[0569] (S)-(2-(2-(4-(5-fluoroindolin-1-yl)ethyl)pyrrolidin-1-yl)(6-methyl-1H-indol-2-yl ) Methanone

[0570] [chemical formula 26]

[0571]

[0572] The title compound was obtained by the same procedure as in Example 1 using Intermediate 9.

[0573] MS (ESI+) 475 (M + +1, 100%).

[0574] 1 H-NMR (300 MHz, CDCl 3 ) δ 9.29 (brs, 1H), 7.84-7.61 (m, 2H), 7.22 (brs, 1H), 7.04 (m, 3H), 6.95-6.88 (t, 1H, J = 6.0Hz), 6.23 (ddd, 1H, J = 12.0, 9.0, 3.0Hz), 3.78-3.68 (brs, 1H), 3.43 (d, 2H, J = 9.0Hz), 3.20-3.17 (m, 3H), 3.05-2.97 (m, 2H) , 2.89 (t, 2H, J = 9.0Hz), 2.80 (s, 3H), 2.37 (brs, 2H), 2.04-1.82 (m, 12H).

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PUM

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Abstract

The present invention provides compounds which show high effectiveness against positive symptoms, negative symptoms and cognitive dysfunction in schizophrenia and reduce conventional side-effect risks as well as have remarkable effects for central neurological diseases associated with cognitive dysfunction other than schizophrenia. N-Acyl cyclic amine derivatives of formula (1): wherein Ar1 and Ar2 are aryl or heteroaryl; V is nitrogen, or CR3; W<1> is a single bond, -C(O)-, etc.; W<2> is C1- alkylene; W3 is a single bond, methylene, -NH-, -CR<4>=CR<5>-, etc.; Ring Q is a group of formula (a) in which n is 0 or 1; m is 0 to 2; k is 1 to 3; Z is a single bond, methylene, oxygen, etc.; R<1a>, R<1b> and R<1c> are each, same or different, hydrogen, hydroxyl, halogen, cyano, C1-6 alkyl, etc.

Description

technical field [0001] The present invention relates to N-acyl cyclic amine derivatives or pharmaceutically acceptable salts thereof. The compounds are particularly useful as therapeutic agents for psychiatric disorders, including schizophrenia, bipolar disorder, mania, major depression, affective disorders, anxiety disorders, eating disorders, attention deficit hyperactivity disorder. In addition, the present compound can also be used as a therapeutic agent for Alzheimer's disease, Parkinson's disease, Huntington's disease, epilepsy, drug dependence, drug abuse, type 2 diabetes, and obesity. Background technique [0002] The compounds disclosed in Patent Document 1, Patent Document 2, Patent Document 3 and Patent Document 4 are known as psychoactive N-acyl cyclic amine derivatives. However, these compounds have different chemical structures from the derivatives of the present invention. [0003] Schizophrenia is a disorder characterized by positive symptoms (eg, hallucina...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C07D401/14A61K31/454A61K31/4545A61K31/496A61K31/5377A61K31/55A61K31/553A61P25/18C07D403/14C07D405/06C07D405/14C07D417/12C07D417/14C07D471/04C07D471/06
CPCC07D401/14C07D413/14C07D417/14C07D405/14C07D409/14A61P25/18A61K31/437A61K31/4439C07D403/14C07D473/16C07D473/18C07D473/32
Inventor 丸山润美木之村尚也野岛俊高村昌弘柿口庆介畳谷嘉人
Owner SUMITOMO PHARMA CO LTD
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