Pyrazole compound

Patent metadata

Field	Value
Publication number	US-2018273489-A1
Application number	US-201815990026-A
Country	US
Kind code	A1
Filing date	May 25, 2018
Priority date	Jul 15, 2010
Publication date	Sep 27, 2018
Grant date	—

Abstract

The present invention relates to a novel serotonin reuptake inhibitor which also exhibits 5-HT 2C antagonistic action (antidepressive and anxiolytic effects), in particular, 5-HT 2C inverse agonistic action comprising Compound (1):

or a pharmaceutically acceptable salt thereof
wherein R 1 , R 2 , R 3 and R 4 are independently hydrogen or C 1-6 alkyl etc.; R 5 is C 4-7 alkyl or —(CR 8 R 9 ) r -E; R 6 , R 7 , R 8 and R 9 are independently hydrogen, fluorine or C 1-6 alkyl; A is C 6-10 aryl or heteroaryl etc.; r is 1, 2, 3 or 4; E is C 3-8 cycloalkyl or C 6-10 aryl etc.; L is oxygen, sulfur or —NR 10 —; n is 1, 2 or 3; R 10 is hydrogen or C 1-6 alkyl etc.; and X is hydrogen or halogen etc.

First claim

1 - 17 . (canceled)

18 . A compound selected from the group consisting of:
a) 1-{1-(cyclopentylmethyl)-5-[(2,5-difluorobenzyl)oxy]-1H-pyrazol-3-yl}-N-methylmethanamine; b) 1-{5-[(2,5-difluorobenzyl)oxy]-1-(3,3-dimethylbutyl)-1H-pyrazol-3-yl}-N-methylmethanamine; and c) N-methyl-1-{1-(3-methylbutyl)-5-[(2,4,5-trifluorobenzyl)oxy]-1H-pyrazol-3-yl}methanamine, or a pharmaceutically acceptable salt thereof.

19 . The compound of claim 18 , wherein the compound is 1-{1-(cyclopentylmethyl)-5-[(2,5-difluorobenzyl)oxy]-1H-pyrazol-3-yl}-N-methylmethanamine, or a pharmaceutically acceptable salt thereof.

20 . The compound of claim 18 , wherein the compound is 1-{5-[(2,5-difluorobenzyl)oxy]-1-(3,3-dimethylbutyl)-1H-pyrazol-3-yl}-N-methylmethanamine, or a pharmaceutically acceptable salt thereof.

21 . The compound of claim 18 , wherein the compound is N-methyl-1-{1-(3-methylbutyl)-5-[(2,4,5-trifluorobenzyl)oxy]-1H-pyrazol-3-yl}methanamine, or a pharmaceutically acceptable salt thereof.

22 . A citrate of a compound selected from the group consisting of:
a) 1-{1-(cyclopentylmethyl)-5-[(2,5-difluorobenzyl)oxy]-1H-pyrazol-3-yl}-N-methylmethanamine; b) 1-{5-[(2,5-difluorobenzyl)oxy]-1-(3,3-dimethylbutyl)-1H-pyrazol-3-yl}-N-methylmethanamine; c) N-methyl-1-{1-(3-methylbutyl)-5-[(2,4,5-trifluorobenzyl)oxy]-1H-pyrazol-3-yl}methanamine.

23 . The citrate of claim 22 , wherein the compound is 1-{1-(cyclopentylmethyl)-5-[(2,5-difluorobenzyl)oxy]-1H-pyrazol-3-yl}-N-methylmethanamine.

24 . The citrate of claim 22 , wherein the compound is 1-{5-[(2,5-difluorobenzyl)oxy]-1-(3,3-dimethylbutyl)-1H-pyrazol-3-yl}-N-methylmethanamine.

25 . The citrate of claim 22 , wherein the compound is N-methyl-1-{1-(3-methylbutyl)-5-[(2,4,5-trifluorobenzyl)oxy]-1H-pyrazol-3-yl}methanamine.

26 . A pharmaceutical composition comprising as an active ingredient a compound selected from the group consisting of:
a) 1-{1-(cyclopentylmethyl)-5-[(2,5-difluorobenzyl)oxy]-1H-pyrazol-3-yl}-N-methylmethanamine; b) 1-{5-[(2,5-difluorobenzyl)oxy]-1-(3,3-dimethylbutyl)-1H-pyrazol-3-yl}-N-methylmethanamine; and c) N-methyl-1-{1-(3-methylbutyl)-5-[(2,4,5-trifluorobenzyl)oxy]-1H-pyrazol-3-yl}methanamine, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

27 . The pharmaceutical composition of claim 26 , wherein the compound is 1-{1-(cyclopentylmethyl)-5-[(2,5-difluorobenzyl)oxy]-1H-pyrazol-3-yl}-N-methylmethanamine or a pharmaceutically acceptable salt thereof.

28 . The pharmaceutical composition of claim 26 , wherein the compound is 1-{5-[(2,5-difluorobenzyl)oxy]-1-(3,3-dimethylbutyl)-1H-pyrazol-3-yl}-N-methylmethanamine or a pharmaceutically acceptable salt thereof.

29 . The pharmaceutical composition of claim 26 , wherein the compound is N-methyl-1-{1-(3-methylbutyl)-5-[(2,4,5-trifluorobenzyl)oxy]-1H-pyrazol-3-yl}methanamine or a pharmaceutically acceptable salt thereof.

30 . A method for treating a disease selected from depression, anxiety, Alzheimer's disease, or Parkinson's disease, which comprises administering a therapeutically effective amount of a compound selected from the group consisting of:
a) 1-{1-(cyclopentylmethyl)-5-[(2,5-difluorobenzyl)oxy]-1H-pyrazol-3-yl}-N-methylmethanamine; b) 1-{5-[(2,5-difluorobenzyl)oxy]-1-(3,3-dimethylbutyl)-1H-pyrazol-3-yl}-N-methylmethanamine; and c) N-methyl-1-{1-(3-methylbutyl)-5-[(2,4,5-trifluorobenzyl)oxy]-1H-pyrazol-3-yl}methanamine, or a pharmaceutically acceptable salt thereof, to a mammal in need thereof.

31 . The method of claim 30 , wherein the compound is 1-{1-(cyclopentylmethyl)-5-[(2,5-difluorobenzyl)oxy]-1H-pyrazol-3-yl}-N-methylmethanamine or a pharmaceutically acceptable salt thereof.

32 . The method of claim 30 , wherein the compound is 1-{5-[(2,5-difluorobenzyl)oxy]-1-(3,3-dimethylbutyl)-1H-pyrazol-3-yl}-N-methylmethanamine or a pharmaceutically acceptable salt thereof.

33 . The method of claim 30 , wherein the compound is N-methyl-1-{1-(3-methylbutyl)-5-[(2,4,5-trifluorobenzyl)oxy]-1H-pyrazol-3-yl}methanamine or a pharmaceutically acceptable salt thereof.

34 . The method of claim 30 , wherein the disease is depression and the compound is 1-{1-(cyclopentylmethyl)-5-[(2,5-difluorobenzyl)oxy]-1H-pyrazol-3-yl}-N-methylmethanamine or a pharmaceutically acceptable salt thereof.

35 . The method of claim 30 , wherein the disease is depression and the compound is 1-{5-[(2,5-difluorobenzyl)oxy]-1-(3,3-dimethylbutyl)-1H-pyrazol-3-yl}-N-methylmethanamine or a pharmaceutically acceptable salt thereof.

36 . The method of claim 30 , wherein the disease is depression and the compound is N-methyl-1-{1-(3-methylbutyl)-5-[(2,4,5-trifluorobenzyl)oxy]-1H-pyrazol-3-yl}methanamine or a pharmaceutically acceptable salt thereof.

37 . The method of claim 30 , wherein the disease is anxiety and the compound is 1-{1-(cyclopentylmethyl)-5-[(2,5-difluorobenzyl)oxy]-1H-pyrazol-3-yl}-N-methylmethanamine or a pharmaceutically acceptable salt thereof.

38 . The method of claim 30 , wherein the disease is anxiety and the compound is 1-{5-[(2,5-difluorobenzyl)oxy]-1-(3,3-dimethylbutyl)-1H-pyrazol-3-yl}-N-methylmethanamine or a pharmaceutically acceptable salt thereof.

39 . The method of claim 30 , wherein the disease is anxiety and the compound is N-methyl-1-{1-(3-methylbutyl)-5-[(2,4,5-trifluorobenzyl)oxy]-1H-pyrazol-3-yl}methanamine or a pharmaceutically acceptable salt thereof.

40 . The method of claim 30 , wherein the disease is Alzheimer's disease and the compound is 1-{1-(cyclopentylmethyl)-5-[(2,5-difluorobenzyl)oxy]-1H-pyrazol-3-yl}-N-methylmethanamine or a pharmaceutically acceptable salt thereof.

41 . The method of claim 30 , wherein the disease is Alzheimer's disease and the compound is 1-{5-[(2,5-difluorobenzyl)oxy]-1-(3,3-dimethylbutyl)-1H-pyrazol-3-yl}-N-methylmethanamine or a pharmaceutically acceptable salt thereof.

42 . The method of claim 30 , wherein the disease is Alzheimer's disease and the compound is N-methyl-1-{1-(3-methylbutyl)-5-[(2,4,5-trifluorobenzyl)oxy]-1H-pyrazol-3-yl}methanamine or a pharmaceutically acceptable salt thereof.

43 . The method of claim 30 , wherein the disease is Parkinson's disease and the compound is 1-{1-(cyclopentylmethyl)-5-[(2,5-difluorobenzyl)oxy]-1H-pyrazol-3-yl}-N-methylmethanamine or a pharmaceutically acceptable salt thereof.

44 . The method of claim 30 , wherein the disease is Parkinson's disease and the compound is 1-{5-[(2,5-difluorobenzyl)oxy]-1-(3,3-dimethylbutyl)-1H-pyrazol-3-yl}-N-methylmethanamine or a pharmaceutically acceptable salt thereof.

45 . The method of claim 30 , wherein the disease is Parkinson's disease and the compound is N-methyl-1-{1-(3-methylbutyl)-5-[(2,4,5-trifluorobenzyl)oxy]-1H-pyrazol-3-yl}methanamine or a pharmaceutically acceptable salt thereof.

Assignees

• Sumitomo Dainippon Pharma Co Ltd

Inventors

• Sasaki Izumi
• Toyoda Tomohiro
• Yoshinaga Hidefumi
• Natsutani Itaru
• Takahashi Yoko

Classifications

• A61P9/12

  Antihypertensives · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61P5/00

  Drugs for disorders of the endocrine system · CPC title

• A61P25/18

  Antipsychotics, i.e. neuroleptics; Drugs for mania or schizophrenia · CPC title

• A61P25/04

  Centrally acting analgesics, e.g. opioids · CPC title