Benzimidazole derivatives useful TRPM8 channel modulators

Patent metadata

Field	Value
Publication number	US-9636345-B2
Application number	US-201514618462-A
Country	US
Kind code	B2
Filing date	Feb 10, 2015
Priority date	Jun 10, 2009
Publication date	May 2, 2017
Grant date	May 2, 2017

Abstract

Disclosed are compounds, compositions and methods for treating various diseases, syndromes, conditions and disorders, including pain. Such compounds are represented by Formula I as follows:

wherein R 0 , R 1 , R 2 , R 3 , R 4 and a are defined herein.

First claim

We claim:

1. A method for treating cardiovascular disease aggravated by cold, including peripheral vascular disease, vascular hypertension, pulmonary hypertension, Raynaud's disease, and coronary artery disease, comprising administering to a mammal in need of such treatment a therapeutically effective amount of a compound of formula (I):

wherein:
a is an integer from 0 to 2;
each R 0 is independently selected from the group consisting of halogen, C 1-2 alkyl and fluorinated C 1-2 alkyl;
R 2 is hydrogen;
R 1 is selected from the group consisting of lower alkyl, fluorinated lower alkyl and monocyclic cycloalkyl-(lower alkyl)-;
alternatively R 2 and R 1 are taken together as

R 3 is phenyl; wherein the phenyl is optionally substituted with a substituent selected from the group consisting of halogen and fluorinated lower alkyl;
R 4 is selected from the group consisting of benzyl, 4-fluoro-benzyl, 3,4-difluoro-benzyl, 3-chloro-4-fluoro-benzyl, 4-difluoromethyl-benzyl, 3-trifluoromethyl-benzyl, 4-trifluoromethyl-benzyl, 3-trifluoromethoxy-benzyl, 4-trifluoromethoxy-benzyl, 3-fluoro-4-trifluoromethyl-benzyl, 3-trifluoromethyl-4-fluoro-benzyl, 2-fluoro-5-trifluoromethyl-benzyl and 4-trifluoromethyl-thio-benzyl;
provided that when a is 0, R 1 is methyl, R 2 is hydrogen and R 4 is methyl; then R 3 is other than methyl, phenyl or 4-methylphenyl;
or pharmaceutically acceptable salt thereof.

Assignees

• Janssen Pharmaceutica Nv

Inventors

• Macielag Mark J
• Xia Mingde
• Xu Xiaoqing

Classifications

• A61P43/00

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

• A61P9/10

  for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• A61P9/12

  Antihypertensives · CPC title

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title