Urea derivatives and their use as fatty-acid binding protein (FABP) inhibitors

Patent metadata

Field	Value
Publication number	US-9708340-B2
Application number	US-201514856325-A
Country	US
Kind code	B2
Filing date	Sep 16, 2015
Priority date	Mar 20, 2013
Publication date	Jul 18, 2017
Grant date	Jul 18, 2017

Abstract

The invention provides novel compounds having the general formula (I)

wherein R 1 , R 2 , R 3 , R 4 , W, A and B are as described herein, compositions including the compounds and methods of using the compounds.

First claim

The invention claimed is:

1. The compound selected from the group consisting of:
1-(Biphenyl-2-ylcarbamoyl)-piperidine-2-carboxylic acid;
(R)-1-(5-chlorobiphenyl-2-ylcarbamoyl)pyrrolidine-2-carboxylic acid;
(R)-1-(2-phenoxyphenylcarbamoyl)pyrrolidine-2-carboxylic acid;
(R)-1-(2-benzylphenylcarbamoyl)pyrrolidine-2-carboxylic acid;
(R)-1-(5-chloro-2-phenoxyphenylcarbamoyl)pyrrolidine-2-carboxylic acid;
1-(Biphenyl-2-ylcarbamoyl)-2-phenyl-pyrrolidine-2-carboxylic acid;
3-(Biphenyl-2-ylcarbamoyl)-thiazolidine-2-carboxylic acid;
(S)-3-(Biphenyl-2-ylcarbamoyl)-thiazolidine-4-carboxylic acid;
(1SR,2SR,5RS)-3-(Biphenyl-2-ylcarbamoyl)-3-aza-bicyclo[3.1.0]hexane-2-carboxylic acid;
(R)-1-(4-chlorobiphenyl-2-ylcarbamoyl)pyrrolidine-2-carboxylic acid;
(R)-1-(3-fluorobiphenyl-2-ylcarbamoyl)pyrrolidine-2-carboxylic acid;
(R)-1-(4-chlorobiphenyl-2-ylcarbamoyl)azetidine-2-carboxylic acid;
(R)-1-(4-(trifluoromethyl)biphenyl-2-ylcarbamoyl)pyrrolidine-2-carboxylic acid;
(R)-1-(4,6-difluorobiphenyl-2-ylcarbamoyl)pyrrolidine-2-carboxylic acid;
1-(biphenyl-2-ylcarbamoyl)-2-methylpyrrolidine-2-carboxylic acid;
(R)-1-(4-fluorobiphenyl-2-ylcarbamoyl)pyrrolidine-2-carboxylic acid;
(R)-1-(4-(trifluoromethoxy)biphenyl-2-ylcarbamoyl)pyrrolidine-2-carboxylic acid;
(R)-1-(4,6-dichlorobiphenyl-2-ylcarbamoyl)pyrrolidine-2-carboxylic acid;
(R)-1-(5′-Chloro-[1,1′;2′,1″]terphenyl-3′-ylcarbamoyl)-pyrrolidine-2-carboxylic acid;
(R)-1-(4-cyanobiphenyl-2-ylcarbamoyl)pyrrolidine-2-carboxylic acid;
(R)-1-(2-phenylbenzo[b]thiophen-3-ylcarbamoyl)pyrrolidine-2-carboxylic acid;
(R)-1-(2-phenylthieno[2,3-b]pyridin-3-ylcarbamoyl)pyrrolidine-2-carboxylic acid;
(R)-1-(6-allyl-4-chlorobiphenyl-2-ylcarbamoyl)pyrrolidine-2-carboxylic acid;
(R)-1-(2-phenylthiophen-3-ylcarbamoyl)pyrrolidine-2-carboxylic acid;
(R)-1-(4-chloro-6-cyanobiphenyl-2-ylcarbamoyl)pyrrolidine-2-carboxylic acid;
(R)-1-[4-chloro-6-(cyclohexen-1-yl)-biphenyl-2-ylcarbamoyl]pyrrolidine-2-carboxylic acid;
(S)-1-(4-chlorobiphenyl-2-ylcarbamoyl)azetidine-2-carboxylic acid;
(R)-1-(biphenyl-2-ylcarbamoyl)azetidine-2-carboxylic acid;
(R)-1-(4-chloro-4′-fluorobiphenyl-2-ylcarbamoyl)azetidine-2-carboxylic acid;
(R)-1-(4-chloro-5-fluorobiphenyl-2-ylcarbamoyl)azetidine-2-carboxylic acid;
(R)-1-(4-chloro-5-methylbiphenyl-2-ylcarbamoyl)azetidine-2-carboxylic acid;
(R)-1-(4-chloro-2′,3′-difluorobiphenyl-2-ylcarbamoyl)azetidine-2-carboxylic acid;
(R)-1-(4-chloro-2′-fluorobiphenyl-2-ylcarbamoyl)azetidine-2-carboxylic acid;
(R)-1-(4-chloro-3′-fluorobiphenyl-2-ylcarbamoyl)azetidine-2-carboxylic acid;
(R)-1-(4-chloro-3′,5′-difluorobiphenyl-2-ylcarbamoyl)azetidine-2-carboxylic acid;
(R)-1-(5-chloro-2-(thiophen-3-yl)phenylcarbamoyl)pyrrolidine-2-carboxylic acid;
(R)-1-(2-(benzo[b]thiophen-3-yl)-5-chlorophenylcarbamoyl)pyrrolidine-2-carboxylic acid;
(R)-1-(4-chloro-4′-fluorobiphenyl-2-ylcarbamoyl)pyrrolidine-2-carboxylic acid;
(R)-1-(3′,4-dichlorobiphenyl-2-ylcarbamoyl)pyrrolidine-2-carboxylic acid;
(R)-1-(3′-carbamoyl-4-chlorobiphenyl-2-ylcarbamoyl)pyrrolidine-2-carboxylic acid;
(R)-1-[5-chloro-2-(cyclohexen-1-yl)phenylcarbamoyl]pyrrolidine-2-carboxylic acid;
(R)-1-(5-chloro-2-(pyridin-4-yl)phenylcarbamoyl)pyrrolidine-2-carboxylic acid;
(R)-1-(4,4′-dichlorobiphenyl-2-ylcarbamoyl)pyrrolidine-2-carboxylic acid;
(R)-1-(4-chloro-4′-methoxybiphenyl-2-ylcarbamoyl)pyrrolidine-2-carboxylic acid;
(R)-1-(4-chloro-2′-methylbiphenyl-2-ylcarbamoyl)pyrrolidine-2-carboxylic acid;
(R)-1-(4-ethylbiphenyl-2-ylcarbamoyl)pyrrolidine-2-carboxylic acid;
(R)-1-(4-chloro-2′,4′-difluorobiphenyl-2-ylcarbamoyl)azetidine-2-carboxylic acid;
(R)-1-(4-chloro-4′-fluoro-6-methoxybiphenyl-2-ylcarbamoyl)azetidine-2-carboxylic acid;
and pharmaceutically acceptable salts thereof.

2. The compound according to claim 1 , selected from the group consisting of:
(R)-1-(4-chlorobiphenyl-2-ylcarbamoyl)azetidine-2-carboxylic acid;
(R)-1-(4-chloro-4′-fluorobiphenyl-2-ylcarbamoyl)azetidine-2-carboxylic acid;
and pharmaceutically acceptable salts thereof.

3. A pharmaceutical composition comprising a compound according to claim 1 and a therapeutically diluent, carrier or excipient.

Assignees

• Hoffmann La Roche

Inventors

• Buettelmann Bernd
• Ceccarelli Simona M
• Conte Aurelia
• Kuehne Holger
• Kuhn Bernd
• Neidhart Werner
• Sander Ulrike Obst
• Richter Hans

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

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P3/10

  for hyperglycaemia, e.g. antidiabetics · CPC title

• A61P35/00

  Antineoplastic agents · CPC title