IP Library › Patent Application 14968763

Patent Application

App. No. 14/968,763

BENZOIMIDAZOLES AS PROLYL HYDROXYLASE INHIBITORS

Loading inventors, assignments & file history…

Monitor This Case

Get email alerts when status or documents change.

Order Certified Copies

Most orders are placed with the USPTO same day — all within 24 business hours.

Order via The Patent Place →

Pre-filled with this patent's details

Quick Facts

Patent No.: US None
App. No.: 14/968,763

External Links

USPTO Patent Center↗ Full Patent PDF↗

Abstract

The present invention is directed to benzoimidazole compounds of the formula: and enantiomers, diastereomers, racemates, and pharmaceutically acceptable salts thereof. Compounds of the present invention are useful in pharmaceutical compositions and methods for the treatment of disease states, disorders, and conditions modulated by prolyl hydroxylase activity.

Claims (120)

1 . A compound having PHD inhibitor activity of the formula (I):

wherein:

n is 2-4;

each R 1 is independently selected from: H, halo, —C 1-4 alkyl, —C 1-4 perhaloalkyl, trifluoroC 1-4 alkoxy, —NO 2 , —CN, —OC 1-4 alkyl, —S—R c , —SO 2 —R c and —NR a R b ;

R a and R b are each independently H;

R c is phenyl optionally substituted with R d ;

each R d is independently selected from the group consisting of: —H, halo, —C 1-4 alkyl or —C 1-4 perhaloalkyl, trifluoroC 1-4 alkoxy, and —OC 1-4 alkyl;

R 2 and R 3 are selected from: H, —CF 3 , or C 1-3 alkyl; and

each Z is C and

enantiomers, diastereomers, racemates, and pharmaceutically acceptable salts thereof.

2 . A compound of claim 1 , where R 2 and R 3 are each —H.

3 . A compound of claim 1 wherein each R 1 is independently selected from the group consisting of: H, halo, —CF 3 , —OCF 3 , benzylsulfanyl optionally substituted or unsubstituted with up to three halo, C 1-4 alkyl, —CF 3 , and —OCF 3 , and benzenesulfonyl optionally substituted or unsubstituted with up to three C 1-4 alkyl, C 1-4 alkoxy, halo, —CF 3 , and —OCF 3 .

4 . (canceled)

5 . (canceled)

6 . A compound of claim 1 , wherein each R 1 is independently selected from: H, halo, —C 1-4 alkyl, —CF 3 , —OCF 3 , —NO 2 , —NH 2 —CN, and —OC 1-4 alkyl.

7 . The compound of claim 1 , wherein said compound is selected from the group consisting of:

1-(5,6-Dichloro-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylic acid;

1-(5-Chloro-6-fluoro-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylic acid;

1-(5,6-Dimethyl-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylic acid;

1-(5,6-Dichloro-1H-benzoimidazol-2-yl)-3-trifluoromethyl-1H-pyrazole-4-carboxylic acid;

1-(5,6-Dichloro-1H-benzoimidazol-2-yl)-3,5-dimethyl-1H-pyrazole-4-carboxylic acid;

1-(6-Chloro-5-trifluoromethyl-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylic acid;

1-(5,6-Difluoro-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylic acid;

1-(6-Chloro-5-cyano-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylic acid;

1-(6-Chloro-5-nitro-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylic acid;

1-(5-Amino-6-chloro-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylic acid;

1-(6-Chloro-5-methoxy-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylic acid;

1-(6-Chloro-5-m-tolylsulfanyl-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylic acid;

1-[6-Chloro-5-(4-chloro-phenylsulfanyl)-1H-benzoimidazol-2-yl]-1H-pyrazole-4-carboxylic acid;

1-(6-Chloro-5-phenylsulfanyl-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylic acid;

1-[6-Chloro-5-(3,4-dichloro-phenylsulfanyl)-1H-benzoimidazol-2-yl]-1H-pyrazole-4-carboxylic acid;

1-[6-Chloro-5-(toluene-3-sulfonyl)-1H-benzoimidazol-2-yl]-1H-pyrazole-4-carboxylic acid;

1-(5-Benzenesulfonyl-6-chloro-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylic acid;

1-[6-Chloro-5-(4-methoxy-benzenesulfonyl)-1H-benzoimidazol-2-yl]-1H-pyrazole-4-carboxylic acid;

1-[6-Chloro-5-(4-chloro-benzenesulfonyl)-1H-benzoimidazol-2-yl]-1H-pyrazole-4-carboxylic acid;

1-[6-Chloro-5-(4-trifluoromethoxy-benzenesulfonyl)-1H-benzoimidazol-2-yl]-1H-pyrazole-4-carboxylic acid;

1-[6-Chloro-5-(3,4-dichloro-benzenesulfonyl)-1H-benzoimidazol-2-yl]-1H-pyrazole-4-carboxylic acid;

1-(6-Bromo-5-fluoro-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylic acid;

1-(6-Chloro-5-trifluoromethoxy-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylic acid;

1-(6-Ethoxy-5-fluoro-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylic acid;

1-(5,6-Bis-trifluoromethyl-1H-benzoimidazol-2-yl)-1H-pyrazole-4-carboxylic acid;

1-(6-Fluoro-5-trifluoromethyl-1H-benzimidazol 2-yl)-1H-pyrazole-4 carboxylic acid;

and pharmaceutically acceptable salts thereof.

8 . A pharmaceutical composition comprising a pharmaceutically acceptable excipient and an effective amount of compound having PHD inhibitor activity of formula (I):