Benzimidazole derivatives: preparation and pharmaceutical applications

Patent metadata

Field	Value
Publication number	US-2016279102-A1
Application number	US-201615178742-A
Country	US
Kind code	A1
Filing date	Jun 10, 2016
Priority date	Sep 22, 2003
Publication date	Sep 29, 2016
Grant date	—

First claim

What is claimed is:

1 . A method of treatment of a disorder selected from the group consisting of inflammatory disorders, immune system disorders, cardiovascular diseases, fibrotic diseases, vascular diseases, viral diseases, neurological diseases, parasitic diseases and proliferative disorders, the method comprising administering a therapeutically effective amount of a compound of formula:

wherein
R 1 is selected from the group consisting of: H, and unsubstituted or substituted C 1 -C 10 alkyl, alkenyl, alkynyl, haloalkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkylalkyl, C 4 -C 9 heterocycloalkylalkyl, arylalkyl, and heteroarylalkyl, each of which may be unsubstituted or substituted with one or more substituents independently selected from the group consisting of: halogen, ═O, ═S, —CN, —NO 2 , alkyl, alkenyl, alkynyl, haloalkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, hydroxy, hydroxyalkyl, alkoxy, alkoxyalkyl, alkylamino, acylamino, aminoalkyl, phenoxy, benzyloxy, alkylsulfonyl, arylsulfonyl, aminosulfonyl, —COOH, —C(O)OR 5 , —SH, - and acyl;
R 2 is selected from the group consisting of: H, halogen, and unsubstituted or substituted C 1 -C 10 alkyl, alkenyl, alkynyl, haloalkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, cycloalkylalkyl, C 4 -C 9 heterocycloalkylalkyl, arylalkyl, and heteroarylalkyl, each of which may be unsubstituted or substituted with one or more substituents independently selected from the group consisting of: halogen, ═O, ═S, —CN, —NO 2 , alkyl, alkenyl, alkynyl, haloalkyl, heteroalkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, hydroxy, hydroxyalkyl, alkoxy, alkoxyalkyl, phenoxy, benzyloxy, alkylamino, acylamino, aminoalkyl, alkylsulfonyl, arylsulfonyl, aminosulfonyl, —COOH, —C(O)OR 5 , —SH, and acyl;
R 3 is selected from the group consisting of H, C 1 -C 6 alkyl, and acyl;
X and Y are the same or different and are independently selected from the group consisting of: H, halogen, —CN, —NO 2 , —CF 3 , C 1 -C 4 alkyl, —COR 5 , —SR 6 , —OR 6 , and —NR 7 R 8 ;
R 5 is C 1 -C 4 alkyl;
R 6 is C 1 -C 4 alkyl;
R 7 and R 8 are each independently selected from the group consisting of: H, C 1 -C 4 alkyl, C 4 -C 9 cycloalkyl, C 4 -C 9 heterocycloalkyl, aryl, heteroaryl, arylalkyl and heteroarylalkyl;
or a pharmaceutically acceptable salt thereof,
to a patient in need thereof.

2 . A method according to claim 1 wherein in the compound, R 3 ═H.

3 . A method according to claim 1 wherein in the compound, X and Y═H.

4 . A method according to claim 1 wherein in the compound R 1 is selected from the group consisting of H, and unsubstituted or substituted hydroxyalkyl, C 1 -C 10 alkyl, heteroalkyl, arylalkyl, heteroarylalkyl, and heterocycloalkyl, each of which may be unsubstituted or substituted as defined in claim 1 .

5 . A method according to claim 1 wherein in the compound R 1 is selected from the group consisting of H, methyl; (pyridin-3-yl)methyl; 2-hydroxy-ethyl; 2,3-di-hydroxy-propyl; and 3-hydroxy-propyl.

6 . A method according to claim 1 wherein in the compound R 2 is selected from the group consisting of H, and unsubstituted or substituted C 1 -C 10 alkyl, arylalkyl, aryl, heteroaryl, heteroalkyl, and cycloalkyl, each of which may be unsubstituted or substituted as defined in claim 1 .

7 . A method according to claim 1 wherein in the compound R 2 is selected from the group consisting of 2-phenyl-propyl, 2-phenyl-ethyl, 4-methoxy-phenyl, 4-benzyloxy-3-methoxy-phenyl, pyridin-2-yl, and pyridin-4-yl.

8 . A method of claim 1 wherein the compound is selected from compounds, and their pharmaceutically acceptable salts, selected from the group consisting of

9 . A method of claim 1 wherein the compound is selected from compounds, and their pharmaceutically acceptable salts, selected from the group consisting of

10 . A method according to claim 1 wherein in the compound R′ is selected from the group consisting of: 2-(piperidin-1-yl)-ethyl; 2-(pyrrolidin-1-yl)-ethyl; 2-diethylamino-ethyl; and 3-dimethylamino-2,2-dimethyl-propyl.

11 . A method according to claim 1 wherein the disorder is a inflammatory disorder or an autoimmune disorder selected from the group consisting of Rheumatoid arthritis, Osteoarthritis, Juvenile chronic arthritis, Graft vs host disease, Asthma, Psoriasis, Ankylosing spondylitis, Crohn's diseases Inflammatory bowel disease, Lupus erythematosus and Chronic bronchitis

12 . A method according to claim 1 wherein the disorder is atherosclerosis.

13 . A method according to claim 1 wherein the disorder is a fibrotic disease.

14 . A method according to claim 14 wherein the fibrotic disease is liver fibrosis.

15 . A method according to claim 1 wherein the d

Assignees

• Mei Pharma Inc

Inventors

• Chen Dizhong
• Song Hong Yan
• Sun Eric T
• Yu Niefang
• Zou Yong

Classifications

• A61P9/04

  Inotropic agents, i.e. stimulants of cardiac contraction; Drugs for heart failure · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · CPC title

• A61P37/06

  Immunosuppressants, e.g. drugs for graft rejection · CPC title

• A61P43/00

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

• A61P37/02

  Immunomodulators · CPC title