Benzimidazole derivatives: preparation and pharmaceutical applications

Patent metadata

Field	Value
Publication number	US-9402829-B2
Application number	US-201514627418-A
Country	US
Kind code	B2
Filing date	Feb 20, 2015
Priority date	Sep 22, 2003
Publication date	Aug 2, 2016
Grant date	Aug 2, 2016

First claim

What is claimed is:

1. A method of treating colon cancer, ovarian cancer, prostate cancer, breast cancer, lung cancer, liver cancer, pancreatic cancer, renal cancer, sarcoma, neuroblastoma, gastric cancer, multiple myeloma, myeloproliferative neoplasms, or hematologic cancers in a patient, the method comprising administering to the patient a therapeutically effective amount of a compound of formula:

wherein
R 1 is selected from the group consisting of: C 1 -C 10 alkyl, alkenyl, alkynyl, heteroalkyl, cycloalkyl, heterocycloalkyl, cycloalkylalkyl, C 4 -C 9 heterocycloalkylalkyl, each of which may be unsubstituted or substituted with one or more substituents independently selected from the group consisting of: alkylamino, acylamino, and aminoalkyl;
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, 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, aryl sulfonyl, 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.

2. The method according to claim 1 , wherein R 3 =H.

3. The method according to claim 1 , wherein X and Y=H.

4. The method according to claim 1 , wherein R 1 is selected from the group consisting of: C 1 -C 10 alkyl and heterocycloalkyl, each of which may be unsubstituted or substituted as defined in claim 1 .

5. The method of claim 1 , wherein R 1 is selected from the group consisting of: 2-(morpholin-4-yl)-ethyl; 2-(piperidin-1-yl)-ethyl; 2-(pyrrolidin-1-yl)-ethyl; 2-diethylamino-ethyl; propyl; 2,2-dimethyl-propyl; 3-dimethylamino-propyl; 3-dimethylamino-2,2-dimethyl-propyl; 3-(morpholin-4-yl)-propyl; 3-(4-methyl-piperazin-1-yl)-propyl; 3-(pyrrolidin-1-yl)-propyl; and 4-dimethylamino-butyl.

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

7. The method according to claim 1 , wherein R 2 is selected from the group consisting of 2-phenyl-propyl, 2-phenyl-ethyl, (4-fluoro-phenyl)-ethyl, (3-methoxy-phenyl)-ethyl, and 2-pyridin-3-yl-ethyl.

8. The method according to claim 1 , wherein R 2 is selected from the group consisting of methyl, ethyl, n-propyl, 2-propyl, n-butyl, sec-butyl, isobutyl, t-butyl, hexyl, and octyl.

Assignees

• Mei Pharma Inc

Inventors

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

Classifications

• A61P43/00

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

• A61P37/06

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

• A61P9/00

  Drugs for disorders of the cardiovascular system · CPC title

• A61P9/04

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

• A61P37/02

  Immunomodulators · CPC title