Benzimidazole derivatives: preparation and pharmaceutical applications

Patent metadata

Field	Value
Publication number	US-10201527-B2
Application number	US-201715612670-A
Country	US
Kind code	B2
Filing date	Jun 2, 2017
Priority date	Sep 22, 2003
Publication date	Feb 12, 2019
Grant date	Feb 12, 2019

First claim

What is claimed is:

1. A method of treating hematologic malignancies 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, 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 each 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 of 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 of 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.

9. The method of claim 1 , wherein the hematologic malignancy is selected from leukemia, acute lymphocytic leukemia, acute myeloid leukemia, chronic lymphocytic leukemia, chronic myeloid leukemia, hairy cell leukemia, acute promyelocytic leukemia, plasma cell leukemia, myeloma, myelodysplastic syndromes, and myeloproliferative disorders.

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

• A61P37/02

  Immunomodulators · CPC title

• A61P37/00

  Drugs for immunological or allergic disorders · 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