Certain protein kinase inhibitors

Patent metadata

Field	Value
Publication number	US-10328060-B2
Application number	US-201515523315-A
Country	US
Kind code	B2
Filing date	Nov 1, 2015
Priority date	Nov 1, 2014
Publication date	Jun 25, 2019
Grant date	Jun 25, 2019

Abstract

Provided are certain PI3K inhibitors, pharmaceutical compositions thereof, and methods of use therefor.

First claim

What is claimed is:

1. A compound of formula (I):

or a pharmaceutically acceptable salt thereof, wherein:
A-B is a 5-6 membered fused pyridone ring system, which is:

W is

R 1 is selected from aryl, aryl-C 1-4 alkyl, heteroaryl, and heteroaryl-C 1-4 alkyl, wherein aryl and heteroaryl are each unsubstituted or substituted with at least one substituent independently selected from R 6a ;
R 2 is selected from hydrogen, C 1-10 alkyl, C 3-10 cycloalkyl, C 3-10 cycloalkyl-C 1-4 alkyl, heterocyclyl, and heterocyclyl-C 1-4 alkyl, wherein alkyl, cycloalkyl, and heterocyclyl are each unsubstituted or substituted with at least one substituent independently selected from R 6a ;
R 3 is selected from hydrogen, C 1-10 alkyl, and C 3-10 cycloalkyl, wherein alkyl and cycloalkyl are each unsubstituted or substituted with at least one substituent independently selected from R 6a ;
R 4 is selected from hydrogen, halogen, cyano, C 1-10 alkyl, C 3-10 cycloalkyl, and C 3-10 cycloalkyl-C 1-4 alkyl, wherein alkyl and cycloalkyl are each unsubstituted or substituted with at least one substituent independently selected from R 6a ;
each R 5 is independently selected from hydrogen, halogen, CF 3 , C 1-10 alkyl, and C 3-10 cycloalkyl, wherein alkyl and cycloalkyl are each unsubstituted or substituted with at least one substituent independently selected from R 6a ;
each R 6a is independently selected from C 1-10 alkyl, C 3-10 cycloalkyl, C 3-10 cycloalkyl-C 1-4 alkyl, OR 8 , NO 2 , halogen, SR 8 , NR 7 R 8 , and CN;
each R 7 and each R 8 are independently selected from hydrogen and C 1-10 alkyl;
m is independently selected from 0, 1, and 2.

2. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein A-B is

3. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 5 is selected from hydrogen, halogen, C 1-6 alkyl, CF 3 , and cyclopropyl.

4. The compound of claim 3 or a pharmaceutically acceptable salt thereof, wherein R 5 is selected from hydrogen, chloro, methyl, ethyl, CF 3 , and cyclopropyl.

5. The compound of claim 4 or a pharmaceutically acceptable salt thereof, wherein R 5 is selected from chloro, methyl and CF 3 .

6. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 1 is aryl which is unsubstituted or substituted with at least one substituent independently selected from R 6a .

7. The compound of claim 6 or a pharmaceutically acceptable salt thereof, wherein R 1 is phenyl, which is unsubstituted or substituted with at least one substituent independently selected from R 6a .

8. The compound of claim 7 or a pharmaceutically acceptable salt thereof, wherein R 1 is phenyl, which is unsubstituted or substituted with fluoro.

9. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 2 is selected from C 1-10 alkyl and C 3-10 cycloalkyl, wherein alkyl and cycloalkyl are unsubstituted or substituted with at least one substituent independently selected from R 6a .

10. The compound of claim 9 or a pharmaceutically acceptable salt thereof, wherein R 2 is selected from methyl, ethyl, isopropyl and cyclopropyl.

11. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 3 is hydrogen.

12. The compound of claim 1 or a pharmaceutically acceptable salt thereof, wherein R 4 is hydrogen.

13. The compound of claim 1 , selected from
2-amino-4-methyl-6-((1-(3-methyl-5-oxo-6-phenyl-5H-thiazolo[3,2-c]pyridin-7-yl)ethyl)amino)pyrimidine-5-carbonitrile,
2-amino-4-((1-(3-chloro-6-(3-fluorophenyl)-5-oxo-5H-thiazolo[3,2-c]pyridin-7-yl)ethyl)amino)-6-methylpyrimidine-5-carbonitrile,
or a pharmaceutically acceptable salt thereof.

14. A pharmaceutical composition, comprising a compound claim 1 or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable carrier.

15. A compound of claim 7 or a pharmaceutically acceptable salt thereof, wherein R 1 is phenyl which is unsubstituted or substituted with at least one substituent independently selected from halogen.

Assignees

• Shanghai Fochon Pharmaceutical Co Ltd
• Shanghai Inst Materia Medica Cas
• Chongqing Fochon Pharmaceutical Co Ltd

Inventors

• Zhao Xingdong
• Ding Jian
• Meng Linghua
• Geng Meiyu
• Li Tongshuang
• Zhou Zuwen
• Chen Ling
• Liu Qihong
• Wang Xianlong
• Yang Lijun
• Rong Yue
• Tan Rui
• Yu Chuiliang
• Jiang Lihua
• Liu Yanxin
• Linghu Li
• Sun Jing
• Wang Weibo

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

• A61P35/00

  Antineoplastic agents · CPC title

• A61P31/00

  Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics · CPC title