Compounds and methods for kinase modulation, and indications therefor

Patent metadata

Field	Value
Publication number	US-9844539-B2
Application number	US-201615260042-A
Country	US
Kind code	B2
Filing date	Sep 8, 2016
Priority date	Jul 17, 2007
Publication date	Dec 19, 2017
Grant date	Dec 19, 2017

Abstract

Compounds active on protein kinases are described, as well as methods of using such compounds to treat diseases and conditions associated with aberrant activity of protein kinases.

First claim

What is claimed is:

1. A compound of formula (Ia):

or a pharmaceutically acceptable salt thereof,
wherein:
L 1 is a bond or —N(H)C(O)—;
each R 1 is optionally substituted lower alkyl or optionally substituted heteroaryl;
R 2 is hydrogen or halogen;
R 4 is hydrogen;
R 3 is optionally substituted lower alkyl or optionally substituted aryl;
m is 0, 1, 2, or 3; and
Ar is a monocyclic heteroaryl containing 5 to 6 atoms wherein at least one atom is nitrogen.

2. The compound of claim 1 , wherein R 2 is hydrogen.

3. The compound of claim 1 , wherein R 2 is halogen.

4. The compound of claim 1 , wherein R 3 is optionally substituted phenyl.

5. The compound of claim 1 , wherein R 3 is phenyl substituted with one or more substituents selected from the group consisting of fluoro, lower alkyl, fluoro substituted lower alkyl, lower alkoxy, fluoro substituted lower alkoxy, lower alkylthio, and fluoro substituted lower alkylthio.

6. The compound of claim 1 , wherein R 3 is phenyl substituted with one or more fluoro.

7. The compound of claim 1 , wherein one of the R 1 substituents is optionally substituted lower alkyl containing 1-4 carbon atoms.

8. The compound of claim 1 , wherein one of the R 1 substituents is optionally substituted heteroaryl.

9. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier or excipient.

10. A pharmaceutical composition comprising a compound of claim 1 and another therapeutic agent.

11. A compound of formula (Ia):

or a pharmaceutically acceptable salt thereof,
wherein:
L 1 is a bond;
each R 1 is optionally substituted lower alkyl or optionally substituted heteroaryl;
R 2 is hydrogen or halogen;
R 4 is hydrogen;
R 3 is optionally substituted lower alkyl or optionally substituted aryl;
m is 0, 1, 2, 3, 4, or 5; and
Ar is a monocyclic heteroaryl containing 5 to 6 atoms wherein at least one atom is nitrogen.

12. The compound of claim 11 , wherein R 2 is hydrogen.

13. The compound of claim 11 , wherein R 2 is halogen.

14. The compound of claim 11 , wherein R 3 is optionally substituted phenyl.

15. The compound of claim 11 , wherein R 3 is phenyl substituted with one or more substituents selected from the group consisting of fluoro, lower alkyl, fluoro substituted lower alkyl, lower alkoxy, fluoro substituted lower alkoxy, lower alkylthio, and fluoro substituted lower alkylthio.

16. The compound of claim 11 , wherein R 3 is phenyl substituted with one or more fluoro.

17. The compound of claim 11 , wherein one of the R 1 substituents is optionally substituted lower alkyl containing 1-4 carbon atoms.

18. The compound of claim 11 , wherein one of the R 1 substituents is optionally substituted heteroaryl.

19. A pharmaceutical composition comprising a compound of claim 11 and a pharmaceutically acceptable carrier or excipient.

20. A pharmaceutical composition comprising a compound of claim 11 and another therapeutic agent.

21. A compound of formula (Ia):

or a pharmaceutically acceptable salt thereof,
wherein:
L 1 is —N(H)C(O)—;
each R 1 is optionally substituted lower alkyl or optionally substituted heteroaryl;
R 2 is hydrogen or halogen;
R 4 is hydrogen;
R 3 is optionally substituted lower alkyl or optionally substituted aryl;
m is 0, 1, 2, 3, 4, or 5; and
Ar is a monocyclic heteroaryl containing 5 to 6 atoms wherein at least one atom is nitrogen.

22. The compound of claim 21 , wherein R 2 is hydrogen.

23. The compound of claim 21 , wherein R 2 is halogen.

24. The compound of claim 21 , wherein R 3 is optionally substituted phenyl.

25. The compound of claim 21 , wherein R 3 is phenyl substituted with one or more substituents selected from the group consisting of fluoro, lower alkyl, fluoro substituted lower alkyl, lower alkoxy, fluoro substituted lower alkoxy, lower alkylthio, and fluoro substituted lower alkylthio.

26. The compound of claim 21 , wherein R 3 is phenyl substituted with one or more fluoro.

27. The compound of claim 21 , wherein one of the R 1 substituents is optionally substituted lower alkyl containing 1-4 carbon atoms.

28. The compound of claim 21 , wherein one of the R 1 substituents is optionally substituted heteroaryl.

29. A pharmaceutical composition comprising a compound of claim 21 and a pharmaceutically acceptable carrier or excipient.

30. A pharmaceutical composition comprising a compound of claim 21 and another therapeutic agent.

Assignees

• Plexxikon Inc

Inventors

• Wu Guoxian
• Zhang Jiazhong
• Zhu Yong-Liang
• Zhang Chao
• Ibrahim Prabha N
• Shi Songyuan
• Spevak Wayne
• Artis Dean R
• Tsai James

Classifications

• A61P5/14

  of the thyroid hormones, e.g. T3, T4 · CPC title

• A61P43/00

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

• A61P3/06

  Antihyperlipidemics · CPC title

• A61P37/06

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

• A61P5/00

  Drugs for disorders of the endocrine system · CPC title