COMPOUNDS AND METHODS FOR KINASE MODULATION, AND INDICATIONS THEREFOR

• US 20140038948A1
• Filed: 06/25/2013
• Published: 02/06/2014
• Est. Priority Date: 07/17/2007
• Status: Abandoned Application

• Current Assignee: Plexxikon Inc (Daiichi Sankyo Company Limited)
• Original Assignee: Plexxikon Inc (Daiichi Sankyo Company Limited)
• Inventors: Wu, Guoxian, Zhang, Jiazhong, Zhu, Yong-Liang, Zhang, Chao, Ibrahim, Prabha N., Shi, Songyuan, Spevak, Wayne, Artis, Dean R., Tsai, James
• Application Number:
  US13/926,959
• Publication Number:
  US 20140038948A1
• Time in Patent Office: Days
• US Class Current: 514/222.5
• CPC Class Codes: A61K 2300/00 Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
• CPC Class Codes: A61K 31/415 1,2-Diazoles
• CPC Class Codes: A61K 31/42 Oxazoles
• CPC Class Codes: A61K 31/433 Thidiazoles
• CPC Class Codes: A61K 31/437 the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
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• CPC Class Codes: A61K 31/4436 containing a heterocyclic ring having sulfur as a ring hetero atom
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• CPC Class Codes: A61K 31/444 containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
• CPC Class Codes: A61K 31/4545 containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
• CPC Class Codes: A61K 31/47 Quinolines; Isoquinolines
• CPC Class Codes: A61K 31/505 Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
• CPC Class Codes: A61K 31/506 not condensed and containing further heterocyclic rings
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• CPC Class Codes: C07D 213/74 : Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
• CPC Class Codes: C07D 213/75 : Amino or imino radicals, acylated by carboxylic or carbonic acids, or by sulfur or nitrogen analogues thereof, e.g. carbamates
• CPC Class Codes: C07D 213/76 : to which a second hetero atom is attached nitro radicals C07D213/61
• CPC Class Codes: C07D 213/82 : in position 3
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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.

Claims

1. A compound of formula (Ic):

2. The compound of claim 1, wherein R² is hydrogen.

3. The compound of claim 2, wherein R² is halogen.

4. The compound of claim 2, wherein R³ is optionally substituted phenyl.

5. The compound of claim 2, wherein R³ is phenyl optionally substituted with one or more halogen substituents.

6. The compound of claim 1, wherein R³ is phenyl optionally substituted with one or more fluoro substituents.

7. The compound of claim 6, wherein R³ is phenyl substituted with two fluoro substituents.

8. The compound of claim 1, wherein each R¹ is independently optionally substituted lower alkyl or optionally substituted heteroaryl.

9. The compound of claim 8, wherein one R¹ is lower alkyl and the other R¹ is heteroaryl substituted with one or more NH₂ groups.

10. The compound of claim 8, wherein one R¹ is lower alkyl and the other R¹ is pyrimidinyl substituted with one or more NH₂ groups.

11. The compound of claim 10, wherein one R¹ is t-butyl and the other R¹ is pyrimidinyl substituted with NH₂.

12. The compound of claim 1, wherein Ar is:

13. The compound of claim 12, wherein Ar is thiazolyl.

14. The compound of claim 12, wherein Ar is 4-thiazolyl.

16. A pharmaceutical composition comprising:

a compound of claim 1 and a pharmaceutically acceptable carrier or excipient.

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

15. A compound of formula (Ic):

17. A pharmaceutical composition comprising:

a compound of claim 15 and a pharmaceutically acceptable carrier or excipient.

19. A method for treating a subject suffering from melanoma, thyroid cancer or colorectal cancer, said method comprising:

administering to the subject an effective amount of a compound of claim 15.

20. The method of claim 19, wherein the melanoma is melanoma having a mutation encoding a V600E amino acid substitution.