HISTONE DEMETHYLASE INHIBITORS

• US 20140194469A1
• Filed: 12/05/2013
• Published: 07/10/2014
• Est. Priority Date: 12/06/2012
• Status: Active Grant

• Current Assignee: Celgene Quanticel Research, Inc. (Bristol-Myers Squibb Company)
• Original Assignee: Quanticel Pharmaceuticals, Inc. (Bristol-Myers Squibb Company)
• Inventors: Nie, Zhe, Stafford, Jeffrey Alan, Veal, James Marvin, Wallace, Michael Brennen
• Granted Patent: US 8,987,461 B2
• Time in Patent Office: Days
• US Class Current: 514/333
• CPC Class Codes: A61K 31/44 Non condensed pyridines; Hydrogenated derivatives thereof
• CPC Class Codes: A61K 31/4439 containing a five-membered ring with nitrogen as a ring hetero atom, e.g. omeprazole nicotine A61K31/465
• CPC Class Codes: A61K 31/444 containing a six-membered ring with nitrogen as a ring heteroatom, e.g. amrinone
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: A61P 43/00 Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
• CPC Class Codes: C07D 401/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C07D 405/14 containing three or more hetero rings

Abstract

Provided herein are substituted pyrazolylpyridine, pyrazolylpyridazine, and pyrazolylpyrimidine derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition histone demethylase. Furthermore, the subject compounds and compositions are useful for the treatment of cancer, such as prostate cancer, breast cancer, bladder cancer, lung cancer and/or melanoma and the like.

Claims

1. A compound of Formula (II), or a pharmaceutically acceptable salt thereof,

2. The compound or pharmaceutically acceptable salt of claim 1, wherein R⁴ is hydrogen.

3. The compound or pharmaceutically acceptable salt of claim 1, wherein R⁴ is alkyl.

4. The compound or pharmaceutically acceptable salt of claim 1, wherein R¹ or R² is alkyl.

5. The compound or pharmaceutically acceptable salt of claim 1, wherein R¹ or R² is carbocyclyl.

6. The compound or pharmaceutically acceptable salt of claim 1, wherein R¹ or R² is aryl.

7. The compound or pharmaceutically acceptable salt of claim 1, wherein R¹ or R² is aralkyl.

8. A compound of Formula (IV) or a pharmaceutically acceptable salt thereof,

9. The compound or pharmaceutically acceptable salt of claim 8, wherein R⁴ is hydrogen.

10. The compound or pharmaceutically acceptable salt of claim 8, wherein R⁴ is alkyl.

11. The compound or pharmaceutically acceptable salt of claim 8, wherein R¹ and R² are hydrogen.

12. The compound or pharmaceutically acceptable salt of claim 8, wherein X is C₁-C₄ alkylene.

13. The compound or pharmaceutically acceptable salt of claim 8, wherein X is C₁-C₂ alkylene.

14. The compound or pharmaceutically acceptable salt of claim 8, wherein X is C₁ alkylene.

15. The compound or pharmaceutically acceptable salt of claim 8, wherein Y is hydrogen.

16. The compound or pharmaceutically acceptable salt of claim 8, wherein Y is carbocyclyl.

17. The compound or pharmaceutically acceptable salt of claim 8, wherein Y is aryl.

18. The compound or pharmaceutically acceptable salt of claim 8, wherein Y is a phenyl.

19. The compound or pharmaceutically acceptable salt of claim 8, wherein Y is heteroaryl.

20. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound Formula (II) or a pharmaceutically acceptable salt thereof.

21. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound Formula (IV) or a pharmaceutically acceptable salt thereof.

22. A method for inhibiting a histone-demethylase enzyme comprising contacting a histone demethylase enzyme with a compound of Formula (II).

23. A method for inhibiting a histone-demethylase enzyme comprising contacting a histone demethylase enzyme with a compound of Formula (IV).

24. A method for treating cancer in subject comprising administering to the subject in need thereof a composition comprising a compound of Formula (II) or pharmaceutically acceptable salt thereof.

25. A method for treating cancer in subject comprising administering to the subject in need thereof a composition comprising a compound of Formula (IV) or pharmaceutically acceptable salt thereof.