HISTONE DEMETHYLASE INHIBITORS

• US 20140275084A1
• Filed: 03/13/2014
• Published: 09/18/2014
• Est. Priority Date: 03/14/2013
• Status: Active Grant

• Current Assignee: Celgene Quanticel Research, Inc. (Bristol-Myers Squibb Company)
• Original Assignee: Quanticel Pharmaceuticals, Inc. (Bristol-Myers Squibb Company)
• Inventors: Kanouni, Toufike, Nie, Zhe, Stafford, Jeffrey Alan, Veal, James Marvin
• Granted Patent: US 9,133,166 B2
• Time in Patent Office: Days
• US Class Current: 514/235.8
• CPC Class Codes: A61K 31/00 Medicinal preparations containing organic active ingredients
• 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: A61K 31/4545 containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
• CPC Class Codes: A61K 31/4709 Non-condensed quinolines and containing further heterocyclic rings
• CPC Class Codes: A61K 31/5377 not condensed and containing further heterocyclic rings, e.g. timolol
• 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
• CPC Class Codes: C07D 413/14 containing three or more hetero rings

Abstract

The present invention relates generally to compositions and methods for treating cancer and neoplastic diseases. Provided herein are substituted imidazole-pyridine derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition of histone demethylase enzymes. 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 having the structure of Formula (II):

2. The compound of claim 1, wherein R³ is hydrogen.

3. The compound of claim 1, wherein R⁴ is —

CO₂H.

4. The compound of claim 1, wherein R⁴ is —

CO₂R⁶.

5. The compound of claim 1, wherein R⁴ is —

C(O)N(H)CN.

6. The compound of claim 1, wherein R⁴ is tetrazolyl.

7. The compound of claim 1, wherein R² is alkyl.

8. The compound of claim 1, wherein R² is methyl.

9. The compound of claim 1, wherein R² is alkyl substituted with alkoxy.

10. The compound of claim 1, wherein R² is alkyl substituted with dialkylamino.

11. The compound of claim 1, wherein R² is alkyl substituted with (aryl)(alkyl)amino.

12. The compound of claim 1, wherein R² is alkyl substituted with (carbocyclyl)(alkyl)amino.

13. The compound of claim 1, wherein R² is alkyl substituted with (heteroaryl)(alkyl)amino.

14. The compound of claim 1, wherein R² is alkyl substituted with (heterocyclyl)(alkyl)amino.

15. The compound of claim 1, wherein R² is alkyl substituted with (aralkyl)(alkyl)amino.

16. The compound of claim 1, wherein R² is alkyl substituted with (carbocyclylalkyl)(alkyl)amino.

17. The compound of claim 1, wherein R² is alkyl substituted with (heteroarylalkyl)(alkyl)amino.

18. The compound of claim 1, wherein R² is alkyl substituted with (heterocyclylalkyl)(alkyl)amino.

19. The compound of claim 1, wherein R² is heterocyclyl.

20. The compound of claim 1, wherein R² is heterocyclylalkyl.

21. The compound of claim 1, wherein R² is heteroaryl.

22. The compound of claim 1, wherein R² is heteroarylalkyl.

23. The compound of claim 1, wherein R¹ is hydrogen.

24. The compound of claim 1, wherein R¹ is aryl.

25. The compound of claim 24, wherein R¹ is phenyl optionally substituted with one or more groups selected from halogen, —

OH, —

OR⁵, —

N(R⁵)₂, —

CON(R⁵)₂, alkyl, alkynyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, carbocyclylalkyl, heterocyclylalkyl, aralkyl, and heteroarylalkyl.

26. The compound of claim 24, wherein R¹ is phenyl optionally substituted with one or more groups selected from halogen, —

OH, —

OR⁵, alkyl, carbocyclyl, heterocyclyl, and heteroaryl.

27. A pharmaceutical composition comprising a compound of claim 1, or a pharmaceutically acceptable salt thereof, and at least one pharmaceutically acceptable excipient.

28. A method for inhibiting a histone demethylase comprising contacting the histone demethylase enzyme with a compound of claim 1.

29. A method for treating cancer in a subject comprising administering to the subject in need thereof a composition comprising a compound of claim 1, or a pharmaceutically acceptable salt thereof.