Histone demethylase inhibitors

• US 9,133,166 B2
• Filed: 03/13/2014
• Issued: 09/15/2015
• 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
• Primary Examiner(s): Morris, Patricia L
• Application Number:
  US14/210,006
• Publication Number:
  US 20140275084A1
• Time in Patent Office: 551 Days
• Field of Search: 546/274.1, 514/341
• US Class Current: 1/1
• 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 R⁴ is —

CO₂H.

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

CO₂R⁶.

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

C(O)N(H)CN.

5. The compound of claim 1, wherein R² is C1-C5alkyl.

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

7. The compound of claim 1, wherein R² is C1-C5alkyl substituted with (C1-C5alkyl)-O—

.

8. The compound of claim 1, wherein R² is C1-C5alkyl substituted with (C1-C5alkyl)₂N—

.

9. The compound of claim 1, wherein R² is C1-C5alkyl substituted with (C6-C10aryl)(C1-C5alkyl)amino.

10. The compound of claim 1, wherein R² is C1-C5alkyl substituted with (C3-C8cycloalkyl)(C1-C5alkyl)amino.

11. The compound of claim 1, wherein R² is C1-C5alkyl substituted with (C6-C10ar(C1-C5alkylene))(C1-C5alkyl)amino.

12. The compound of claim 1, wherein R² is C1-C5alkyl substituted with (C3-C8cycloalkyl(C1-C5alkylene))(C1-C5alkyl)amino.

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

14. The compound of claim 1, wherein R¹ is C6-C10aryl.

15. The compound of claim 14, wherein R¹ is phenyl optionally substituted with one or more groups selected from halogen, —

OH, —

OR⁵, —

N(R⁵)₂, —

CON(R⁵)₂, C1-C5alkyl, C2-C5alkynyl, C3-C8cycloalkyl, C6-C10aryl, C3-C8cycloalkyl(C1-C5alkylene), and (C6-C10ar(C1-C5alkylene).

16. The compound of claim 14, wherein R¹ is phenyl optionally substituted with one or more groups selected from halogen, —

OH, —

OR⁵, C1-C5alkyl, and C3-C8cycloalkyl.

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