HISTONE DEMETHYLASE INHIBITORS

• US 20140213591A1
• Filed: 12/23/2013
• Published: 07/31/2014
• Est. Priority Date: 12/21/2012
• 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, Wallace, Michael Brennan, Chen, Young K.
• Granted Patent: US 8,952,151 B2
• Time in Patent Office: Days
• US Class Current: 514/247
• 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 213/74 Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
• CPC Class Codes: C07D 213/79 Acids; Esters
• CPC Class Codes: C07D 213/81 Amides; Imides
• CPC Class Codes: C07D 237/24 Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
• CPC Class Codes: C07D 401/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 401/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 405/14 containing three or more hetero rings
• CPC Class Codes: C07D 409/12 linked by a chain containing hetero atoms as chain links
• CPC Class Codes: C07D 409/14 containing three or more hetero rings

Abstract

The present invention relates generally to compositions and methods for treating cancer and neoplastic disease. Provided herein are substituted amidopyridine or amidopyridazine 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 (XI), or a pharmaceutically acceptable salt thereof,

4. The compound, or pharmaceutically acceptable salt thereof, of any one of claims 1-3, wherein Q is —

CO₂R, and R is hydrogen.

5. The compound, or pharmaceutically acceptable salt thereof, of any one of claims 1-3, wherein Q is —

C(O)N(H)CN.

6. The compound, or pharmaceutically acceptable salt thereof, of any one of claims 1-3, wherein Q is —

C(O)N(H)OH.

7. The compound, or pharmaceutically acceptable salt thereof, of any one of claims 1-3, wherein Q is tetrazolyl.

9. The compound, or pharmaceutically acceptable salt thereof, of any one of claims 1-3, wherein Q is —

CO₂R and R is optionally substituted alkyl.

10. The compound, or pharmaceutically acceptable salt thereof, of claim 1, wherein Y is optionally substituted tetralinyl.

11. The compound, or pharmaceutically acceptable salt thereof, of claim 1, wherein Y is optionally substituted tetrahydroquinolinyl.

12. The compound, or pharmaceutically acceptable salt thereof, of claim 1, wherein Y is substituted pyridyl.

13. The compound, or pharmaceutically acceptable salt thereof, of claim 1, wherein Y is optionally substituted naphthyl.

14. The compound, or pharmaceutically acceptable salt thereof, of claim 1, wherein Y is optionally substituted indolyl.

15. The compound, or pharmaceutically acceptable salt thereof, of claim 1, wherein Y is optionally substituted benzofuranyl.

16. The compound, or pharmaceutically acceptable salt thereof, of claim 1, wherein Y is optionally substituted adamantyl.

17. The compound, or pharmaceutically acceptable salt thereof, of claim 1, wherein Y is optionally substituted indanyl.

19. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of claim 1, 2, 3, or 18, or a pharmaceutically acceptable salt thereof.

20. A method of inhibiting a histone demethylase enzyme comprising contacting the histone demethylase enzyme with a compound of claim 1, 2, 3, or 18, or a pharmaceutically acceptable salt thereof.

21. A method of treating cancer in a subject in need thereof comprising administering to the subject a composition comprising a compound of claim 1, 2, 3, or 18, or a pharmaceutically acceptable salt thereof.

2. A compound of Formula (XI), or a pharmaceutically acceptable salt thereof,

3. A compound of Formula (XV), or a pharmaceutically acceptable salt thereof,

8. (canceled)

18. A compound, or a pharmaceutically acceptable salt thereof, selected from the group consisting of: