Histone demethylase inhibitors

Patent metadata

Field	Value
Publication number	US-2017334879-A1
Application number	US-201715616319-A
Country	US
Kind code	A1
Filing date	Jun 7, 2017
Priority date	Mar 14, 2013
Publication date	Nov 23, 2017
Grant date	—

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.

First claim

We claim:

1 . A compound having the structure of Formula (II):

or a pharmaceutically acceptable salt thereof,
wherein:
R 1 is hydrogen, halogen, —OH, —N(R 5 ) 2 , alkyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, carbocyclylalkyl, heterocyclylalkyl, aralkyl, or heteroarylalkyl;
R 2 is alkyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, carbocyclylalkyl, heterocyclylalkyl, aralkyl, or heteroarylalkyl;
R 3 is hydrogen, halogen, —OH, —NH 2 , —NH(C1-C3alkyl) or C1-C3alkyl;
R 4 is —CO 2 H, —CO 2 R 6 , —C(O)N(H)CN, —C(O)N(H)OH, or tetrazolyl;
each R 5 is independently hydrogen, alkyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, carbocyclylalkyl, heterocyclylalkyl, aralkyl, or heteroarylalkyl; and
R 6 is alkyl.

2 . The compound of claim 1 , wherein R 3 is hydrogen.

3 . The compound of claim 1 , wherein R 4 is —CO 2 H.

4 . The compound of claim 1 , wherein R 4 is —CO 2 R 6 .

5 . The compound of claim 1 , wherein R 4 is —C(O)N(H)CN.

6 . The compound of claim 1 , wherein R 4 is tetrazolyl.

7 . The compound of claim 1 , wherein R 2 is alkyl.

8 . The compound of claim 1 , wherein R 2 is methyl.

9 . The compound of claim 1 , wherein R 2 is alkyl substituted with alkoxy.

10 . The compound of claim 1 , wherein R 2 is alkyl substituted with dialkylamino.

11 . The compound of claim 1 , wherein R 2 is alkyl substituted with (aryl)(alkyl)amino.

12 . The compound of claim 1 , wherein R 2 is alkyl substituted with (carbocyclyl)(alkyl)amino.

13 . The compound of claim 1 , wherein R 2 is alkyl substituted with (heteroaryl)(alkyl)amino.

14 . The compound of claim 1 , wherein R 2 is alkyl substituted with (heterocyclyl)(alkyl)amino.

15 . The compound of claim 1 , wherein R 2 is alkyl substituted with (aralkyl)(alkyl)amino.

16 . The compound of claim 1 , wherein R 2 is alkyl substituted with (carbocyclylalkyl)(alkyl)amino.

17 . The compound of claim 1 , wherein R 2 is alkyl substituted with (heteroarylalkyl)(alkyl)amino.

18 . The compound of claim 1 , wherein R 2 is alkyl substituted with (heterocyclylalkyl)(alkyl)amino.

19 . The compound of claim 1 , wherein R 2 is heterocyclyl.

20 . The compound of claim 1 , wherein R 2 is heterocyclylalkyl.

21 . The compound of claim 1 , wherein R 2 is heteroaryl.

22 . The compound of claim 1 , wherein R 2 is heteroarylalkyl.

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

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

25 . The compound of claim 24 , wherein R 1 is phenyl optionally substituted with one or more groups selected from halogen, —OH, —OR 5 , —N(R 5 ) 2 , —CON(R 5 ) 2 , alkyl, alkynyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, carbocyclylalkyl, heterocyclylalkyl, aralkyl, and heteroarylalkyl.

26 . The compound of claim 24 , wherein R 1 is phenyl optionally substituted with one or more groups selected from halogen, —OH, —OR 5 , 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.

Assignees

• Celgene Quanticel Res Inc

Inventors

• Kanouni Toufike
• Nie Zhe
• Stafford Jeffrey Alan
• Veal James Marvin

Classifications

• A61P35/00

  Antineoplastic agents · CPC title

• A61P43/00

  Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00 · CPC title

• A61K31/00

  Medicinal preparations containing organic active ingredients · CPC title

• A61K31/4709

  Non-condensed quinolines and containing further heterocyclic rings · CPC title

• C07D401/14

  containing three or more hetero rings · CPC title