IP Library › Granted Patent US 9,242,968
Granted Patent B2
US 9,242,968 · App. 14/751,007 · Granted Jan 26, 2016

Histone demethylase inhibitors

Inventors: Amogh Boloor (San Diego, CA); Young K. Chen (San Marcos, CA); Michael Brennan Wallace (San Diego, CA)
Assignee: QUANTICEL PHARMACEUTICALS, INC.
C07D409/14C07D213/79C07D401/12C07D405/12C07D405/14
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Quick Facts
Patent No.
US 9,242,968
App. No.
14/751,007
Granted
Jan 26, 2016
Kind
B2
Abstract

The present disclosure relates generally to compositions and methods for treating cancer and neoplastic disease. Provided herein are substituted pyridine 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 (36)

1. A compound, or a stereoisomer or pharmaceutically acceptable salt thereof, having the structure of Formula (II):

wherein, X is O;

R 6 is chosen from optionally substituted heterocyclyl, optionally substituted heterocyclyloxy, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkoxy, optionally substituted C 6 -C 10 aryl-SO 2 —, optionally substituted heteroaryl-S—, or —N(R 1 )(R 2 ), wherein R 1 is hydrogen or optionally substituted alkyl, and R 2 is chosen from optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl-CO—, optionally substituted heteroaryl-CO—, optionally substituted cycloalkyl-CO—, or optionally substituted alkyl-CO—; and

each R 5 , R 7 and R 8 is independently chosen from hydrogen, halogen, —OH, —CN, optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 alkoxy, optionally substituted C 3 -C 7 carbocyclyl, optionally substituted C 3 -C 7 carbocyclyloxy, optionally substituted C 4 -C 12 carbocyclylalkyl, optionally substituted C 4 -C 12 carbocyclylalkoxy, optionally substituted C 1 -C 6 alkynyl, optionally substituted C 1 -C 6 alkenyl, optionally substituted C 6 -C 10 aryl, optionally substituted C 6 -C 10 aryloxy, optionally substituted C 6 -C 10 aryl-S—, optionally substituted C 7 -C 14 aralkoxy, optionally substituted heteroaryl, and optionally substituted heteroaryloxy, optionally substituted heterocyclyl, optionally substituted heterocyclyloxy, substituted heterocyclylalkyl, optionally substituted heterocyclylalkoxy, optionally substituted C 6 -C 10 aryl-SO 2 —, optionally substituted heteroaryl-S—, or —N(R 1 )(R 2 ), wherein R 1 is hydrogen or optionally substituted alkyl, and R 2 is chosen from optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl-CO—, optionally substituted heteroaryl-CO—, optionally substituted cycloalkyl-CO—, or optionally substituted alkyl-CO—;

with the provision that at least one of R 5 , R 7 and R 8 is hydrogen.

2. The compound, or pharmaceutically acceptable salt thereof, of claim 1 having the structure of Formula (IIa):

wherein, X is O;

R 6 is chosen from optionally substituted heterocyclyl, optionally substituted heterocyclyloxy, optionally substituted heterocyclylalkyl, optionally substituted heterocyclylalkoxy, optionally substituted C 6 -C 10 aryl-SO 2 —, optionally substituted heteroaryl-S—, or —N(R 1 )(R 2 ), wherein R 1 is hydrogen or optionally substituted alkyl, and R 2 is chosen from optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl-CO—, optionally substituted heteroaryl-CO—, optionally substituted cycloalkyl-CO—, or optionally substituted alkyl-CO—; and

each R 5 , R 7 and R 8 is independently chosen from hydrogen, halogen, —OH, —CN, optionally substituted C 1 -C 6 alkyl, optionally substituted C 1 -C 6 alkoxy, optionally substituted C 3 -C 7 carbocyclyl, optionally substituted C 3 -C 7 carbocyclyloxy, optionally substituted C 4 -C 12 carbocyclylalkyl, optionally substituted C 4 -C 12 carbocyclylalkoxy, optionally substituted C 1 -C 6 alkynyl, optionally substituted C 1 -C 6 alkenyl, optionally substituted C 6 -C 10 aryl, optionally substituted C 6 -C 10 aryloxy, optionally substituted C 6 -C 10 aryl-S—, optionally substituted C 7 -C 14 aralkoxy, optionally substituted heteroaryl, and optionally substituted heteroaryloxy, optionally substituted heterocyclyl, optionally substituted heterocyclyloxy, substituted heterocyclylalkyl, optionally substituted heterocyclylalkoxy, optionally substituted C 6 -C 10 aryl-SO 2 —, optionally substituted heteroaryl-S—, or —N(R 1 )(R 2 ), wherein R 1 is hydrogen or optionally substituted alkyl, and R 2 is chosen from optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl-CO—, optionally substituted heteroaryl-CO—, optionally substituted cycloalkyl-CO—, or optionally substituted alkyl-CO—;

with the provision that at least one of R 5 , R 7 and R 8 is hydrogen.

3. The compound, or pharmaceutically acceptable salt thereof, of claim 2 , wherein R 5 is hydrogen.

4. The compound, or pharmaceutically acceptable salt thereof, of claim 2 , wherein R 7 is hydrogen.

5. The compound, or pharmaceutically acceptable salt thereof, of claim 2 , wherein R 8 is hydrogen.

6. The compound, or pharmaceutically acceptable salt thereof, of claim 2 , wherein R 5 , R 7 and R 8 are hydrogen.

7. The compound, or pharmaceutically acceptable salt thereof, of claim 2 , wherein R 6 is optionally substituted heterocyclyl, or optionally substituted heterocyclyloxy.

8. The compound, or pharmaceutically acceptable salt thereof, of claim 2 , wherein R 6 is optionally substituted C 6 -C 10 aryl-SO 2 —, or optionally substituted heteroaryl-S—.

9. The compound, or pharmaceutically acceptable salt thereof, of claim 2 , wherein R 6 is —N(R 1 )(R 2 ), wherein R 1 is hydrogen; and R 2 is chosen from optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl-CO—, optionally substituted heteroaryl-CO—, optionally substituted cycloalkyl-CO—, or optionally substituted alkyl-CO—.

10. The compound, or pharmaceutically acceptable salt thereof, of claim 2 , wherein R 6 is —N(R 1 )(R 2 ), wherein R 1 is optionally substituted alkyl; and R 2 is chosen from optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl-CO—, optionally substituted heteroaryl-CO—, optionally substituted cycloalkyl-CO—, or optionally substituted alkyl-CO—.

11. The compound, or pharmaceutically acceptable salt thereof, of claim 6 , wherein R 6 is —N(R 1 )(R 2 ), wherein R 1 is optionally substituted alkyl; and R 2 is chosen from optionally substituted alkyl, optionally substituted aryl, optionally substituted heteroaryl, optionally substituted heterocyclyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl-CO—, optionally substituted heteroaryl-CO—, optionally substituted cycloalkyl-CO—, or optionally substituted alkyl-CO—.

12. The compound, or pharmaceutically acceptable salt thereof, of claim 11 , wherein R 2 is optionally substituted aryl.

13. The compound, or pharmaceutically acceptable salt thereof, of claim 11 , wherein R 2 is optionally substituted heteroaryl.

14. The compound, or pharmaceutically acceptable salt thereof, of claim 11 , wherein R 2 is optionally substituted heterocyclyl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted aryl-CO—, optionally substituted cycloalkyl-CO—, or optionally substituted alkyl-CO—.

15. The compound, or pharmaceutically acceptable salt thereof, of claim 12 , wherein R 1 is an optionally substituted C1-C3 alkyl.

16. The compound, or pharmaceutically acceptable salt thereof, of claim 12 , wherein R 1 is CH 3 group.

17. The compound, or pharmaceutically acceptable salt thereof, of claim 12 , wherein the optionally substituted aryl is substituted with at least one substituent selected from optionally substituted C1-C5 alkyl, optionally substituted C2-C5 alkenyl, halogen, cyano, hydroxy, amino, optionally substituted C1-C5 alkoxy, optionally substituted alkylamino, optionally substituted dialkylamino, optionally substituted heterocyclyl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkylalkoxy, or optionally substituted cycloalkoxy.

18. The compound, or pharmaceutically acceptable salt thereof, of claim 12 , wherein the optionally substituted aryl is substituted with at least one substituent selected from optionally substituted C1-C5 alkyl, halogen, optionally substituted C1-C5 alkoxy, optionally substituted heterocyclyl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkylalkoxy, or optionally substituted cycloalkoxy.

19. The compound, or pharmaceutically acceptable salt thereof, of claim 12 , wherein the optionally substituted aryl is substituted with at least one substituent selected from optionally substituted heterocyclyl, optionally substituted heteroaryl, optionally substituted cycloalkyl, optionally substituted cycloalkylalkyl, optionally substituted cycloalkylalkoxy, or optionally substituted cycloalkoxy.

20. The compound, or pharmaceutically acceptable salt thereof, of claim 12 , wherein the optionally substituted aryl is substituted with at least one substituent selected from optionally substituted C1-C5 alkyl, halogen, or optionally substituted C1-C5 alkoxy.

21. The compound, or pharmaceutically acceptable salt thereof, of claim 12 , wherein the optionally substituted aryl is substituted with at least one optionally substituted C1-C5 alkyl.

22. The compound, or pharmaceutically acceptable salt thereof, of claim 20 , wherein R 1 is a CH 3 group, and X is O.

23. The compound, or pharmaceutically acceptable salt thereof, of claim 2 , having the structure:

24. The compound, or pharmaceutically acceptable salt thereof, of claim 2 , having the structure:

25. The compound, or pharmaceutically acceptable salt thereof, of claim 2 , having the structure:

26. The compound, or pharmaceutically acceptable salt thereof, of claim 2 , having the structure:

27. The compound, or pharmaceutically acceptable salt thereof, of claim 2 , having the structure:

28. A pharmaceutical composition comprising a compound of Formula (II) as described in claim 1 , or pharmaceutically acceptable salt thereof, and pharmaceutically acceptable excipient.

Assignments (2)
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Apr 8, 2016
From: QUANTICEL PHARMACEUTICALS, INC.
To: CELGENE QUANTICEL RESEARCH, INC.
Reel/Frame 038399/0685 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jul 13, 2015
From: BOLOOR, AMOGH; CHEN, YOUNG K.; WALLACE, MICHAEL BRENNAN
To: QUANTICEL PHARMACEUTICALS, INC.
Reel/Frame 036073/0534 →
Continuity (2)
Provisional Application 62017201 · Jun 25, 2014
Related Publication 20150376169A1 · Dec 31, 2015