Inhibitors of lysine specific demethylase-1

Patent metadata

Field	Value
Publication number	US-9771329-B2
Application number	US-201615018814-A
Country	US
Kind code	B2
Filing date	Feb 8, 2016
Priority date	May 1, 2014
Publication date	Sep 26, 2017
Grant date	Sep 26, 2017

Abstract

The present invention relates generally to compositions and methods for treating cancer and neoplastic disease. Provided herein are substituted heterocyclic derivative compounds and pharmaceutical compositions comprising said compounds. The subject compounds and compositions are useful for inhibition of lysine specific demethylase-1. Furthermore, the subject compounds and compositions are useful for the treatment of cancer.

First claim

We claim:

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

wherein,
W is N, C—H, or C—F;
X is hydrogen, halogen, CN, optionally substituted alkynyl, optionally substituted carbocyclylalkynyl, optionally substituted aryl, or optionally substituted heteroaryl;
Y is hydrogen, optionally substituted alkyl, optionally substituted cycloalkyl, or optionally substituted cycloalkylalkyl; and
Z is an optionally substituted group chosen from N-attached heterocyclyl, —O-heterocyclylalkyl, —N(H)-heterocyclyl, —N(Me)-heterocyclyl, —N(H)-heterocyclylalkyl, or —N(Me)-heterocyclylalkyl.

2. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein W is C—H.

3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein W is C—F.

4. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein X is selected from the group consisting of hydrogen, halogen, optionally substituted carbocyclylalkynyl, optionally substituted aryl, and optionally substituted heteroaryl.

5. The compound of claim 4 , or a pharmaceutically acceptable salt thereof, wherein X is optionally substituted aryl.

6. The compound of claim 5 , or a pharmaceutically acceptable salt thereof, wherein the optionally substituted aryl is an optionally substituted phenyl.

7. The compound of claim 4 , or a pharmaceutically acceptable salt thereof, wherein X is an optionally substituted heteroaryl.

8. The compound of claim 7 , or a pharmaceutically acceptable salt thereof, wherein X is selected from the group consisting of optionally substituted pyridinyl, optionally substituted pyrazolyl, and optionally substituted indazolyl.

9. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Z is selected from the group consisting of optionally substituted —N(H)-heterocyclylalkyl, optionally substituted N-attached heterocyclyl, and optionally substituted —N(Me)-heterocyclylalkyl.

10. The compound of claim 9 , or a pharmaceutically acceptable salt thereof, wherein the alkyl of said —N(H)-heterocyclylalkyl or —N(Me)-heterocyclylalkyl group is C 1 -C 3 alkyl.

11. The compound of claim 9 , or a pharmaceutically acceptable salt thereof, wherein said heterocyclyl is an optionally substituted nitrogen-containing 4-, 5-, 6-, or 7-membered heterocyclyl.

12. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Z is an optionally substituted N-attached heterocyclyl.

13. The compound of claim 12 , or a pharmaceutically acceptable salt thereof, wherein said optionally substituted N-attached heterocyclyl is 4-, 5-, 6-, or 7-membered N-attached heterocyclyl.

14. The compound of claim 13 , or a pharmaceutically acceptable salt thereof, wherein said optionally substituted N-attached heterocyclyl is 6-membered N-attached heterocyclyl.

15. The compound of claim 12 , or a pharmaceutically acceptable salt thereof, wherein said optionally substituted N-attached heterocyclyl is an optionally substituted piperidine.

16. The compound of claim 15 , or a pharmaceutically acceptable salt thereof, wherein the optionally substituted piperidine is 4-aminopiperidine.

17. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein Y is optionally substituted C 1 -C 3 alkyl or methyl.

18. A pharmaceutical composition comprising the compound of claim 1 and at least one pharmaceutically acceptable excipient.

19. A method of treating acute myeloid leukemia, breast cancer, or prostate cancer in a patient in need thereof, comprising administering to the patient the pharmaceutical composition of claim 18 .

Assignees

• Celgene Quanticel Res Inc

Inventors

• Chen Young K
• Kanouni Toufike
• Kaldor Stephen W
• Stafford Jeffrey Alan
• Veal James Marvin

Classifications

• A61P43/00

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

• A61P35/02

  specific for leukemia · CPC title

• A61P35/00

  Antineoplastic agents · CPC title

• C07D471/10

  Spiro-condensed systems · CPC title

• C07D401/04 Primary

  directly linked by a ring-member-to-ring-member bond · CPC title