Inhibitors of lysine specific demethylase-1
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.
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 .