Histone demethylase inhibitors
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.
1. A compound of Formula (I), or pharmaceutically acceptable salt thereof,
wherein, R is hydrogen or alkyl;
G is —X—Y;
X is unsubstituted —C1-C5 alkylene, unsubstituted —(C1-C5 alkylene)—Z—(C1-C5 alkylene)—, or unsubstituted —(C1-C5 alkylene)—Z—;
Y is unsubstituted carbocyclyl, unsubstituted heterocyclyl, unsubstituted aryl, or unsubstituted heteroaryl; and
and n is 0, 1, 2, or 3;
Z is unsubstituted
with the provision:
G is not
2. The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein X is a C1 alkylene.
3. The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein X is a C2 alkylene.
4. The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein X is a C3 alkylene.
5. The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein X is —(C1-C5 alkylene)—Z—.
6. The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein X is —(C1 alkylene)—Z—.
7. The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein X is —(C1 alkylene)—Z—, and n is 0, 1 or 2.
8. The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein Y is carbocyclyl.
9. The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein Y is heterocyclyl.
10. The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein Y is aryl.
11. The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein Y is heteroaryl.
12. The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein R is hydrogen.
13. The compound of claim 1 , or pharmaceutically acceptable salt thereof, wherein R is alkyl.
14. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound of Formula (I) as described in claim 1 , or pharmaceutically acceptable salt thereof.
15. A method of inhibiting a histone demethylase enzyme comprising contacting the histone demethylase enzyme with a compound of Formula (I) as described in claim 1 .
16. A method of treating cancer in a subject in need thereof comprising administering to the subject a composition comprising a compound of Formula (I) as described in claim 1 , or pharmaceutically acceptable salt thereof.