Histone demethylase inhibitors
Provided herein are substituted pyrazolylpyridine, pyrazolylpyridazine, and pyrazolylpyrimidine 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 (II), or a pharmaceutically acceptable salt thereof,
wherein,
R 1 is hydrogen, halogen, —OH, —OR 5 , —N(R 5 ) 2 , alkyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, carbocyclylalkyl, heterocyclylalkyl, aralkyl, or heteroarylalkyl;
R 2 is hydrogen, halogen, —OH, —OR 5 , —N(R 5 ) 2 , alkyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, carbocyclylalkyl, heterocyclylalkyl, aralkyl, or heteroarylalkyl;
R 4 is hydrogen or alkyl; and
each R 5 is independently hydrogen, alkyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, carbocyclylalkyl, heterocyclylalkyl, aralkyl, or heteroarylalkyl.
2. The compound or pharmaceutically acceptable salt of claim 1 , wherein R 4 is hydrogen.
3. The compound or pharmaceutically acceptable salt of claim 1 , wherein R 4 is alkyl.
4. The compound or pharmaceutically acceptable salt of claim 1 , wherein R 1 or R 2 is alkyl.
5. The compound or pharmaceutically acceptable salt of claim 1 , wherein R 1 or R 2 is carbocyclyl.
6. The compound or pharmaceutically acceptable salt of claim 1 , wherein R 1 or R 2 is aryl.
7. The compound or pharmaceutically acceptable salt of claim 1 , wherein R 1 or R 2 is aralkyl.
8. A compound of Formula (IV) or a pharmaceutically acceptable salt thereof,
wherein,
R 1 is hydrogen, halogen, —OH, —OR 5 , —N(R 5 ) 2 , alkyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, carbocyclylalkyl, heterocyclylalkyl, aralkyl, or heteroarylalkyl;
R 2 is hydrogen, halogen, —OH, —OR 5 , —N(R 5 ) 2 , alkyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, carbocyclylalkyl, heterocyclylalkyl, aralkyl, or heteroarylalkyl;
R 3 is —O—X—Y;
R 4 is hydrogen or alkyl;
each R 5 is independently hydrogen, alkyl, carbocyclyl, heterocyclyl, aryl, heteroaryl, carbocyclylalkyl, heterocyclylalkyl, aralkyl, or heteroarylalkyl;
X is C 1 -C 8 alkylene or
where n is 0 to 4; and
Y is hydrogen, carbocyclyl, aryl, or heteroaryl.
9. The compound or pharmaceutically acceptable salt of claim 8 , wherein R 4 is hydrogen.
10. The compound or pharmaceutically acceptable salt of claim 8 , wherein R 4 is alkyl.
11. The compound or pharmaceutically acceptable salt of claim 8 , wherein R 1 and R 2 are hydrogen.
12. The compound or pharmaceutically acceptable salt of claim 8 , wherein X is C-C 4 alkylene.
13. The compound or pharmaceutically acceptable salt of claim 8 , wherein X is C 1 -C 2 alkylene.
14. The compound or pharmaceutically acceptable salt of claim 8 , wherein X is C 1 alkylene.
15. The compound or pharmaceutically acceptable salt of claim 8 , wherein Y is hydrogen.
16. The compound or pharmaceutically acceptable salt of claim 8 , wherein Y is carbocyclyl.
17. The compound or pharmaceutically acceptable salt of claim 8 , wherein Y is aryl.
18. The compound or pharmaceutically acceptable salt of claim 8 , wherein Y is a phenyl.
19. The compound or pharmaceutically acceptable salt of claim 8 , wherein Y is heteroaryl.
20. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound Formula (II) or a pharmaceutically acceptable salt thereof.
21. A pharmaceutical composition comprising a pharmaceutically acceptable carrier and a compound Formula (IV) or a pharmaceutically acceptable salt thereof.