Imidazo-fused heterocycles and uses thereof
Compounds and methods in the fields of chemistry and medicine are disclosed. Some of the disclosed embodiments include compounds, compositions and methods of using imidazole-fused heterocycle amines. Some of the disclosed embodiments include imidazo-fused heterocycle compounds useful to treat leukemia and other hematopoietic disorders.
1. A compound of Formula (III):
or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof,
wherein
R 1 is selected from the group consisting of an optionally substituted (5 to 7 membered heterocyclyl)alkyl, an optionally substituted aralkyl; and an optionally substituted (5 or 6 membered heteroaryl)alkyl;
each of R 2 , R 3 , and R 4a is independently selected from the group consisting of hydrogen, halogen, C 1-6 alkyl, OH, and C 1-6 alkoxy;
each of R 5a and R 5b is independently selected from the group consisting of hydrogen, halogen, —OR 6 , —CN, —NR 7 R 8 , —CH 2 OR 6 , an optionally substituted aryl, an optionally substituted 5 to 10 membered heteroaryl, an optionally substituted 5-10 membered heterocyclyl, an optionally substituted C 3-7 carbocyclyl, an optionally substituted C 1-6 alkyl, an optionally substituted C 1-6 haloalkyl, an optionally substituted C 1-6 heteroalkyl, —C(═O)R 6 , —C(═O)OR 6 , —C(═O)NR 7 R 8 , —NHC(═O)R 6 , —SO 2 R 6 , and —SO 2 NR 7 R 8 ;
each R 6 is independently hydrogen, an optionally substituted C 1-10 alkyl, an optionally substituted C 1-10 haloalkyl, or an optionally substituted C 1-6 heteroalkyl; and
each R 7 and R 8 is independently selected from hydrogen; an optionally substituted C 1-10 alkyl; an optionally substituted C 1-10 haloalkyl; or an optionally substituted C 1-6 heteroalkyl; or R 7 and R 8 are joined together with the nitrogen atom to which they are attached to form an optionally substituted C 3-7 cycloalkyl or 3 to 7 membered heterocyclyl ring.
2. The compound of claim 1 , wherein each of R 4a and R 5a is hydrogen.
3. The compound of claim 1 , wherein R 1 is an optionally substituted (5 to 7 membered heterocyclyl)alkyl.
4. The compound of claim 3 , wherein R 1 is an optionally substituted (5 membered heterocyclyl)alkyl.
5. The compound of claim 4 , wherein R 1 is pyrrolidyl-CH 2 —.
6. The compound of claim 3 , wherein R 1 is an optionally substituted (6 membered heterocyclyl)alkyl.
7. The compound of claim 6 , wherein R 1 is piperidinyl-CH 2 — or morpholine-CH 2 —.
8. The compound of claim 1 , wherein R 2 is hydrogen.
9. The compound of claim 1 , wherein R 3 is hydrogen.
10. The compound of claim 1 , wherein R 5b is an optionally substituted 5 to 10 membered heteroaryl.
11. The compound of claim 10 , wherein R 5b is an optionally substituted 6 membered heteroaryl.
12. The compound of claim 11 , wherein R 5b is pyridyl, pyrazinyl, pyridazinyl, or pyrimidyl.
13. The compound of claim 10 , wherein R 5b is an optionally substituted 5 membered heteroaryl.
14. The compound of claim 13 , wherein R 5b is pyrazolyl.
15. The compound claim 1 , having the structure
or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof.
16. A pharmaceutical composition comprising an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof, and one or more pharmaceutically acceptable carriers, diluents, excipients, or combinations thereof.
17. The compound of claim 2 , wherein R 1 is an optionally substituted (5 to 7 membered heterocyclyl)alkyl.
18. The compound of claim 17 , wherein R 1 is an optionally substituted (5 membered heterocyclyl)alkyl.
19. The compound of claim 18 , wherein R 1 is pyrrolidyl-CH 2 —.