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 imizazo-fused heterocycle compounds useful to treat leukemia and other hematopoietic disorders.
1. A compound of Formula I:
or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof,
wherein
X is CR 4a ;
X′ is CR 4b ;
Y is N;
Y′ is CR 5b ;
R 1 is selected from the group consisting of hydrogen, halogen, —OR 6 , —CN, —NR 7 R 8 , —CH 2 OR 6 , —CH 2 NR 7 R 8 , an optionally substituted C 1-6 alkyl, an optionally substituted C 1-6 haloalkyl, an optionally substituted C 2-6 alkenyl, an optionally substituted C 2-6 alkynyl, an optionally substituted (5 to 7 membered heterocyclyl)alkyl, an optionally substituted 5 to 7 membered heterocyclyl, an optionally substituted aralkyl; an optionally substituted (5 or 6 membered heteroaryl)alkyl, 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 of R 2 , R 3 , R 4a and R 4b is independently selected from the group consisting of hydrogen, halogen, C 1-6 alkyl, OH, and C 1-6 alkoxy;
R 5b is selected from the group consisting of 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;
each R 6 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; 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 R 4a and R 4b 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 selected from piperidinyl-CH 2 — or morpholine-CH 2 —.
8. The compound of claim 1 , wherein R 1 is an optionally substituted 5 to 7 membered heterocyclyl.
9. The compound of claim 8 , wherein R 1 is an optionally substituted 6 membered heterocyclyl.
10. The compound of claim 9 , wherein R 1 is selected from optionally substituted morpholinyl, optionally substituted piperazinyl, or optionally substituted piperidinyl.
11. The compound of claim 1 , wherein R 2 is hydrogen.
12. The compound of claim 1 , wherein R 3 is hydrogen.
13. The compound of claim 1 , wherein R 5b is an optionally substituted 5 to 10 membered heteroaryl.
14. The compound of claim 13 , wherein R 5b is an optionally substituted 6 membered heteroaryl.
15. The compound of claim 14 , wherein R 5b is selected from pyridyl, pyrazinyl, pyridazinyl, or pyrimidyl.
16. The compound of claim 13 , wherein R 5b is an optionally substituted 5 membered heteroaryl.
17. The compound of claim 16 , wherein R 5b is pyrazolyl.
18. The compound claim 1 , selected from
pharmaceutically acceptable salts, esters, amides, or prodrugs thereof.
19. A pharmaceutical composition comprising an effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt, ester, amide, or prodrug thereof, and a pharmaceutically acceptable carrier, diluent, excipient or combinations thereof.