Heterocyclic compounds as adenosine antagonists
5,6-disubstituted 2-aminopyrazine compounds as modulators of an adenosine receptor are provided. The compounds may find use as therapeutic agents for the treatment of diseases mediated through a G-protein-coupled receptor signaling pathway and may find particular use in oncology.
1. A compound of the formula (III):
or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein:
A is
and
B is a phenyl substituted with 1 to 3 groups which may be the same or different, wherein at least one group is —CN, and wherein each group is halogen, —CF 3 , —OH, —OCH 3 , —CN, —C(O)OCH 3 , —C(O)OC 2 H 5 , —NH 2 , —NHCH 3 or C 1 -C 6 alkyl optionally substituted by halogen, —OH or oxo.
2. The compound of claim 1 , or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, wherein B is selected from the group consisting of
3. The compound of claim 1 , or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of
4. A pharmaceutical composition comprising a compound of claim 1 , or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, and a pharmaceutically acceptable carrier.
5. A method of inhibiting an adenosine receptor of subtype A 2A , A 2B or A 3 in a cell, comprising administering a compound of claim 1 , or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing, to the cell.
6. The method of claim 5 , wherein the adenosine receptor is of subtype A 2A .
7. A kit comprising a compound of claim 1 , or a tautomer or stereoisomer thereof, or a pharmaceutically acceptable salt of any of the foregoing.
8. The compound of claim 3 , or a pharmaceutically acceptable salt thereof, wherein the compound is
9. The compound of claim 3 , or a pharmaceutically acceptable salt thereof, wherein the compound is
10. The compound of claim 3 , or a pharmaceutically acceptable salt thereof, wherein the compound is
11. The compound of claim 3 , or a pharmaceutically acceptable salt thereof, wherein the compound is
12. The compound of claim 3 , or a pharmaceutically acceptable salt thereof, wherein the compound is
13. The compound of claim 3 , or a pharmaceutically acceptable salt thereof, wherein the compound is
14. The compound of claim 3 , or a pharmaceutically acceptable salt thereof, wherein the compound is
15. The compound of claim 3 , or a pharmaceutically acceptable salt thereof, wherein the compound is
16. The compound of claim 3 , or a pharmaceutically acceptable salt thereof, wherein the compound is
17. The compound of claim 3 , or a pharmaceutically acceptable salt thereof, wherein the compound is
18. The compound of claim 3 , or a pharmaceutically acceptable salt thereof, wherein the compound is
19. The compound of claim 3 , or a pharmaceutically acceptable salt thereof, wherein the compound is
20. The compound of claim 3 , or a pharmaceutically acceptable salt thereof, wherein the compound is