Compounds and methods for modulating adenosine A2B receptor and adenosine A2A receptor

1. A compound having the formula:

wherein

L 1 is substituted or unsubstituted C 1 -C 3 alkylene;

Ring A is phenyl, pyridyl, pyrimidinyl, pyridazinyl, or pyrazinyl;

Ring B is heterocycloalkyl;

R 1 is independently halogen, —CX 1 3 , —CHX 1 2 , —CH 2 X 1 , —OCX 1 3 , —OCH 2 X 1 , —OCHX 1 2 , —CN, —SR 1D , —NR 1A R 1B , —C(O)R 1C , —C(O)OR 1C , —C(O)NR 1A R 1B , —OR 1D , —NR 1A C(O)R 1C , —NR 1A C(O)OR 1C , —SO 2 R 1D , —SO 2 NR 1A R 1B , —NR 1A SO 2 R 1D , substituted or unsubstituted alkyl, or substituted or unsubstituted heteroalkyl;

z1 is an integer from 0 to 5;

R 4 is hydrogen, —CX 4 3 , —NR 4A R 4B , or substituted or unsubstituted C 1 -C 6 alkyl;

R 5 is hydrogen or substituted or unsubstituted C 1 -C 6 alkyl;

R 6 is independently halogen, —CX 6 3 , —CHX 6 2 , —CH 2 X 6 , —OCX 6 3 , —OCH 2 X 6 , —OCHX 6 2 , —CN, —SR 6D , —SO 2 R 6D , —NR 6A R 6B , —C(O)R 6C , —C(O)OR 6C , —C(O)NR 6A R 6B , —C(O)NR 6A OR 6B , —OR 6D , —NR 6A C(O)R 6C , —NR 6A C(O)OR 6C , substituted or unsubstituted alkyl, or substituted or unsubstituted heteroalkyl;

z6 is an integer from 1 to 10;

each R 1A , R 1B , R 1C , R 1D , R 4A , R 4B , R 6A , R 6B , R 6C , and R 6D is independently hydrogen, halogen, —CF 3 , —CBr 3 , —CCl 3 , —CI 3 , —CHF 2 , —CHBr 2 , —CHCl 2 , —CHI 2 , —CH 2 F, —CH 2 Br, —CH 2 Cl, —CH 2 I, —OCF 3 , —OCBr 3 , —OCCl 3 , —OCI 3 , —OCHF 2 , —OCHBr 2 , —OCHCl 2 , —OCHI 2 , —OCH 2 F, —OCH 2 Br, —OCH 2 Cl, —OCH 2 I, —CN, —OH, —NH 2 , —COOH, —CONH 2 , —NO 2 , —SH, —SO 3 H, —SO 4 H, —SO 2 NH 2 , —NHNH 2 , —ONH 2 , —NHC(O)NHNH 2 , —NHC(O)NH 2 , —NHSO 2 H, —NHC(O)H, —NHC(O)OH, —NHOH, substituted or unsubstituted alkyl, substituted or unsubstituted heteroalkyl, substituted or unsubstituted cycloalkyl, substituted or unsubstituted heterocycloalkyl, substituted or unsubstituted aryl, or substituted or unsubstituted heteroaryl;

R 1A and R 1B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl;

R 4A and R 4B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl;

R 6A and R 6B substituents bonded to the same nitrogen atom may optionally be joined to form a substituted or unsubstituted heterocycloalkyl; and

each X 1 , X 4 , and X 6 is independently —F, —Cl, —Br, or —I.

2. The compound of claim 1 , wherein Ring B is pyrrolidinyl or piperidinyl.

3. The compound of claim 1 , wherein Ring A is pyridyl.

4. The compound of claim 1 , having the formula:

5. The compound of claim 1 , wherein L 1 is unsubstituted C 1 -C 3 alkylene.

6. The compound of claim 1 , wherein R 4 is hydrogen or unsubstituted methyl.

7. The compound of claim 1 , wherein R 5 is hydrogen or unsubstituted methyl.

8. The compound of claim 1 , wherein z6 is 1.

9. The compound of claim 1 , wherein R 6 is independently —NR 6A R 6B , —C(O)NR 6A R 6B , —C(O)NR 6A OR 6B , —OR 6D , —NR 6A C(O)R 6C , substituted or unsubstituted C 1 -C 6 alkyl, substituted or unsubstituted 2 to 6 membered heteroalkyl.

10. The compound of claim 1 , wherein R is independently —OH, —OCH 3 , —OCH 2 CH 3 , —CH 2 OH, or —CH 2 OCH 3 .

11. The compound of claim 1 , having the formula:

12. The compound of claim 1 , wherein R 1 is independently halogen, —CF 3 , —CN, —OH, —OCH 3 , —OCH 2 CH 3 , or —CH 3 .

13. The compound of claim 1 , wherein z1 is 0, 1, or 2.

14. The compound of claim 1 , wherein z6 is 2.

15. A pharmaceutical composition comprising the compound of claim 1 , and a pharmaceutically acceptable excipient.