2-heteroaryl-pyrazolo-[4,3-e]-1,2,4-triazolo-[1,5-c]-pyrimidine adenosine A2a receptor antagonists

1. A compound having the structural formula

or a pharmaceutically acceptable salt thereof, wherein

R is R 1 -isoxazolyl, R 1 -oxadiazolyl, R 1 -dihydrofuranyl, R 1 -pyrazolyl, R 1 -imidazolyl, R 1 -pyrazinyl or R 1 -pyrimidinyl;

R 1 is 1, 2 or 3 substituents independently selected from the group consisting of H, alkyl, alkoxy and halo;

Z is R 2 -aryl or R 2 -heteroaryl;

R 2 is 1 to 5 substituents independently selected from the group consisting of hydrogen, alkyl, hydroxyalkyl, -alkylene-O—C(O)alkyl, alkoxyalkyl, (hydroxy)haloalkyl, (cycloalkyl)hydroxyalkyl, hydroxycycloalkyl, (halo)alkoxyalkyl, —C(O)alkyl, hydroxyalkoxy, alkoxyalkoxy, oxetanyloxy, halo, cyanoalkyl, haloalkyl, dialkylamino, R 3 -heteroaryl and R 3 -heteroarylalkyl; and

R 3 is 1 to 3 substituents independently selected from the group consisting of H, alkyl, alkoxyalkyl, hydroxyalkyl, dialkylamino and cycloalkylaminocarbonyl.

2. A compound of claim 1 wherein R is R 1 -pyrazinyl or R 1 -dihydrofuranyl.

3. A compound of claim 2 wherein R 1 is one substituent selected from the group consisting of H and alkyl.

4. A compound of claim 1 wherein Z is R 2 -phenyl and R 2 is 1 to 3 substituents independently selected from the group consisting of halo, alkoxyalkyl or R 3 -heteroaryl.

5. A compound of claim 4 wherein R 2 is two substituents, and one substituent is 2-fluoro and the other is halo, alkoxyalkyl, or R 3 -heteroaryl.

6. A compound of claim 5 wherein the heteroaryl group in R 3 -heteroaryl is oxazolyl, 1,2,4-oxadiazolyl, isoxazolyl or thiazolyl, and the R 3 substituent is 1 or 2 groups independently selected from H, alkyl and alkoxyalkyl.

7. A compound of claim 1 wherein Z is R 2 -benzoxazolyl, R 2 -benzisoxazolyl or R 2 -indazolyl and R 2 is 1 to 3 substituents independently selected from the group consisting of H, halo and alkyl.

8. A compound of claim 7 wherein Z is R 2 -benzoxazolyl or R 2 -benzisoxazolyl, and R 2 is two substituents, wherein one substituent is a fluoro group adjacent to the attachment point of Z and the other is H or an alkyl group on the oxazolyl or isoxazolyl portion of Z.

9. A compound of claim 7 wherein Z is R 2 -indazolyl, and R 2 is three substituents, wherein one substituent is a fluoro group adjacent to the attachment point of Z and the other two are alkyl groups on the indazolyl portion of Z.

10. A compound of claim 1 selected from the group consisting of

or a pharmaceutically acceptable salt thereof.

11. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 in a pharmaceutically acceptable carrier.

12. A method of treating central nervous system diseases comprising administering an effective amount of a compound of claim 1 to a mammal in need of such treatment.

13. The method of claim 12 for treating Parkinson's disease, Extra Pyramidal Syndrome, restless legs syndrome, essential tremor, Huntington's Disease, attention deficit hyperactivity disorder, cognitive impairment, negative symptoms of schizophrenia, depression, stroke or psychoses.

14. The method of claim 13 for treating Parkinson's disease, Extra Pyramidal Syndrome, restless legs syndrome or attention deficit hyperactivity disorder.

15. A pharmaceutical composition comprising a therapeutically effective amount of a combination of a compound of claim 1 , and 1 to 3 other agents useful in treating Parkinson's disease in a pharmaceutically acceptable carrier.

16. A method of treating Parkinson's disease comprising administering to a mammal in need of such treatment an effective amount of a combination of a compound of claim 1 , and 1 to 3 other agents useful in treating Parkinson's disease.

17. The method of claim 16 wherein the other agents are selected from the group consisting of L-DOPA, dopaminergic agonists, MAO-B inhibitors, DOPA decarboxylase inhibitors and COMT inhibitors.