This specification discloses 2-adenosine N-pyrazole compounds having the following formula: and methods for using the compounds as A2A receptor agonists to stimulate mammalian coronary vasodilatation for therapeutic purposes and for purposes of imaging the heart.
1. A compound having the formula:
wherein R 1 =CH 2 OH;
R 2 and R 4 are each hydrogen;
R 3 is —CONR 7 R 8
R 7 is selected from the group consisting of hydrogen and C 1-3 alkyl; and
R 8 is selected from the group consisting of hydrogen and C 1-8 alkyl.
2. The compound of claim 1 wherein R 7 is hydrogen and R 8 is C 1-8 alkyl.
3. The compound of claim 1 wherein R 7 is C 1-3 alkyl and R 8 is hydrogen.
4. The compound of claim 1 wherein R 7 is C 1-3 alkyl and R 8 is C 1-8 alkyl.
5. The compound of claim 1 wherein R 7 is hydrogen and R 8 is hydrogen.
6. The compound of claim 1 wherein R 7 is selected from the group consisting of hydrogen and C 1-2 alkyl.
7. The compound of claim 1 wherein R 7 is hydrogen.
8. The compound of claim 1 wherein R 8 is hydrogen.
9. The compound of claim 1 wherein R 8 is methyl.
10. A method for stimulating coronary vasodilation in a mammal by administering to the mammal in need thereof a therapeutically effective amount of the compound of claim 1 .
11. The method of claim 10 wherein the mammal is a human.
12. The method of claim 10 , wherein the therapeutically effective amount of the compound is sufficient to stress the heart and induce a coronary steal situation.
13. The method of claim 10 , wherein the therapeutically effective amount of the compound is sufficient for imaging heart or coronary activity in the mammal.
14. The method of claim 10 wherein the compound is administered by iv bolus.
15. The method of claim 14 wherein the compound is administered in from 10 to 30 seconds.
16. A method of producing coronary vasodilation without peripheral vasodilation comprising administering a compound of claim 1 to a human in need thereof.
17. The method of claim 16 wherein the compound is administered by iv bolus.
18. The method of claim 16 wherein the compound is administered in from 10 to about seconds.
19. The method of claim 16 , wherein the compound is administered in an amount that is sufficient for imaging heart or coronary activity.
20. A method of myocardial perfusion imaging of a human, comprising administering a radionuclide and a compound of claim 1 to the human in need thereof wherein the myocardium is examined for areas of insufficient blood flow following administration of the radionuclide and the compound.
21. The method of claim 20 , wherein the amount of the compound is sufficient to stress the heart and induce a coronary steal situation.
22. The method of claim 20 wherein the compound is administered by iv bolus.
23. The method of claim 22 wherein the compound is administered in from 10 to 30 seconds.
24. The method of claim 20 wherein the compound is administered before the radionucleotide is administered.
25. A pharmaceutical composition comprising a compound of claim 1 and at least one pharmaceutical excipient.
26. The pharmaceutical composition of claim 25 wherein the pharmaceutical composition is in the form of a solution.
27. The pharmaceutical composition of claim 25 wherein the pharmaceutical composition is formulated for injection.