N-pyrazole A2A receptor agonists
View Patent ↗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 are disclosed.
1. A method for stimulating coronary vasodilatation in a mammal by administering to the mammal a therapeutically effective amount of a compound of Formula I
namely (1-{9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-aminopurin-2-yl}pyrazol-4-yl)-N-methylcarboxamide.
2. The method of claim 1 wherein the mammal is a human.
3. A pharmaceutical composition comprising the compound of Formula I
namely (1-{9-[(2R,3R,4S,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-aminopurin-2-yl}pyrazol-4-yl)-N-methylcarboxamide, and one or more pharmaceutical excipients.
4. The pharmaceutical composition of claim 3 wherein the pharmaceutical composition is in the form of a solution.
5. A method of producing coronary vasodilation without peripheral vasodilation comprising administering a compound of Formula I
namely (1-{9-[(2R,3R,4S ,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-aminopurin-2-yl}pyrazol-4-yl)-N-methylcarboxamide, to a human.
6. The method of claim 5 wherein the compound of Formula I is administered by iv bolus.
7. The method of claim 6 wherein the compound of Formula I is administered in from about 10 to about 30 seconds.
8. A method of myocardial perfusion imaging of a human, comprising administering a radionuclide and a compound of Formula I.
namely (1-{9-[(2R,3R,4S ,5R)-3,4-dihydroxy-5-(hydroxymethyl)oxolan-2-yl]-6-aminopurin-2-yl}pyrazol-4-yl)-N-methylcarboxamide, to the human wherein the myocardium is examined for areas of insufficient blood flow following administration of the radionuclide and the compound of Formula I.
9. The pharmaceutical composition of claim 3 wherein the pharmaceutical composition is formulated for injection.
10. The method of claim 1 , wherein the amount of the compound of Formula I is sufficient to stress the heart and induce a coronary steal situation.
11. The method of claim 1 , wherein the amount of the compound of Formula I administered is sufficient for imaging heart or coronary activity in the mammal.
12. The method of claim 1 wherein the compound of Formula I is administered by iv bolus.
13. The method of claim 12 wherein the compound of Formula I is administered in from about 10 to about 30 seconds.
14. The method of claim 5 , wherein the amount of the compound of Formula I is sufficient to stress the heart and induce a coronary steal situation.
15. The method of claim 5 , wherein the amount of the compound of Formula I administered is sufficient for imaging heart or coronary activity in the mammal.
16. The method of claim 5 wherein the therapeutically effective amount ranges from about 0.01 to about 100 mg/kg weight of the mammal.
17. The method of claim 8 , wherein the amount of the compound of Formula I is sufficient to stress the heart and induce a coronary steal situation.
18. The method of claim 8 , wherein the amount of the compound of Formula I administered is sufficient for imaging heart or coronary activity in the mammal.
19. The method of claim 8 wherein the compound of Formula I is administered by iv bolus.
20. The method of claim 19 wherein the compound of Formula I is administered in from about 10 to about 30 seconds.
21. The method of claim 8 wherein the therapeutically effective amount ranges from about 0.01 to about 100 mg/kg weight of the mammal.
22. The method of claim 1 wherein the therapeutically effective amount ranges from about 0.01 to about 100 mg/kg weight of the mammal.