A class of novel antagonists for the adenosine A 3 receptor are disclosed. These compounds are useful as therapeutic agents for a number of diseases and medical conditions that are mediated by the A 3 receptor. The compounds of this invention are also useful as diagnostic agents for the A 3 receptor.
1. A compound of Formula (I):
wherein
X is CH or N;
R 1 and R 2 are each independently alkyl, substituted alkyl, aralkyl, substituted aralkyl, alkenyl, substituted alkenyl, alkynyl, substituted alkynyl, aryl, or substituted aryl, providing R 1 and R 2 are not both methyl;
R 3 is aryl, substituted aryl, alkyl, substituted alkyl, aralkyl, or substituted aralkyl, providing R 3 is not aryl or substituted aryl when X is CH and R 1 and R 2 are both n-propyl;
R 4 is hydrogen, alkyl, substituted alkyl, aralkyl, substituted aralkyl, aryl, or substituted aryl; and
one of the dashed lines represents a double bond and the other represents a single bond;
or a pharmaceutically acceptable salt thereof.
2. A compound according to claim 1 having Formula (Ia):
wherein R 1 , R 2 , R 3 and R 4 are as defined in claim 1 .
3. A compound according to claim 2 , wherein R 4 is hydrogen, alkyl, or substituted alkyl.
4. A compound according to claim 2 , wherein R 3 is alkyl, substituted alkyl, aryl, substituted aryl, or aralkyl.
5. A compound according to claim 2 , wherein R 1 and R 2 are each independently alkyl, substituted alkyl, or aralkyl.
6. A compound according to claim 1 having Formula (Ib):
wherein R 1 , R 2 , R 3 and R 4 are as defined in claim 1 .
7. A compound according to claim 6 , wherein R 4 is hydrogen, alkyl, or substituted alkyl.
8. A compound according to claim 6 , wherein R 3 is alkyl, substituted alkyl, aryl, substituted aryl, or aralkyl, providing R 3 is not aryl or substituted aryl when R 1 and R 2 are both n-propyl.
9. A compound according to claim 6 , wherein R 1 and R 2 are each independently alkyl, substituted alkyl, or aralkyl, providing R 1 and R 2 are not both methyl.
10. A compound according to claim 1 which is selected from the group consisting of:
1-Benzyl-7-phenyl-3-propyl-1H-pyrrolo[1,2-f]purine-2,4(3H,6H)-dione;
1-Benzyl-7-phenyl-3-propyl-1H-imidazo[1,2-f]purine-2,4(3H,8H)-dione;
1-Benzyl-7-(4-methoxyphenyl)-3-propyl-1H-imidazo[1,2-f]purine-2,4(3H,8H)-dione;
1-Benzyl-7-(biphenyl-4-yl)-3-propyl-1H-imidazo[1,2-f]purine-2,4(3H,8H)-dione;
1-Benzyl-7-(4-fluorophenyl)-3-propyl-1H-imidazo[1,2-f]purine-2,4(3H,8H)-dione;
7-Phenyl-1,3-dipropyl-1H-imidazo[1,2-f]purine-2,4(3H,8H)-dione;
1,3-Diisobutyl-7-phenyl-1H-imidazo[1,2-f]purine-2,4(3H,8H)-dione;
1-Benzyl-7-methyl-3-propyl-1H-imidazo[1,2-f]purine-2,4(3H,8H)-dione;
1-Benzyl-7-methyl-3-propyl-1H-pyrrolo[1,2-f]purine-2,4(3H,6H)-dione;
1-Benzyl-7-ethyl-3-propyl-1H-pyrrolo[1,2-f]purine-2,4(3H,6H)-dione;
1-Benzyl-6,7-dimethyl-3-propyl-1H-pyrrolo[1,2-f]purine-2,4(3H,6H)-dione;
1-Benzyl-7-ethyl-3-propyl-1H-imidazo[1,2-f]purine-2,4(3H,8H)-dione;
1-Benzyl-7-isopropyl-3-propyl-1H-imidazo[1,2-f]purine-2,4(3H,8H)-dione;
1-Benzyl-7-tert-butyl-3-propyl-1H-imidazo[1,2-f]purine-2,4(3H,8H)-dione;
1-Benzyl-7-cyclopropyl-3-propyl-1H-imidazo[1,2-f]purine-2,4(3H,8H)-dione;
1-Benzyl-7-cyclohexyl-3-propyl-1H-imidazo[1,2-f]purine-2,4(3H,8H)-dione;
1-Benzyl-6,7-dimethyl-3-propyl-1H-imidazo[1,2-f]purine-2,4(3H,8H)-dione; and
1-Benzyl-7-ethyl-6-methyl-3-propyl-1H-imidazo[1,2-f]purine-2,4(3H,8H)-dione;
or a pharmaceutically acceptable salt thereof.
11. A compound according to claim 1 which is 1-benzyl-7-methyl-3-propyl-1H-imidazo[1,2-f]purine-2,4(3H,8H)-dione; or a pharmaceutically acceptable salt thereof.
12. A method of treating a medical condition is selected from the group consisting of cerebral ischemia, inflammation, and asthma, which method comprises administering to a mammal a therapeutically effective amount of a compound of claim 1 .
13. A pharmaceutical composition comprising a compound of claim 1 and a pharmaceutically acceptable carrier.
14. A pharmaceutical composition according to claim 13 for the treatment of cerebral ischemia, inflammation and asthma.
15. A compound having the formula
or a pharmaceutically acceptable salt thereof.
16. A method of treating a medical condition selected from the group consisting of cerebral ischemia, inflammation and asthma, which method comprises administering to a mammal a therepeutically effective amount of a compound of claim 15 .
17. A pharmaceutical composition comprising a compound of claim 15 and a pharmaceutically acceptable carrier.
18. A pharmaceutical composition according to claim 17 for the treatment of cerebral ischemia, inflammation and asthma.