| 15566292 |
Peng H, Kumaravel G, Yao G, Sha L, Wang J, Van Vlijmen H, Bohnert T, Huang C, Vu CB, Ensinger CL, Chang H, Engber TM, Whalley ET, Petter RC: Novel bicyclic piperazine derivatives of triazolotriazine and triazolopyrimidines as highly potent and selective adenosine A2A receptor antagonists. J Med Chem. 2004 Dec 2;47(25):6218-29.
A series of bicyclic piperazine derivatives of triazolotriazine and triazolopyrimidines was synthesized. Some of these analogues show high affinity and excellent selectivity for adenosine A (2a) receptor versus the adenosine A (1) receptor. Structure-activity-relationship (SAR) studies based on octahydropyrrolo [1,2-a] pyrazine and octahydropyrido [1,2-a] pyrazine with various capping groups are reported. Among these analogues, the most potent and selective A (2a) antagonist 26 h has a K (i) value of 0.2 nM and is 16 500-fold selective with respect to the A (1) receptor. Among a number of compounds tested, compounds 21a and 21c exhibited significantly improved metabolic stability. Compounds 21a, 21c, and 18a showed good oral efficacy in rodent catalepsy models of Parkinson's disease. |
31(0,1,1,1) |