Potent, selective, and orally active adenosine A2A receptor antagonists:: Arylpiperazine derivatives of pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidines

Antagonism of the adenosine A(2A) receptor offers great promise in the treatment of Parkinson's disease. Employing the known pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine A(2A) antagonist SCH 58261 as a starting point, we identified the Potent and selective (vs. A1) antagonist 11 h, orally active in the rat haloperidol-induced catalepsy model. We further optimized this lead to the methoxyethoxyethyl ether 12a (SCH 420814), which shows broad selectivity, good pharmacokinetic properties, and excellent in vivo activity. (c) 2006 Elsevier Ltd. All rights reserved.