Optimization of arylindenopyrimidines as potent adenosine A(2A)/A(1) antagonists.

Abstract Two reactive metabolites were identified in vivo for the dual A 2A /A 1 receptor antagonist 1 . Two strategies were implemented to successfully mitigate the metabolic liabilities associated with 1 . Optimization of the arylindenopyrimidines led to a number of amide, ether, and amino analogs having comparable in vitro and in vivo activity.