Synthetic studies on selective adenosine A2A receptor antagonists: synthesis and structure-activity relationships of novel benzofuran derivatives.

A series of benzofuran derivatives were prepared to study their antagonistic activities to the A(2A) receptor. Replacement of the ester group of the lead compound 1 with phenyl ring improved the PK profile, while modifications of the amide moiety showed enhanced antagonistic activity. From these studies, compounds 13c, 13f, and 24a showed good potency in vitro and were identified as novel A(2A) receptor antagonists suitable for oral activity evaluation in animal models of catalepsy.