Replacement of amide with bioisosteres led to a new series of potent adenosine A2A receptor antagonists

We have previously reported a series of 2,4,6-trisubstituted pyrimidines as potent A(2A) receptor antagonists. The leading compounds often feature a potentially labile acetamide functional group which tends to hydrolyze under acidic conditions. Here we report the replacement of the acetamide functional group with bioisosteres. This effort led us to a new series of adenosine A(2A) receptor antagonists with improved potency and chemical stability. (C) 2013 Elsevier Ltd. All rights reserved.