The discovery and synthesis of novel adenosine receptor (A2A) antagonists

In high throughput screening of our file compounds, a novel structure 1 was identified as a potent A2A receptor antagonist with no selectivity over the A1 adenosine receptor. The structure–activity relationship investigation using 1 as a template lead to identification of a novel class of compounds as potent and selective antagonists of A2A adenosine receptor. Compound 26 was identified to be the most potent A2A receptor antagonist (Ki = 0.8 nM) with 100-fold selectivity over the A1 adenosine receptor.