Antagonists of the human adenosine A2A receptor. Part 2: Design and synthesis of 4-arylthieno[3,2-d]pyrimidine derivatives

We describe herein the discovery and development of a series of 4-arylthieno(3,2-d)pyrimidines which are potent adeno- sine A2A receptor antagonists. These novel compounds show high degrees of selectivity against the human A1 ,A 2B and A3 receptor sub-types. Moreover, a number of these compounds show promising activity in vivo, suggesting potential utility in the treatment of Parkinson's disease. 2008 Elsevier Ltd. All rights reserved. Adenosine receptors comprise four distinct sub-types, designated A1 ,A 2A ,A 2B and A3. In the brain, adenosine A2A receptors are located primarily in the striatum, playing a key role in regulating movement. There is strong evidence that adenosine A2A receptor antagonists may provide a novel therapy for the treatment of Par- kinson's disease, with a lower risk of dyskinesias. 1