Recent developments in the field of A 2A and A 3 adenosine receptor antagonists

Abstract

In the last years adenosine receptors have been extensively studied, and mainly at present we understand the importance of A 2A and A 3 adenosine receptors. A 2A selective adenosine receptors antagonists are promising new drugs for the treatment of Parkinson's disease, while A 3 selective adenosine receptors antagonists have been postulated as novel anti-inflammatory and antiallergic agents; recent studies also indicated a possible employment of these derivatives as antitumour agents. Lately different classes of compounds have been identified as potent A 2A and A 3 antagonists. In this article we report the past and present efforts which led to development of more potent and selective A 2A and A 3 antagonists. Our group has mainly worked on the pyrazolo[4,3-e]-1,2,4-triazolo[1,5-c]pyrimidine nucleus both as A 2A and A 3 antagonists, aiming to improve the affinity, selectivity and the hydrophilic profile. In fact, we have synthesised several compounds endowed with high affinity and selectivity versus A 2A adenosine receptors, as 2, 2a– c ( K iA 2A=0.12–0.19 nM), or A 3 adenosine receptors, as 4p ( K iA 3=0.01 nM) and 4q ( K iA 3=0.04 nM).