Synthesis of [1,2,4]triazolo[1,5-a]pyrazines as adenosine A2A receptor antagonists.

Abstract Potent and selective antagonists of the adenosine A 2A receptor often contain a nitrogen-rich fused-ring heterocyclic core. Replacement of the core with an isomeric ring system has previously been shown to improve target affinity, selectivity, and in vivo activity. This paper describes the preparation, by a novel route, of A 2A receptor antagonists containing the [1,2,4]triazolo[1,5- a ]pyrazine nucleus, which is isomeric with the [1,2,4]triazolo[1,5- c ]pyrimidine core of a series of known A 2A antagonists with in vivo activity in animal models of Parkinson’s disease.