Facile synthesis of fused 1,2,4-triazolo[1,5-c]pyrimidine derivatives as human adenosine A3 receptor ligands

A facile synthetic method for fused triazolopyrimidine derivatives having high affinity and selectivity for human adenosine A3 receptors is reported. The fused triazolopyrimidine derivatives were easily prepared by one-pot reaction using acylhydrazines and imidates prepared from amine derivatives bearing cyano group and orthoesters in situ. This synthetic method was useful in finding new tricyclic adenosine A3 receptor antagonists and also in diversifying the substituents at two positions on the fused triazolopyrimidine ring.