Synthesis of alkyne derivatives of a novel triazolopyrazine as A2A adenosine receptor antagonists

A novel [1,2,4]triazolo[1,5-a]pyrazine core was synthesized and coupled with terminal acetylenes. The structure–activity relationship of the alkynes from this novel template was studied for their in vitro and in vivo adenosine A2A receptor antagonism. Selected compounds from this series were shown to have potent in vitro and in vivo activities against adenosine A2A receptor. Compound 12, in particular, was found to be orally active at 3 mg/kg in both a mouse catalepsy model and a 6-hydroxydopamine-lesioned rat model.