[摘要]：Antagonism of the human A2A receptor has been implicated as a point of therapeutic intervention in the alleviation of the symptoms assocd. with Parkinson's disease. This is thought to occur, at least in part, by increasing the sensitivity of the dopaminergic neurons to the residual, depleted levels of striatal dopamine. We herein describe a novel series of functionalized triazolo[4,5-d]pyrimidine derivs. that display functional antagonism of the A2A receptor. Optimization of these compds. has resulted in improvements in potency, selectivity, and the pharmacokinetic properties of key derivs. These efforts have led to the discovery of I (V2006/BIIB014), which demonstrates strong oral activity in commonly used models of Parkinson's disease. Furthermore, this deriv. has shown excellent preclin. pharmacokinetics and has successfully completed phase I clin. studies. This compd. is presently undergoing further clin. evaluation in collaboration with Biogen Idec.
