Discovery of Potent and Selective A_2A Antagonists with Efficacy in Animal Models of Parkinson's Disease and Depression.

ABSTRACT: Adenosine A_2A receptor (A_2AAdoR) antagonism is a nondopaminergic approach to Parkinson's disease treatment that is under development. Earlier we had reported the therapeutic potential of 7-methoxy-4-morpholino-benzothiazole derivatives as A_2AAdoR antagonists. We herein described a novel series of [1,2,4]triazolo[5,1-f]purin-2-one derivatives that displays functional antagonism of the A_2A receptor with a high degree of selectivity over A₁, A_2B, and A₃ receptors. Compounds from this new scaffold resulted in the discovery of highly potent, selective, stable, and moderate brain penetrating compound 33. Compound 33 endowed with satisfactory in vitro and in vivo pharmacokinetics proper

SUBMITTER: Basu S 

PROVIDER: S-EPMC5554908 | biostudies-literature | 2017 Aug

REPOSITORIES: biostudies-literature