Synthesis of novel 7-imino-2-thioxo-3,7-dihydro-2H-thiazolo [4,5-d] pyrimidine derivatives as adenosine A2A receptor antagonists

Novel bicyclic thiazolopyrimidine compounds (15–26) were synthesized to develop adenosine A2A receptor (A2AR) antagonist for the treatment of Parkinson’s disease (PD). The binding affinity of the compounds (15–26) with A2AR was evaluated using radioligand binding assay on isolated membranes from stably transfected HEK293 cells. Selectivity of the compounds towards A2AR was assessed by comparing their binding affinities with A1 receptors (A1R). cAMP concentrations were measured from HEK293 cells treated with compounds (15–26) as compared to NECA (A2AR agonist). The compound (16) possessed strongest A2AR binding affinity (Ki value = 0.0038 nM) and selectivity (737-fold) versus A1R. Decrease in A2AR-coupled release of endogenous cAMP from HEK293 cells treated with compounds (15–26) is evocative of their potential as A2AR antagonist.

Novel bicyclic thiazolopyrimidine compounds (15–26) were synthesized and their in vitro binding studies and functional assay (cAMP determination) showed that compound (16) is a potent and selective A2AR antagonist with strong binding affinity (Ki value = 0.0038 nM) towards A2AR and higher selectivity (737-fold) versus A1R.Figure optionsDownload as PowerPoint slide