Design and development of 1,3,5-triazine-thiadiazole hybrids as potent adenosine AA receptor (AAR) antagonist for benefit in Parkinson's disease.

Various studies showed adenosine AA receptors (AARs) antagonists have profound therapeutic efficacy in Parkinsons Disease (PD) by improving dopamine transmission, thus being active in reversing motor deficits and extrapyramidal symptoms related to the disease. Therefore, in the presents study, we have showed the development of novel 1,3,5-triazine-thiadiazole derivative as potent AARs antagonist. In the radioligand binding assay, these molecules showed excellent binding affinity with AAR compared to AR, with significant selectivity. Results suggest, compound 7e as most potent antagonist of AAR among the tested series. In docking analysis with AAR protein model, compound 7e found to be deeply buried into the cavity of receptor lined via making numerous interatomic contacts with His264, Tyr271, His278, Glu169, Ala63, Val84, Ile274, Met270, Phe169. Collectively, our study demonstrated 1,3,5-triazine-thiadiazole hybrid as a highly effective scaffold for the design of new AA antagonists.