Novel 2-thioxothiazole derivatives (6-19) as potential adenosine A2A receptor (A2AR) antagonists were synthesized. The strong interaction of the compounds (6-19) with A2AR in docking study was confirmed by high binding affinity with human A2AR expressed in HEK293T cells using radioligand-binding assay. The compound 19 demonstrated very high selectivity for A2AR as compared to standard A2AR antagonist SCH58261. Decrease in A2AR-coupled release of endogenous cAMP in treated HEK293T cells demonstrated in vitro A2AR antagonist potential of the compound 19. Attenuation in haloperidol-induced impairment (catalepsy) in Swiss albino male mice pre-treated with compound 19 is evocative to explore its prospective in therapy of PD.
Keywords: 2-Thioxothiazole; A(2A)R antagonist; Haloperidol; Radioligand-binding assay; cAMP assay.
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