8-(Furan-2-yl)-3-phenethylthiazolo[5,4-e][1,2,4]triazolo[1,5-c]pyrimidine-2(3H)-thione as novel, selective and potent adenosine A2A receptor antagonist
文摘
Antagonism of the human A2A receptor has been implicated to alleviate the symptoms associated with Parkinson's disease. The present finding reveals the potential of PTTP (8-(furan-2-yl)-3-phenethylthiazolo[1,2,4]triazolo[1,5-c]pyrimidine-2(3H)-thione) as novel and potent A2AR antagonist. In radioligand binding assay, PTTP showed significantly high binding affinity (Ki 6.3 nM) and selectivity with A2AR (A1R/A2AR = 4603) which was comparable to the results of docking analysis (Ki = 1.6 nM, 螖G = 鈭?4.52 Kcal/mol). PTTP antagonized (0.46 pmol/ml) the effect of NECA-induced increase in cAMP concentration (0.65 pmol/ml) better than SCH58261 (0.55 pmol/ml) in HEK293 T cells. Haloperidol and NECA-induced mice pre-treated with PTTP at 10 mg/kg showed attenuation in catalepsy and akinesia without significant neurotoxicity in rotarod test at 20 mg/kg. Essentially, novel compound demonstrated remarkable potential as A2AR antagonist in the therapy of PD.