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

Antagonism of the human A(2A) receptor has been implicated to alleviate the symptoms associated with Parkinson's disease. The present finding reveals the potential of PUP (8-(furan-2-yl)-3-phenethylthiazolo[1,2,4]triazolo[1,5-c]pyrimidine-2(3H)-thione) as novel and potent A(2A)R antagonist. In radioligand binding assay, IMP showed significantly high binding affinity (K-1 6.3 nM) and selectivity with A(2A)R (A(1)R/A(2A)R =4603) which was comparable to the results of docking analysis (K-i = 1.6 nM, Delta G = -14.52 Kcal/mol). MP 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 MP 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 A(2A)R antagonist in the therapy of PD. (C) 2013 Elsevier Ireland Ltd. All rights reserved.