Biological Evaluation of Anti‐Cholinesterase Activity, in Silico Molecular Docking Studies, and DFT Calculations of Green Synthesized Thiadiazolo[3,2‐a]pyrimidine Derivatives

A series of [1,3,4] thiadiazolo[3,2‐a]pyrimidine‐6‐carboxylate derivatives 4(a–n) have been designed and synthesized as inhibitors of acetylcholinesterase (AChE). Synthesizing of thiadiazolo[3,2‐a] pyrimidines was carried out in a single step, one‐pot reaction using aromatic aldehydes, ethyl acetoacetate and different derivatives of 1,3,4‐thiadiazoles (with molar ratio of 1 : 2 : 1, respectively) in conjunction with the catalyst, anhydrous iron(III) chloride by a grinding method under solvent‐free conditions at room temperature. The in‐vitro studies exhibited good potency for inhibiting AChE comparable with donepezil as the reference drug. The best results were obtained by Ethyl 2‐(4‐nitroophenyl)‐7‐methyl‐5‐(pyridin‐3‐yl)‐5H‐[1,3,4]thiadiazolo[3,2‐a]pyrimidine‐6‐carboxylate 4n with IC50 value of 0.082±0.001 μM which was comparable with AChE inhibitory effects of donepezil (IC50=0.079 μM).