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A series of novel tetrahydropyrimidin-4-yl)pyridine derivatives  6(a–h)  have been designed and synthesized as inhibitors of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE). The chemical structures of all newly synthesized compounds were characterized by spectroscopic methods (IR,  1 H NMR,  13 C NMR) and elemental analyzes. The  in vitro  studies showed that all the synthesized derivatives showed significant BChE inhibitory activity more potent than donepezil as the standard (IC 50  values less than 0.1 µM). All the target compounds demonstrated good AChE inhibitory effects comparable with donepezil as the reference drug with IC 50  values ranging from 0.08 to 0.1 µM. The best results were obtained by 4-methyl substituted derivative  6d  with IC 50  value of 0.082 µM which was comparable with AChE inhibitory effects of donepezil (IC 50  = 0.079 µM).

Design, Green Synthesis, and Biological Evaluation of New Substituted Tetrahydropyrimidine Derivatives as Acetylcholinesterase Inhibitors