Synthesis and screening for antiacetylcholinesterase activity of (1-benzyl-4-oxopiperidin-3-ylidene)methylindoles and -pyrroles related to donepezil

The design, synthesis, and rapid evaluation of a new class of acetylcholine sterase (AChE) inhibitors related to donepezil are reported. A molecular dy namics simulation of the complex between AChE and one representative compou nd of the series showed a possible inhibitor binding mode in which favorabl e interactions are formed between the benzylpiperidinone moiety and some ac tive-site residues. The biochemical evaluation of this newly synthesized se ries was performed using a chemiluminescent method suitable for high-throug hput screening.