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 acetylcholinesterase (AChE) inhibitors related to donepezil are reported. A molecular dynamics simulation of the complex between AChE and one representative compound of the series showed a possible inhibitor binding mode in which favorable interactions are formed between the benzylpiperidinone moiety and some active-site residues. The biochemical evaluation of this newly synthesized series was performed using a chemiluminescent method suitable for high-throughput screening.