N-benzylpiperidine derivatives of 1,2,4-thiadiazolidinone as new acetylcholinesterase inhibitors

A new family of 1,2,4-thiadiazolidinone derivatives containing the N-benzyl piperidine fragment has been synthesised. The acetylcholinesterase (AChE) i nhibitory activity of all compounds was measured using Ellman's method and some of them turned out to be as potent as tacrine. Furthermore, compound 1 3 was as active as tacrine in reversing the blockade induced by tubocurarin e at rat neuromuscular junction. Additionally, receptor binding studies pro vided new lead compounds for further development of alpha (2)-adrenergic an d sigma-receptor antagonists. Molecular dynamic simulation using X-ray crys tal structure of AChE from Torpedo californica was used to explain the poss ible binding mode of these new compounds. (C) 2000 Editions scientifiques e t medicales Elsevier SAS.