Novel alkyl- and arylcarbamate derivatives with N-benzylpiperidine and N-benzylpiperazine moieties as cholinesterases inhibitors

The study presents synthesis and biological activity of novel alkyl- and arylcarbamate derivatives with N-benzylpiperidine and N-benzylpiperazine moieties designed as cholinesterases inhibitors. These fragments turned out to determine compounds’ selectivity between AChE and BuChE. Derivatives of N-benzylpiperazine (16–25) were selective BuChE inhibitors with 3-(2-(4-benzylpiperazin-1-yl)-2-oxoethyl)-phenyl butylcarbamate (22) being the most potent compound (pIC50 = 5.00) while a series of carbamate derivatives of N-benzylpiperidine (5–14) displayed non-selective BuChE/AChE inhibitory activity. Molecular modelling studies point out significant differences between orientations of these two groups of compounds in the active site of AChE, which can be an explanation of their different biological activity.

Graphical abstractThis study presents a synthesis of novel carbamates and their inhibitory activity against cholinesterases.Figure optionsDownload full-size imageDownload as PowerPoint slide