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

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• 作者：Anna Wię ; ckowska ; Marek Bajda ; Natalia Guzior ; Barbara Malawska
• 关键词：Acetylcholinesterase inhibitors ; Butyrylcholinesterase inhibitors ; Carbamate derivatives ; Alzheimer’ ; s disease
• 刊名：European Journal of Medicinal Chemistry
• 出版年：2010
• 出版时间：December 2010
• 年：2010
• 卷：45
• 期：12
• 页码：5602-5611
• 全文大小：1058 K

文摘

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.