作者
Maria Laura Bolognesi, Manuela Bartolini, Andrea Cavalli, Vincenza Andrisano, Michela Rosini, Anna Minarini, Carlo Melchiorre
发表日期
2004/11/18
期刊
Journal of medicinal chemistry
卷号
47
期号
24
页码范围
5945-5952
出版商
American Chemical Society
简介
Rivastigmine (1), an acetylcholinesterase (AChE) inhibitor approved in 2000 for the treatment of Alzheimer disease, bears a carbamate moiety in its structure, which is able to react covalently with the active site of the enzyme. Kinetic and structural studies on the interaction of 1 with different cholinesterases have been published, giving deeper, but not definitive, insights on the catalysis mechanism. On the basis of these findings and in connection with our previous studies on a series of benzopyrano[4,3-b]pyrrole carbamates as AChE inhibitors, we designed a series of conformationally restricted analogues of 1 by including the dimethylamino-α-methylbenzyl moiety in different tricyclic systems. A superimposition between the conformation of 1 and the carbon derivative 4, as obtained from Monte Carlo simulations, supported the idea that the tricyclic derivatives might act as rigid analogues of 1. The biological profile of …
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ML Bolognesi, M Bartolini, A Cavalli, V Andrisano… - Journal of medicinal chemistry, 2004