Synthesis, in vitro pharmacology, and molecular modeling of syn-huprines as acetylcholinesterase inhibitors

被引：61

作者：

Camps, P

Gómez, E

Muñoz-Torrero, D

Badia, A

Vivas, NM

Barril, X

Orozco, M

Luque, FJ

机构：

[1] Univ Barcelona, Fac Farm, Quim Farmaceut Lab, E-08028 Barcelona, Spain

[2] Univ Autonoma Barcelona, Fac Med, Dept Farmacol & Terapeut, E-08193 Barcelona, Spain

[3] Univ Barcelona, Fac Farm, Dept Fisicoquim, E-08028 Barcelona, Spain

[4] Univ Barcelona, Fac Quim, Dept Bioquim, E-08028 Barcelona, Spain

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2001年 / 44卷 / 26期

关键词：

D O I：

10.1021/jm010949b

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Two 12-amino-6,7,8,11-tetrahydro-7,11-methanocycloocta[b]quinoline derivatives [9-Me(Et)] (syn-huprines) have been obtained by condensation of known 7-alkylbicyclo[3.3.1]non-6-en-3ones with 2-(trifluoromethyl)aniline, followed by basic cyclization of the resulting imine, and chromatographic separation of the regioisomeric mixture of products, thus obtained. The new (+/-)-syn-huprines were shown to be slightly less active bovine or human acetylcholinesterase inhibitors than the corresponding anti-derivatives. Molecular modeling simulations allow us to explain the differences in inhibitory activity of these compounds on the basis of an inverse solvation effect.

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收藏

页码：4733 / 4736

页数：4

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