Synthesis and pharmacological evaluation of huprine-tacrine heterodimers:: Subnanomolar dual binding site acetylcholinesterase inhibitors

被引：80

作者：

Camps, P

Formosa, X

Muñoz-Torrero, D

Petrignet, J

Badia, A

Clos, MV

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

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2005年 / 48卷 / 06期

关键词：

D O I：

10.1021/jm0496741

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of huprine-tacrine heterodimers has been developed by connection of huprine Y, a compound with one of the highest affinities for the active site of acetyleholinesterase yet reported, with tacrine, a compound with known affinity for the peripheral site of the enzyme, through a linker of appropriate length to allow simultaneous interaction with both binding sites. These compounds exhibit human acetylcholinesterase and butyrylcholinesterase inhibitory activities with IC50 values in the subnanomolar and low nanomolar range, respectively.

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页码：1701 / 1704

页数：4

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