Synthesis and anticholinesterase activity of huperzine A analogues containing phenol and catechol replacements for the pyridone ring

被引：34

作者：

Campiani, G

Kozikowski, AP

Wang, SM

Ming, L

Nacci, V

Saxena, A

Doctor, BP

机构：

[1] Univ Siena, Dipartimento Farm Chim Tecnol, I-53100 Siena, Italy

[2] Georgetown Univ, Med Ctr, Drug Discovery Program, Inst Cognit & Computat Sci, Washington, DC 20007 USA

[3] Walter Reed Army Inst Res, Div Biochem, Washington, DC 20307 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 1998年 / 8卷 / 11期

关键词：

D O I：

10.1016/S0960-894X(98)00229-7

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Based upon modeling results obtained using the crystal structure of huperzine A in complex with acetylcholinesterase (AChE), two novel analogues of this potent AChE inhibitor were designed with phenol or catechol rings replacing the pyridone ring. From the modeling studies, the catechol analogue appeared capable of replacing one of the crystallographic waters bridging huperzine with Tyr 130 and Glu 199 of AChE. The synthesis of these materials by use of a palladium catalyzed bicycloannulation strategy is detailed together with the results of AChE inhibition assays. (C) 1998 Elsevier Science Ltd. All rights reserved.

引用

页码：1413 / 1418

页数：6

共 26 条

[1] MECHANISM OF INHIBITION OF CHOLINESTERASES BY HUPERZINE-A [J].