Tacrine based human cholinesterase inhibitors: Synthesis of peptidic-tethered derivatives and their effect on potency and selectivity

被引：29

作者：

Butini, Stefania ^{[1
,2
]}

Guarino, Egeria ^{[1
,2
]}

Campiani, Giuseppe ^{[1
,2
]}

Brindisi, Margherita ^{[1
,2
]}

Coccone, Salvatore Sanna ^{[1
,2
]}

Fiorini, Isabella ^{[1
,2
]}

Novellino, Ettore ^{[2
,3
]}

Belinskaya, Tatyana ^{[4
]}

Saxena, Ashima ^{[4
]}

Gemma, Sandra ^{[1
,2
]}

机构：

[1] Univ Siena, Dipartimento Farmaco Chimico Tecnol, I-53100 Siena, Italy

[2] European Res Ctr Drug Discovery & Dev NatSynDrugs, I-53100 Siena, Italy

[3] Univ Naples Federico 2, Dip Chim Farmaceut & Tossicolog, I-80131 Naples, Italy

[4] Walter Reed Army Inst Res, Div Biochem, Silver Spring, MD 20910 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2008年 / 18卷 / 19期

关键词：

cholinesterases; Alzeheimer's disease; inhibitors; tacrine;

D O I：

10.1016/j.bmcl.2008.08.076

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Tacrine based reversible inhibitors of cholinesterases (ChEIs) containing peptidic tethers were synthesized to interact with specific regions at the gorge level, and their potency was determined with human ( h) acetylcholinesterase and butyrylcholinesterase. Analogues 3ij and 31,m were identified as promising hits and may pave the way for the development of a new series of tacrine based enzyme selective hChEIs. (C) 2008 Elsevier Ltd. All rights reserved.

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页码：5213 / 5216

页数：4

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