Reactivation potency of fluorinated pyridinium oximes for acetylcholinesterases inhibited by paraoxon organophosphorus agent

被引：34

作者：

Jeong, Hee Chun ^{[1
,2
]}

Kang, Nam Sook ^{[1
]}

Park, No-Joong ^{[1
]}

Yum, Eul Kyun ^{[2
]}

Jung, Young-Sik ^{[1
]}

机构：

[1] Korea Res Inst Chem Technol, Drug Discovery Div, POB 107, Taejon 305600, South Korea

[2] Chungnam Natl Univ, Dept Chem, Taejon 305764, South Korea

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2009年 / 19卷 / 04期

关键词：

Organophosphorus agents; Acetylcholinesterase; Fluorinated pyridinium oxime; Oxime reactivators; DESIGN;

D O I：

10.1016/j.bmcl.2008.12.070

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

For the purpose of developing new oxime reactivators of acetylcholinesterases (AChE) that have been inhibited by organophosphorus agents, emphasis was given to the finding that the lipophilic nature of fluorinated compounds is responsible for their enhanced transport across the blood brain barrier (BBB). As a result, we have designed and synthesized the fluorinated oxime derivatives, which quantum mechanical calculations suggest should have a greater lipophilicity and BBB permeability than their non-fluorinated analogs. Among the compounds explored in this study, 4 was found to have the highest potency for reactivation of paraoxon-inhibited housefly (HF) AChE. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：1214 / 1217

页数：4

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