Design, synthesis, and characterization of novel, nonquaternary reactivators of GF-inhibited human acetylcholinesterase

被引：20

作者：

McHardy, Stanton F. ^{[1
]}

Bohmann, Jonathan A. ^{[1
]}

Corbett, Michael R. ^{[1
]}

Campos, Bismarck ^{[1
]}

Tidwell, Michael W. ^{[1
]}

Thompson, Paul Marty ^{[1
]}

Bemben, Chris J. ^{[1
]}

Menchaca, Tony A. ^{[1
]}

Reeves, Tony E. ^{[1
]}

Cantrell, William R., Jr. ^{[1
]}

Bauta, William E. ^{[1
]}

Lopez, Ambrosio ^{[1
]}

Maxwell, Donald M. ^{[2
]}

Brecht, Karen M. ^{[2
]}

Sweeney, Richard E. ^{[2
]}

McDonough, John ^{[2
]}

机构：

[1] SW Res Inst, Chem & Chem Engn Div, Dept Med & Proc Chem, San Antonio, TX 78266 USA

[2] Pharmacol Branch, USAMRICD Res Div, Aberdeen Proving Ground, MD 21010 USA

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2014年 / 24卷 / 07期

关键词：

Acetylcholinesterase; Reactivation; Cyclosarin (GF); GF-inhibited hAChE; Structure-activity relationship; Heteroaryl keto-oximes; ACTING OXIME REACTIVATORS; THERAPEUTIC-EFFICACY; NERVE AGENTS; DELIVERY; KETONES;

D O I：

10.1016/j.bmcl.2014.02.049

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

The goal of this research was to identify structurally novel, non-quaternarypyridinium reactivators of GF (cyclosarin)-inhibited hAChE that possess the capacity to mediate in vitro reactivation of GF-inhibited human acetylcholinesterase (hAChE). New compounds were designed, synthesized and assessed in GFinhibited hAChE assays. Structure activity relationships for AChE binding and reactivation of GF-inhibited hAChE were developed. Lead compounds from two different chemical series, represented by compounds 17 and 38, displayed proficient in vitro reactivation of GF- inhibited hAChE, while also possessing low inhibition of native enzyme. (c) 2014 Elsevier Ltd. All rights reserved.

引用

页码：1711 / 1714

页数：4

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