Design of a potent reactivator of tabun-inhibited acetyleholinesterase-synthesis and evaluation of (E)-1-(4-carbamoylpyridinium)-4-(4-hydroxyiminomethylpyridinium)-but-2-ene dibromide (K203)

被引:105
作者
Musilek, Kamil
Jun, Daniel
Cabal, Jiri
Kassa, Jiri
Gunn-Moore, Frank
Kuca, Kamil [1 ]
机构
[1] Univ St Andrews, Sch Biol, St Andrews KY16 9AJ, Fife, Scotland
[2] Univ Def, Fac Mil Hlth Sci, Ctr Adv Studies, Dept Toxicol, Hradec Kralove 50001, Czech Republic
[3] Charles Univ Prague, Fac Pharm, Dept Pharmaceut Chem & Drug Control, Prague 50005, Czech Republic
基金
英国医学研究理事会;
关键词
D O I
10.1021/jm070653r
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Acetylcholinesterase reactivators are crucial antidotes for the treatment of organophosphate intoxication. Among the organophosphates, with the exception of soman, tabun (GA) intoxications are the least responsive to treatment with commercially available therapeutics. A rational design was used to increase reactivation ability and decrease the toxicity of the novel reactivator. (E)-1-(4-carbamoylpyridinium)-4-(4-hydroxyiminomethylpyridinium)-but-2-ene dibromide (K203) has better properties than previously tested compounds in vitro and, therefore, is a potential candidate for the treatment of GA intoxication in vivo.
引用
收藏
页码:5514 / 5518
页数:5
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