Design and synthesis of new bis-pyridinium oxime reactivators for acetyleholinesterase inhibited by organophosphorous nerve agents

被引：90

作者：

Kim, TH

Kuca, K

Jun, D

Jung, YS

机构：

[1] Korea Res Inst Chem Technol, Div Med Sci, Taejon 305606, South Korea

[2] Fac Mil Hlth Sci, Dept Toxicol, Hradec Kralove, Czech Republic

来源：

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS | 2005年 / 15卷 / 11期

关键词：

osphorus nerve agents; bis-pyridinium oxime; reactivators; inhibition; acetylcholinesterase;

D O I：

10.1016/j.bmcl.2005.03.060

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

New bis-pyridinium oxime reactivators connected with a CH2CH2OCH2 linker between two pyridinium rings were designed and synthesized. In the test of their potency to reactivate AChE inhibited by cyclosarin, the bis-pyridinium oxime 6b achieved reactivation potency higher than 10% at the lower concentration 10(-4) M. (c) 2005 Elsevier Ltd. All rights reserved.

引用

收藏

页码：2914 / 2917

页数：4

相关论文

共 22 条

[1] Organophosphates/nerve agent poisoning: Mechanism of action, diagnosis, prophylaxis, and treatment [J].

Bajgar, J .

ADVANCES IN CLINICAL CHEMISTRY, VOL. 38, 2004, 38 :151-216

[2] ACUTE AND LONG LASTING CENTRAL ACTIONS OF ORGANO-PHOSPHORUS AGENTS [J].

KARCZMAR, AG .

FUNDAMENTAL AND APPLIED TOXICOLOGY, 1984, 4 (02) :S1-S17

[3] Review of oximes in the antidotal treatment of poisoning by organophosphorus nerve agents [J].

Kassa, J .

JOURNAL OF TOXICOLOGY-CLINICAL TOXICOLOGY, 2002, 40 (06) :803-816

[4]

Kassa J, 1998, Acta Medica (Hradec Kralove), V41, P19

[5] A comparison of the efficacy of acetylcholinesterase reactivators against cyclohexyl methylphosphonofluoridate (GF agent) by in vitro and in vivo methods [J].

Kassa, J ;

Cabal, J .

PHARMACOLOGY & TOXICOLOGY, 1999, 84 (01) :41-45

[6]

Kassa J., 1997, ASA NEWSLETT, V97-4, P16

[7] Synthesis of bisquaternary symmetric -: χ,δ-bis(2-hydroxyiminomethylpyridinium) alkane dibromides and their reactivation of cyclosarin-inhibited acetylcholinesterase [J].

Kuca, K ;

Cabal, J ;

Patocka, J ;

Kassa, J .

LETTERS IN ORGANIC CHEMISTRY, 2004, 1 (01) :84-86

[8] Synthesis of a new reactivator of tabun-inhibited acetylcholinesterase [J].

Kuca, K ;

Bielavsky, J ;

Cabal, J ;

Kassa, J .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2003, 13 (20) :3545-3547

[9] A comparison of the ability of a new bispyridinium oxime-1-(4-hydroxyiminomethylpyridinium)-4-(4-carbamoylpyridinium)butane dibromide and currently used oximes to reactivate nerve agent-inhibited rat brain acetylcholinesterase by in vitro methods [J].

Kuca, K ;

Kassa, J .

JOURNAL OF ENZYME INHIBITION AND MEDICINAL CHEMISTRY, 2003, 18 (06) :529-535

[10] Synthesis of a potential reactivator of acetylcholinesterase1-(4-hydroxyiminomethylpyridinium)-3-(carbamoylpyridinium)-propane dibromide [J].

Kuca, K ;

Bielavsky, J ;

Cabal, J ;

Bielavská, M .

TETRAHEDRON LETTERS, 2003, 44 (15) :3123-3125