Department of Chemistry, The University of Iowa, Iowa City, Iowa 52242, USA.
Org Lett. 2013 Mar 1;15(5):1084-7. doi: 10.1021/ol400054m. Epub 2013 Feb 14.
Organophosphate nerve agents and pesticides are potent inhibitors of acetylcholinesterase (AChE). Although oxime nucleophiles can reactivate the AChE-phosphyl adduct, the adduct undergoes a reaction called aging. No compounds have been described that reactivate the aged-AChE adduct. A family of 2-methoxypyridinium species which reverse aging in a model system is presented. A kinetic study of this system, which includes an SAR analysis, demonstrates that the reaction is highly tunable based on the ring substituents.
有机磷神经毒剂和杀虫剂是乙酰胆碱酯酶 (AChE) 的强效抑制剂。尽管肟亲核试剂可以使 AChE-膦酰化加合物重新活化,但该加合物会发生称为老化的反应。尚未描述能使老化的 AChE 加合物重新活化的化合物。本文介绍了一类可使模型系统中老化逆转的 2-甲氧基吡啶鎓化合物。对该体系的动力学研究(包括 SAR 分析)表明,该反应可通过环取代基高度调控。