苯基二正戊基次膦酸酯：一种用于研究神经病变靶酯酶（NTE）以及预防有机磷酸酯诱导的迟发性多发性神经病的便捷可再活化抑制剂。

Phenyl di-n-pentylphosphinate: a convenient reactivatible inhibitor for studies on neuropathy target esterase (NTE) and protection against organophosphate-induced delayed polyneuropathy.

作者信息

Johnson M K, Bird I, Meredith C

机构信息

MRC Toxicology Unit, Medical Research Council Laboratories, Carshalton, Surrey, U.K.

出版信息

Toxicol Lett. 1988 Feb;40(2):133-40. doi: 10.1016/0378-4274(88)90154-3.

DOI:10.1016/0378-4274(88)90154-3

PMID:2829392

Abstract

Phenyl di-n-pentylphosphinate was synthesised by interaction of phenyl phosphorodichloridate and n-pentyl magnesium bromide. The product was purified by silica chromatography (yield 25%). Although much more stable at physiological pH than its 4-nitrophenyl analogue, this ester is a good inhibitor of neuropathy target esterase (NTE): kappa a = 1.7 X 10(5) M-1 min-1. It is a very weak anticholinesterase (kappa a congruent to 10 M-1 min-1). In vivo only 5-10 mg/kg is required to inhibit hen brain and spinal cord NTE. The inhibited NTE can be reactivated fully by incubation in vitro with iso-nitrosoacetophenone (INAP) (19 mM at 37 degrees C and pH 8.5 for 60 min): this property enables study to be made of the fate of inhibited NTE in vivo.

摘要

通过苯基二氯磷酸酯与正戊基溴化镁反应合成了苯基二正戊基次膦酸酯。产物通过硅胶柱色谱法纯化（产率25%）。尽管该酯在生理pH下比其4-硝基苯基类似物稳定得多，但它是神经病变靶标酯酶（NTE）的良好抑制剂：κa = 1.7×10⁵ M⁻¹ min⁻¹。它是一种非常弱的抗胆碱酯酶（κa≈10 M⁻¹ min⁻¹）。在体内，仅需5 - 10 mg/kg就能抑制母鸡脑和脊髓中的NTE。通过在体外与异亚硝基苯乙酮（INAP）（37℃、pH 8.5下19 mM，孵育60分钟）孵育，被抑制的NTE可被完全重新激活：这一特性使得能够研究体内被抑制的NTE的命运。