Abstract：
The first organophosphorus nerve agent was discovered accidently during the development of pesticides, shortly after the first use of chemical weapons (chlorine, phosgene) on the battlefield during World War I. Despite the Chemical Weapons Convention banning these substances, they have still been employed in wars, terrorist attacks or political assassinations. Characterised by their high lethality, they target the nervous system by inhibiting the acetylcholinesterase (AChE) enzyme, preventing neurotransmission, which, if not treated rapidly, inevitably leads to serious injury or the death of the person intoxicated. The limited efficacy of current antidotes, known as AChE reactivators, pushes research towards new treatments. Numerous paths have been explored, from modifying the original pyridinium oximes to developing hybrid reactivators seeking a better affinity for the inhibited AChE. Another crucial approach resides in molecules more prone to cross the blood-brain barrier: uncharged compounds, bio-conjugated reactivators or innovative formulations. Our aim is to raise awareness on the threat and toxicity of organophosphorus nerve agents and to present the main synthetic efforts deployed since the first AChE reactivator, to tackle the task of efficiently treating victims of these chemical warfare agents.
摘要：
在农药开发过程中偶然发现了第一种有机磷神经毒剂，在首次使用化学武器(氯，光气）在第一次世界大战期间的战场上，尽管《化学武器公约》禁止这些物质，他们仍然受雇于战争，恐怖袭击或政治暗杀。以它们的高杀伤力为特征，它们通过抑制乙酰胆碱酯酶（AChE）酶靶向神经系统，阻止神经传递,which,如果不迅速治疗，不可避免地导致重伤或醉酒的人死亡。目前解毒剂的功效有限，被称为AChE激活剂，推动研究转向新的治疗方法。已经探索了许多路径，从修饰原始的吡啶肟到开发混合活化剂，以寻求对抑制的AChE的更好亲和力。另一个关键的方法在于分子更容易穿过血脑屏障：不带电荷的化合物，生物共轭活化剂或创新配方。我们的目标是提高对有机磷神经毒剂的威胁和毒性的认识，并介绍自第一个AChE再激活器以来部署的主要合成工作，解决有效治疗这些化学战剂受害者的任务。
