Organophosphate (OP) causes phosphorylation of acetylcholinesterase enzyme which leads to accumulation of acetylcholine. This phosphorylation generally occurs due to exposure of nerve agents and intake of pesticides, etc. Various standard drugs specifically oxime derivatives (HI-6, Obidoxime, 2-PAM, etc.) are used as AChE enzyme reactivation agents. These standard drugs show least penetration to CNS. Taking them into consideration with the help of structure and ligand based screened compounds, various small molecules analogues targeting CNS have been designed. These analogues pass all the pharmacokinetic parameters structurally and have also shown better results than that of standards. Among various charged and uncharged analogues, 4g, 4h and 4j have attained docking scores –13.11, –12.84 and –12.75Kcal/mol respectively which is better than that of the standard (HI-6) –12.13kcal/mol.

中文翻译：

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乙酰胆碱酯酶去磷酸化的类似物设计

有机磷 (OP) 会引起乙酰胆碱酯酶的磷酸化，从而导致乙酰胆碱的积累。这种磷酸化通常是由于暴露于神经毒剂和摄入杀虫剂等而发生的。各种标准药物特别是肟衍生物（HI-6、Obidoxime、2-PAM 等）被用作 AChE 酶再激活剂。这些标准药物对 CNS 的渗透性最低。在基于结构和配体的筛选化合物的帮助下考虑到它们，已经设计了各种靶向 CNS 的小分子类似物。这些类似物在结构上通过了所有药代动力学参数，并且还显示出比标准品更好的结果。在各种带电和不带电类似物中，4g、4h 和 4j 的对接分数分别为 –13.11、–12.84 和 –12。