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本文根据新的重活化理论模型讨论了季铵和非季铵两类重活化剂的构效关系及其作用机理。在构效关系研究基础上,对重活化剂的分子结构进行了基本设计:(1)最好是叔胺型,不仅有利于通过血脑屏障,进入中枢,更有利于药物与受体之间的轨道作用,季铵的电荷作用太强,不利于轨道作用的充分发挥。(2)应该存在足够大的π-π共轭体系,具有较高的HOMO能级或较低的LUMO能级。(3)活性基团之间的距离,肟基氧到季铵或叔胺氮的距离D1应接近3—6;π-π共轭体系到肟羟基氧的距离D2约为7—10。(4)活性基团最好是柔性结构(有利于构象调节),构象改变又不要明显地影响前线轨道能级的变化(以保持轨道作用的最佳状态)。
In this paper, based on the new reactivation theory model, the structure-activity relationship and its mechanism of the two kinds of activators of quaternary ammonium and non-quaternary ammonium are discussed. Based on the study of structure-activity relationship, the basic design of the molecular structure of the activator is designed: (1) It is best to be a tertiary amine, which not only helps to get through the blood-brain barrier and enter the center, Orbit, quaternary ammonium charge is too strong, is not conducive to the full orbit. (2) There should be a sufficiently large π-π conjugated system with either a higher HOMO level or a lower LUMO level. (3) the distance between the active groups, the distance D1 between the oxime oxygen and the quaternary ammonium or the tertiary amine nitrogen should be close to 3-6; and the distance D2 between the π-π conjugated system and the oxime oxygen is about 7-10. (4) The active group is preferably a flexible structure (favoring the conformational regulation) and the conformational change does not significantly affect the change in the frontier orbital energy level (in order to maintain the orbital optimum).