Abstract：
Neuromuscular blocking agents (NMBAs) are widely used in anesthesia for intubation and surgical muscle relaxation. Novel atracurium and mivacurium derivatives were developed, with compounds 18c, 18d, and 29a showing mivacurium-like relaxation at 27.27 nmol/kg, and 15b, 15c, 15e, and 15h having a shorter duration at 272.7 nmol/kg. The structure-activity and configuration-activity relationships of these derivatives and 29a\'s binding to nicotinic acetylcholine receptors were analyzed through molecular docking. Rabbit trials showed 29a has a shorter duration compared to mivacurium. This suggests that linker properties, ammonium group substituents, and configuration are crucial for NMBA activity and duration, with compound 29a emerging as a potential ultra-short-acting NMBA.
摘要：
神经肌肉阻断剂（NMBAs）广泛用于插管和手术肌肉松弛的麻醉。开发了新型阿曲库铵和米伐库铵衍生物，化合物18c,18d,和29a在27.27nmol/kg时显示米伐库铵样松弛，15b,15c,15e,和15h,在272.7nmol/kg下具有较短的持续时间。通过分子对接分析了这些衍生物的结构-活性和构型-活性关系以及29a与烟碱乙酰胆碱受体的结合。家兔试验显示，与米伐库铵相比，29a的持续时间较短。这表明链接器属性，铵基取代基，配置对于NMBA的活动和持续时间至关重要，化合物29a成为潜在的超短效NMBA。
