作为神经肌肉阻滞剂的3,16-双季铵甾体衍生物：合成与生物学评价

3,16-Bisquaternary ammonium steroid derivatives as neuromuscular blocking agents: synthesis and biological evaluation.

作者信息

Hu Hao, Rao Zhigang, Feng Min, Wu Zhe, Xu Jianrong, Chen Hongzhuan, Liu Peng, Xiao Yuling, Hong Xuechuan, Hu Xianming, Ke Xianbing

机构信息

State Key Laboratory of Virology, Ministry of Education Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Wuhan University School of Pharmaceutical Sciences, Wuhan 430071, China.

Department of Pharmacology, Institute of Medical Sciences, Shanghai Jiao Tong University School of Medicine, Shanghai 200025, China.

出版信息

Steroids. 2015 Apr;96:103-14. doi: 10.1016/j.steroids.2015.01.008. Epub 2015 Jan 29.

DOI:10.1016/j.steroids.2015.01.008

PMID:25637675

Abstract

Neuromuscular blocking agents (NMBAs) are widely used in surgery to achieve skeleton muscles relaxation under light anesthesia status. In this work, we synthesized a series of 3,16-bisquaternary ammonium steroidal NMBAs. Among them, three compounds exhibited higher in vitro activities than the commenced drug rocuronium. In addition, structure-activity relationship was unveiled. We found that the intact acetylcholine-like moiety in D-ring was not necessary for maintaining activity but both the acetyl group and the quaternary nitrogen were very essential.

摘要

神经肌肉阻滞剂（NMBAs）在手术中被广泛应用，以在浅麻醉状态下实现骨骼肌松弛。在本研究中，我们合成了一系列3,16-双季铵甾体NMBAs。其中，三种化合物表现出比起始药物罗库溴铵更高的体外活性。此外，还揭示了构效关系。我们发现D环中完整的乙酰胆碱样部分对于维持活性并非必需，但乙酰基和季铵氮两者都非常重要。