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

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

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.

Keywords: Muscle relaxant; Neuromuscular blocking agent; nAChR.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Chemistry Techniques, Synthetic
  • Male
  • Mice
  • Neuromuscular Blocking Agents / chemical synthesis*
  • Neuromuscular Blocking Agents / chemistry
  • Neuromuscular Blocking Agents / pharmacology*
  • Quaternary Ammonium Compounds / chemical synthesis*
  • Quaternary Ammonium Compounds / chemistry
  • Quaternary Ammonium Compounds / pharmacology*
  • Steroids / chemistry*
  • Structure-Activity Relationship

Substances

  • Neuromuscular Blocking Agents
  • Quaternary Ammonium Compounds
  • Steroids