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

• Three compounds exhibited higher in vitro activity than rocuronium.
• Structure–activity relationship was studied via calculated N–N distance and log P.
• Increasing hydrophobicity of 3-amine leads to better activity.
• Intact acetylcholine-like moiety in D-ring is important but not necessary for best activity.
• Acetyl group and quaternary nitrogen in D-ring are very essential.

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.

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