title: Steroidal Ammonium Compounds as New Neuromuscular Blocking Agents.
abstract: Neuromuscular blocking agents are widely used as an anesthesia auxiliary in surgery, which induce relaxation of skeletal muscles by blocking signal transmission at the neuromuscular junction. Many neuromuscular blocking agents s were developed over the past decades, but none of them fully meets the needs of the clinic by various reasons. In this study, a series of quaternary ammonium steroidal neuromuscular blocking agents were synthesized and evaluated on isolated mouse phrenic nerve-hemidiaphragms for their bioactivities. The initial separation of mono- and bis-quaternary ammonium compounds turned out to be very challenging on regular silica gel chromatography. Therefore, a facile purification method, in which the silica gel was pretreated with methanolic sodium bromide solution, was finally achieved. Compounds 3g (0.36 μm) and 4g (0.37 μm) exhibited excellent neuromuscular blocking activities, which were about sixfold to sevenfold higher in potency than that of rocuronium (2.50 μm). In addition, other bis-quaternized compounds also showed good potencies close to that of rocuronium. Furthermore, the preliminary structure-activity relationship of this series was also elucidated. Benzyl group was found to be a promising quaternary group in this series.
authors.affiliation: 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.
authors.forename: Zhigang
authors.initials: Z
authors.lastname: Rao
authors.affiliation: 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.
authors.forename: Hao
authors.initials: H
authors.lastname: Hu
authors.affiliation: 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.
authors.forename: Jiazhi
authors.initials: J
authors.lastname: Tang
authors.affiliation: 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.
authors.forename: Zhiying
authors.initials: Z
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Yue
authors.initials: Y
authors.lastname: Yang
authors.affiliation: 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.
authors.forename: Guofu
authors.initials: G
authors.lastname: Qiu
authors.affiliation: 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.
authors.forename: Yuling
authors.initials: Y
authors.lastname: Xiao
authors.affiliation: 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.
authors.forename: Peng
authors.initials: P
authors.lastname: Liu
authors.affiliation: 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.
authors.forename: Xianming
authors.initials: X
authors.lastname: Hu
authors.affiliation: 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.
authors.forename: Xiaoju
authors.initials: X
authors.lastname: Zhou
authors.affiliation: 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.
authors.forename: Xuechuan
authors.initials: X
authors.lastname: Hong
mesh_terms: D064751:Ammonium Compounds / Q000494:pharmacology*; D009682:Magnetic Resonance Spectroscopy; D009466:Neuromuscular Blocking Agents / Q000494:pharmacology*; D021241:Spectrometry, Mass, Electrospray Ionization; D013256:Steroids / Q000494:pharmacology*
chemical_list: D064751:Ammonium Compounds; D009466:Neuromuscular Blocking Agents; D013256:Steroids
keywords: ion chromatography; muscle relaxant; neuromuscular blocking agents; steroidal ammonium separation