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  3. Design, synthesis and biological evaluation of novel procaine derivatives for intravenous anesthesia

Design, synthesis and biological evaluation of novel procaine derivatives for intravenous anesthesia

  • Bioorg Med Chem Lett. 2022 Mar 15;60:128587. doi: 10.1016/j.bmcl.2022.128587.
Jiaqi Yin 1,  Yi Zhao 2,  Qian He 3,  Ao Hai 2,  Yanlai Peng 1,  Zeping Zuo 2,  Zhenlei Song 4,  Bowen Ke 2
Affiliations

Affiliations

  • 1 West China School of Pharmacy Sichuan University, Chengdu, Sichuan 610041, China.
  • 2 Laboratory of Anesthesiology & Critical Care Medicine, Department of Anesthesiology, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, Sichuan University, Chengdu, Sichuan 610041, China.
  • 3 Department of Emergency, West China Hospital of Sichuan University, Chengdu, Sichuan 610041, China.
  • 4 West China School of Pharmacy Sichuan University, Chengdu, Sichuan 610041, China. Electronic address: [email protected].
PMID: 35091071 DOI: 10.1016/j.bmcl.2022.128587
Abstract

A series of novel procaine derivatives for intravenous anesthesia were prepared and evaluated by physicochemical properties and pharmacodynamic experiments in vivo and in vitro. Systematic optimization of procaine led to the identification of 6f, 6g, 6h, 6o, 6p and 6q with higher TI value and moderate log D. Compared with procaine (TI = 1.65), most procaine derivatives demonstrated better security, among whichcompound 6h (TI = 2.68)was the most notable one and showed fewer adverse events in Animals. The result of hNR2B-HEK293 assay indicated that compound 6h suppressed the NMDA receptor 2B subtype channel activity and it showed more than 80% inhibitory effect at the concentration of 500 μM.

Keywords

Continuous infusion; NMDA receptor; Procaine; Safety evaluation; Structure-activity relationship.

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