Novel Propofol Analogs: Design, Synthesis and Evaluation of Dihydrobenzofuran Derivatives as General Anesthetics
Jun-Jie Shi, Jia-Quan Feng, Yuan-Hai Zou, Yan Huo, Shi-Han Ma, Xiao-Jing He, Ze-Hong Wan, Xiang-Qing Xu, Zhi-Jing Hu, Yi-Long Shi, Jin-Hui Wu, Xiang-Yang Xu
TL;DR
Researchers designed new propofol analogs with better anesthetic effects and fewer side effects, showing promise for clinical use.
Contribution
A novel dihydrobenzofuran derivative, 53A, was developed with higher potency and safety compared to propofol.
Findings
Compound 53A showed higher potency and a wider safety margin than propofol in mice and rats.
Phosphate prodrug 56A outperformed fospropofol in efficiency and safety with faster recovery times.
Respiratory depression side effects were reduced in the new analogs.
Abstract
Background: Propofol is used worldwide as a short-acting intravenous anesthetic in clinical practice; however, side effects such as injection pain and respiratory depression remain clinically relevant. Therefore, identification of safer propofol analogs is required. Method: In response to the urgent need for optimized potency and reduced side effects, a series of dihydrobenzofuran derivatives were designed as expectedly better propofol analogs through conformational restriction. A loss of righting reflex assay was conducted to evaluate the sedative/anesthetic properties of the synthesized compounds, and a respiratory depression test was performed for safety assessment. Results: Most of the designed compounds were shown to possess promising anesthetic properties as propofol analogs. The represented 53A had higher potency and a wider safety margin (ED50:3.898 vs. 8.040 mg/kg in mice;…
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Taxonomy
TopicsAnesthesia and Sedative Agents · Pharmacological Receptor Mechanisms and Effects · Cancer, Stress, Anesthesia, and Immune Response