设计、合成及水溶性、快速释放型丙泊酚前药的活性研究。
Design, Synthesis, and Activity Study of Water-Soluble, Rapid-Release Propofol Prodrugs.
机构信息
Laboratory of Anesthesia and Critical Care Medicine, Translational Neuroscience Center, Department of Anesthesiology, Sichuan University West China Hospital, Sichuan University, Chengdu 610041, China.
Key Laboratory of Drug-Targeting and Drug Delivery System of the Education Ministry, Sichuan Engineering Laboratory for Plant-Sourced Drug and Sichuan Research Center for Drug Industrial Technology, Sichuan Research Center of Precision Engineering Technology for Small Molecule Drugs, West China School of Pharmacy Sichuan University, Chengdu 610041, China.
出版信息
J Med Chem. 2020 Jul 23;63(14):7857-7866. doi: 10.1021/acs.jmedchem.0c00698. Epub 2020 Jul 6.
In this work, a series of water-soluble propofol prodrugs were synthesized, and their propofol release rate and pharmacodynamic characteristics were measured. We found that inserting glycolic acid as a linker between propofol and the cyclic amino acid accelerated the release of propofol from prodrugs into the plasma while preserving its safety. In animal experiments, prodrugs (, , and ) were significantly better than fospropofol (the only water-soluble propofol prodrug that has been used clinically) in terms of safety, onset, and duration time of anesthesia. Their molar dose, onset time, and anesthesia duration time were comparable to those of propofol, helping to maintain the clinical benefits of propofol. The experimental results showed the potential of such compounds as water-soluble prodrugs of propofol.
在这项工作中，我们合成了一系列水溶性丙泊酚前药，并测量了它们的丙泊酚释放率和药效学特征。我们发现，将丙泊酚和环状氨基酸之间的乙二醇酸作为连接子插入，可以加速丙泊酚从前药向血浆中的释放，同时保持其安全性。在动物实验中，前药（ 、 、 ）在安全性、起效时间和麻醉持续时间方面明显优于已临床应用的唯一水溶性丙泊酚前药福泊酚。它们的摩尔剂量、起效时间和麻醉持续时间与丙泊酚相当，有助于保持丙泊酚的临床优势。实验结果表明，这些化合物有作为水溶性丙泊酚前药的潜力。
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