Design, Synthesis, and Activity Study of Water-Soluble, Rapid-Release Propofol Prodrugs
| Autor: | Chang-Cui Zhou, Rui Ling, Pei-Xi Hong, Yi Kang, Qing-Rong Qi, Xing-Hai Song, Liang-Quan Liu, Jun Yang |
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| Rok vydání: | 2020 |
| Předmět: |
Male
Duration time Amino Acids Cyclic Pharmacology Mice chemistry.chemical_compound Drug Discovery medicine Animals Prodrugs Propofol Glycolic acid Fospropofol Water Prodrug Glycolates Water soluble Solubility Design synthesis chemistry Drug Design Pharmacodynamics Molecular Medicine Anesthetics Intravenous medicine.drug |
| Zdroj: | Journal of Medicinal Chemistry. 63:7857-7866 |
| ISSN: | 1520-4804 0022-2623 |
| DOI: | 10.1021/acs.jmedchem.0c00698 |
| Popis: | 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 (3e, 3g, and 3j) 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. |
| Databáze: | OpenAIRE |
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