p-(4-Azipentyl)propofol: A Potent Photoreactive General Anesthetic Derivative of Propofol

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• 作者：Deirdre S. Stewart ; Pavel Y. Savechenkov ; Zuzana Dostalova ; David C. Chiara ; Rile Ge ; Douglas E. Raines ; Jonathan B. Cohen ; Stuart A. Forman ; Karol S. Bruzik ; Keith W. Miller
• 刊名：Journal of Medicinal Chemistry
• 出版年：2011
• 出版时间：December 8, 2011
• 年：2011
• 卷：54
• 期：23
• 页码：8124-8135
• 全文大小：426K
• 年卷期：v.54,no.23(December 8, 2011)
• ISSN：1520-4804

文摘

We synthesized 2,6-diisopropyl-4-[3-(3-methyl-3H-diazirin-3-yl)propyl]phenol (p-(4-azipentyl)propofol), or p-4-AziC5-Pro, a novel photoactivable derivative of the general anesthetic propofol. p-4-AziC5-Pro has an anesthetic potency similar to that of propofol. Like propofol, the compound potentiates inhibitory GABA<sub>Asub> receptor current responses and allosterically modulates binding to both agonist and benzodiazepine sites, assayed on heterologously expressed GABA<sub>Asub> receptors. p-4-AziC5-Pro inhibits excitatory current responses of nACh receptors expressed in Xenopus oocytes and photoincorporates into native nACh receptor-enriched Torpedo membranes. Thus, p-4-AziC5-Pro is a functional general anesthetic that both modulates and photoincorporates into Cys-loop ligand-gated ion channels, making it an excellent candidate for use in identifying propofol binding sites.