Essential structure of opioid ¦Ê receptor agonist nalfurafine for binding to the ¦Ê receptor 2: Synthesis of decahydro(iminoethano)phenanthrene derivatives and their pharmacologies

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• 作者：Hiroshi Nagase ; Satomi Imaide ; Shigeto Hirayama ; Toru Nemoto ; Hideaki Fujii
• 关键词：Opioid ; ¦Ê Receptor ; Decahydro(iminoethano)phenanthrene ; Nalfurafine
• 刊名：Bioorganic and Medicinal Chemistry Letters
• 出版年：2012
• 出版时间：1 August, 2012
• 年：2012
• 卷：22
• 期：15
• 页码：5071-5074
• 全文大小：682 K

文摘

To clarify the essential structures of an opioid ¦Ê receptor selective agonist, nalfurafine, for binding to the ¦Ê receptor, we designed and synthesized some nalfurafine derivatives and the decahydro(iminoethano)phenanthrene derivatives with a cyclohexene moiety as a surrogate for the phenol ring. In addition to the 6-amide side chain and the 17-nitrogen substituted by a cyclopropylmethyl group, the 4,5-epoxy ring, phenolic hydroxy group, and angular hydroxy group played important roles in eliciting the binding properties of nalfurafine but these three moieties were not indispensable for binding to the ¦Ê receptor. Moreover, the phenol ring was also not essential for the binding to the ¦Ê receptor, and the cyclohexene moiety would play an important role in fixing the conformation of decahydro(iminoethano)phenanthrene derivatives to effectively raise the amide side chain, rendering a conformation that resembled the active one of nalfurafine.