(1'R,5α,6R,7R,14α)-1'-phenyl-1'-(4,5-epoxy-7,8-dihydro-3,6-dimethoxy-7β-methyl-17-cyclopropylmethyl-6,14-ethanomorphinan-7-yl)-methan-1'-ol | 1417783-61-9

• 分子结构分类: 有机化合物 - 生物碱及其衍生物 - 吗啡烷
• 英文名称: (1'R,5α,6R,7R,14α)-1'-phenyl-1'-(4,5-epoxy-7,8-dihydro-3,6-dimethoxy-7β-methyl-17-cyclopropylmethyl-6,14-ethanomorphinan-7-yl)-methan-1'-ol
• 英文别名: (1′R,5α,6R,7R,14α)-1′-phenyl-1′-(4,5-epoxy-7,8-dihydro-3,6-dimethoxy-7β-methyl 17-cyclopropylmethyl-6,14-etheno-morphinan-7-yl)methan-1′-ol
• CAS: 1417783-61-9
• 化学式: C₃₂H₃₉NO₄
• 分子量: 501.666
• InChiKey: KWUYBPPEGTWYTB-XOSCKEEYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.04
• 重原子数：
  37.0
• 可旋转键数：
  6.0
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  51.16
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  盐酸 、 (1'R,5α,6R,7R,14α)-1'-phenyl-1'-(4,5-epoxy-7,8-dihydro-3,6-dimethoxy-7β-methyl-17-cyclopropylmethyl-6,14-ethanomorphinan-7-yl)-methan-1'-ol 在 六甲基磷酰三胺 、 1-丙烷硫醇钠 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以75 mg的产率得到(1'R,5α,6R,7R,14α)-1'-phenyl-1'-(4,5-epoxy-7,8-dihydro-3-hydroxy-6-methoxy-7β-methyl-17-cyclopropylmethyl-6,14-ethanomorphinan-7-yl)methan-1'-ol hydrochloride
  参考文献：
  名称：

  C7β-Methyl Analogues of the Orvinols: The Discovery of Kappa Opioid Antagonists with Nociceptin/Orphanin FQ Peptide (NOP) Receptor Partial Agonism and Low, or Zero, Efficacy at Mu Opioid Receptors

  摘要：

  Buprenorphine is a successful analgesic and treatment for opioid abuse, with both activities relying on its partial agonist activity at mu opioid receptors. However, there is substantial interest in its activities at the kappa opioid and nociceptin/orphanin FQ peptide receptors. This has led to an interest in developing compounds with a buprenorphine-like pharmacological profile but with lower efficacy at mu opioid receptors. The present article describes aryl ring analogues of buprenorphine in which the standard C20-methyl group has been moved to the C7 beta position, resulting in ligands with the desired profile. In particular, moving the methyl group has resulted in far more robust kappa opioid antagonist activity than seen in the standard orvinol series. Of the compounds synthesized, a number, including 15a, have a profile of interest for the development of drug abuse relapse prevention therapies or antidepressants and others (e.g., 8c), as analgesics with a reduced side-effect profile.

  DOI：

  10.1021/acs.jmedchem.5b00130
• 作为产物：
  描述：

  N-cyclopropylcarbonyl-6,14-endo-ethano-7β-methylnornepenthol 在 lithium aluminium tetrahydride 、 草酰氯 、 二甲基亚砜 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 25.33h， 生成 (1'R,5α,6R,7R,14α)-1'-phenyl-1'-(4,5-epoxy-7,8-dihydro-3,6-dimethoxy-7β-methyl-17-cyclopropylmethyl-6,14-ethanomorphinan-7-yl)-methan-1'-ol
  参考文献：
  名称：

  C7β-Methyl Analogues of the Orvinols: The Discovery of Kappa Opioid Antagonists with Nociceptin/Orphanin FQ Peptide (NOP) Receptor Partial Agonism and Low, or Zero, Efficacy at Mu Opioid Receptors

  摘要：

  Buprenorphine is a successful analgesic and treatment for opioid abuse, with both activities relying on its partial agonist activity at mu opioid receptors. However, there is substantial interest in its activities at the kappa opioid and nociceptin/orphanin FQ peptide receptors. This has led to an interest in developing compounds with a buprenorphine-like pharmacological profile but with lower efficacy at mu opioid receptors. The present article describes aryl ring analogues of buprenorphine in which the standard C20-methyl group has been moved to the C7 beta position, resulting in ligands with the desired profile. In particular, moving the methyl group has resulted in far more robust kappa opioid antagonist activity than seen in the standard orvinol series. Of the compounds synthesized, a number, including 15a, have a profile of interest for the development of drug abuse relapse prevention therapies or antidepressants and others (e.g., 8c), as analgesics with a reduced side-effect profile.

  DOI：

  10.1021/acs.jmedchem.5b00130