17-(2-phenylethyl)-6,7-dehydro-4,5α-epoxy-3,14-dihydroxy-6,7-2',3'-indolomorphinan

• 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: 17-(2-phenylethyl)-6,7-dehydro-4,5α-epoxy-3,14-dihydroxy-6,7-2',3'-indolomorphinan
• 英文别名: SYK-707；(1S,2S,13R,21R)-22-(2-phenylethyl)-14-oxa-11,22-diazaheptacyclo[13.9.1.01,13.02,21.04,12.05,10.019,25]pentacosa-4(12),5,7,9,15,17,19(25)-heptaene-2,16-diol
• 化学式: C₃₀H₂₈N₂O₃
• 分子量: 464.564
• InChiKey: FZLPZVPOKOYQGI-QVDUQQMDSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  35
• 可旋转键数：
  3
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  68.7
• 氢给体数：
  3
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  14-羟基二氢降吗啡酮盐酸盐 在 盐酸 、 3 A molecular sieve 、 MeOH buffer 、 potassium acetate 、 sodium cyanoborohydride 、 溶剂黄146 作用下， 反应 32.0h， 生成 17-(2-phenylethyl)-6,7-dehydro-4,5α-epoxy-3,14-dihydroxy-6,7-2',3'-indolomorphinan
  参考文献：
  名称：

  Opioid agonist and antagonist activities of morphindoles related to naltrindole

  摘要：

  A series of naltrindole-related ligands (4-10) with an N-methyl, N-phenethyl, N-cinnamyl, or an unsubstituted basic nitrogen were synthesized and tested for opioid agonist and antagonist activity in smooth muscle preparations and in mice. The nor compounds (4 and 6) and the phenethyl derivatives (5 and 8) displayed full agonist activity (IC50 = 85-179 nM) in the mouse vas deferens preparation (MVD) while the other members of the series exhibited partial agonist or weak antagonist activity. In the guinea pig ileum preparation (GPI), all compounds except 8 were partial agonists. The ligands that were evaluated in mice were found to produce antinociception that was not selectively mediated via delta opioid receptors. However, two of these ligands (4 and 5) appeared to be delta-selective opioid receptor antagonists at subthreshold doses for antinociception. The finding that all of the compounds bind selectively to delta opioid receptors in guinea pig brain membranes together with the in vitro pharmacology and in vivo antagonist studies suggests that the lack of delta agonist selectivity in vivo may be due to a number of factors, including a basic difference between the delta receptor system in the MVD and in the mouse brain. Further, it is suggested that the constellation of message and address components in the morphindole nucleus may tend to stabilize delta receptors in the brain in an antagonist state.

  DOI：

  10.1021/jm00101a009

文献信息

• Opioid agonist and antagonist activities of morphindoles related to naltrindole
  作者：P. S. Portoghese、D. L. Larson、M. Sultana、A. E. Takemori

  DOI：10.1021/jm00101a009

  日期：1992.11

  A series of naltrindole-related ligands (4-10) with an N-methyl, N-phenethyl, N-cinnamyl, or an unsubstituted basic nitrogen were synthesized and tested for opioid agonist and antagonist activity in smooth muscle preparations and in mice. The nor compounds (4 and 6) and the phenethyl derivatives (5 and 8) displayed full agonist activity (IC50 = 85-179 nM) in the mouse vas deferens preparation (MVD) while the other members of the series exhibited partial agonist or weak antagonist activity. In the guinea pig ileum preparation (GPI), all compounds except 8 were partial agonists. The ligands that were evaluated in mice were found to produce antinociception that was not selectively mediated via delta opioid receptors. However, two of these ligands (4 and 5) appeared to be delta-selective opioid receptor antagonists at subthreshold doses for antinociception. The finding that all of the compounds bind selectively to delta opioid receptors in guinea pig brain membranes together with the in vitro pharmacology and in vivo antagonist studies suggests that the lack of delta agonist selectivity in vivo may be due to a number of factors, including a basic difference between the delta receptor system in the MVD and in the mouse brain. Further, it is suggested that the constellation of message and address components in the morphindole nucleus may tend to stabilize delta receptors in the brain in an antagonist state.