(4bR,6R,8aS,9R)-6-(azidomethyl)-11-(cyclopropylmethyl)-3-methoxy-5,6,7,8,9,10-hexahydro-9,4b-(epiminoethano)-6,8a-epoxyphenanthrene | 1103501-77-4

• 分子结构分类: 有机化合物 - 苯类化合物 - 菲及其衍生物
• 英文名称: (4bR,6R,8aS,9R)-6-(azidomethyl)-11-(cyclopropylmethyl)-3-methoxy-5,6,7,8,9,10-hexahydro-9,4b-(epiminoethano)-6,8a-epoxyphenanthrene
• CAS: 1103501-77-4
• 化学式: C₂₂H₂₈N₄O₂
• 分子量: 380.49
• InChiKey: OVCZQUYTJZPGGJ-GXRSIYKFSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.98
• 重原子数：
  28.0
• 可旋转键数：
  5.0
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.73
• 拓扑面积：
  70.46
• 氢给体数：
  0.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (4bR,6R,8aS,9R)-6-(azidomethyl)-11-(cyclopropylmethyl)-3-methoxy-5,6,7,8,9,10-hexahydro-9,4b-(epiminoethano)-6,8a-epoxyphenanthrene 在 吡啶 、 palladium 10% on activated carbon 、 camphor-10-sulfonic acid 、 氢气 、 sodium hydride 作用下， 以 四氢呋喃 、 甲醇 、 mineral oil 为溶剂， 反应 15.5h， 生成 N-[(17-cyclopropylmethyl-6β,14β-epoxy-3-methoxymorphinan-6α-yl)methyl]-N-methylbenzamide
  参考文献：
  名称：

  Synthesis of 6,14-epoxymorphinan derivatives and their pharmacologies

  摘要：

  A novel 6,14-epoxymorphinan benzamide derivative (NS22) that was previously reported showed opioid kappa receptor agonistic activity and analgesic activity. The unsatisfactory kappa selectivity of NS22 led us to synthesize its derivatives to improve the opioid kappa receptor selectivity and the agonist activity. In the course of SAR of the various derivatives, 17-benzyl-6,14-epoxymorphinan derivatives (KNT-33, 53, 55, 80, 90, 133) were found to show high selectivities and affinities for the opioid kappa receptor. In addition, KNT-33, 53, 55 showed dose-dependent analgesic effects in acetic acid writhing tests. Therefore, 17-benzyl substituents may play an important role for developing kappa selectivity. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2010.12.035
• 作为产物：
  描述：

  在 sodium azide 作用下， 以 二甲基亚砜 为溶剂， 生成 (4bR,6R,8aS,9R)-6-(azidomethyl)-11-(cyclopropylmethyl)-3-methoxy-5,6,7,8,9,10-hexahydro-9,4b-(epiminoethano)-6,8a-epoxyphenanthrene
  参考文献：
  名称：

  Synthesis of a novel 6,14-epoxymorphinan derivative and its pharmacology

  摘要：

  A novel 6,14-epoxymorphinan benzamide derivative (NS22) was synthesized, which showed opioid kappa receptor agonistic activity in the [(35)S]GTP gamma S binding assay. The antinociceptive effect of NS22 was evaluated in the tail-flick and the hot-plate test. This compound showed a potent antinociceptive activity in mice by sc administration, which was attenuated with nor-BNI (selective opioid kappa receptor antagonist). (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2008.10.081