17-(cyclopropylmethyl)-4,5α-epoxy-6-oxo-morphinan | 16590-46-8

• 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-(cyclopropylmethyl)-4,5α-epoxy-6-oxo-morphinan
• 英文别名: N-(cyclopropylmethyl)nordihydromorphinone；14-deoxynaltrexone；17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-morphinan-6-one；N-Cyclopropylmethyl-dihydronormorphinon；17-Cyclopropylmethyl-4,5alpha-epoxy-3-hydroxy-morphinan-6-one；(4R,4aR,7aR,12bS)-3-(cyclopropylmethyl)-9-hydroxy-1,2,4,4a,5,6,7a,13-octahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one
• CAS: 16590-46-8
• 化学式: C₂₀H₂₃NO₃
• 分子量: 325.408
• InChiKey: XNXORWDKIQPSNX-ILWKUFEGSA-N

物化性质

• 沸点：
  518.5±50.0 °C(Predicted)
• 密度：
  1.39±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.65
• 拓扑面积：
  49.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  17-(cyclopropylmethyl)-4,5α-epoxy-6-oxo-morphinan 在 间氯过氧苯甲酸 作用下， 以 二氯甲烷 为溶剂， 反应 1.0h， 以52%的产率得到(S)-17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-morphinan-6-one N-oxide
  参考文献：
  名称：

  [EN] N-OXIDES OF 4,5-EPOXY-MORPHINANIUM ANALOGS
  [FR] N-OXYDES D'ANALOGUES 4,5-ÉPOXY-MORPHINANIUM

  摘要：

  揭示了4,5-环氧吗啡啉盐类的新型N-氧化物。还揭示了含有4,5-环氧吗啡啉盐类的N-氧化物的药物组合物，以及它们的药用方法。所揭示的化合物可用作阿片受体调节剂等用途。

  公开号：

  WO2009067275A1
• 作为产物：
  描述：

  纳曲酮 在 platinum(IV) oxide 盐酸 、 氯化亚砜 、 camphor-10-sulfonic acid 、 氢气 、 三溴化硼 、 potassium carbonate 作用下， 以 吡啶 、 甲醇 、 二氯甲烷 、 甲苯 为溶剂， 反应 6.0h， 生成 17-(cyclopropylmethyl)-4,5α-epoxy-6-oxo-morphinan
  参考文献：
  名称：

  Osa, Yumiko; Ida, Yoshihiro; Yano, Yumiko, Heterocycles, 2006, vol. 69, # 1, p. 271 - 282

  摘要：

  DOI：

文献信息

• N-Oxides of 4,5-Epoxy-Morphinanium Analogs
  申请人：Perez Julio

  公开号：US20080234306A1

  公开（公告）日：2008-09-25

  Novel N-oxides of 4,5-epoxy-morphinanium analogs are disclosed. Pharmaceutical compositions containing the N-oxides of 4,5-epoxy-morphinanium analogs and methods of their pharmaceutical uses are also disclosed. The compounds disclosed are useful, inter alia, as modulators of opioid receptors.

  本发明公开了4,5-环氧-吗啡铵类似物的新型N-氧化物。本发明还公开了含有4,5-环氧-吗啡铵类似物的N-氧化物的制药组合物及其制药用途的方法。公开的化合物可用作阿片受体调节剂等用途。
• Synthesis of dihydromorphinones from dihydrocodeinones
  作者：V. N. Kalinin、N. I. Kobel'kova、D. E. Bodrov

  DOI：10.1007/bf00957463

  日期：1988.2
• Some Potent Morphine Antagonists Possessing High Analgesic Activity¹
  作者：Marshall Gates、Thomas A. Montzka

  DOI：10.1021/jm00332a002

  日期：1964.3
• Essential structure of opioid κ receptor agonist nalfurafine for binding to the κ receptor 2: Synthesis of decahydro(iminoethano)phenanthrene derivatives and their pharmacologies
  作者：Hiroshi Nagase、Satomi Imaide、Shigeto Hirayama、Toru Nemoto、Hideaki Fujii

  DOI：10.1016/j.bmcl.2012.05.122

  日期：2012.8

  To clarify the essential structures of an opioid kappa receptor selective agonist, nalfurafine, for binding to the kappa 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 kappa receptor. Moreover, the phenol ring was also not essential for the binding to the kappa 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. (C) 2012 Elsevier Ltd. All rights reserved.
• Nonequilibrium opioid antagonist activity of 6,14-dideoxynaltrexone derivatives
  作者：J. W. Schoenecker、A. E. Takemori、P. S. Portoghese

  DOI：10.1021/jm00389a014

  日期：1987.6

  A series of 6,14-dideoxynaltrexones that contain different electrophiles in the 6-position were synthesized and evaluated for nonequilibrium opioid antagonist activity in the guinea pig ileum and mouse vas deferens preparations. Members 3-5 of the series possessed irreversible antagonist activity profiles similar to those previously reported for the 14-hydroxy analogues. In contrast, the 14-deoxy-beta-funaltrexamine (14-deoxy-beta-FNA) analogue (6) exhibited a profile of irreversible antagonist activity that differed from that of beta-FNA. It was concluded that the 14-hydroxy group is not essential for irreversible blockage when the electrophile is capable of reacting with a broad spectrum of nucleophiles. However, with a highly selective electrophile such as the fumarate group, the 14-hydroxy function appears to play a role in aligning the molecule to optimize attack by a receptor-based nucleophile.