(2E)-N-[(5R,6R)-17-(cyclopropylmethyl)-4,5-epoxy-3-hydroxymorphinan-6-yl]-3-(furan-3-yl)-N-methylprop-2-enamide | 152658-20-3

• 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: (2E)-N-[(5R,6R)-17-(cyclopropylmethyl)-4,5-epoxy-3-hydroxymorphinan-6-yl]-3-(furan-3-yl)-N-methylprop-2-enamide
• 英文别名: 17-cyclopropylmethyl-4,5α-epoxy-3-hydroxy-6β-[N-methyl-trans-3-(3-furyl)acrylamido]morphinan；(E)-N-[(4R,4aR,7R,7aR,12bS)-3-(cyclopropylmethyl)-9-hydroxy-2,4,4a,5,6,7,7a,13-octahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-yl]-3-(furan-3-yl)-N-methylprop-2-enamide
• CAS: 152658-20-3
• 化学式: C₂₈H₃₂N₂O₄
• 分子量: 460.573
• InChiKey: PXGJPRXHBFMPLD-RGFCBMLDSA-N

物化性质

• 沸点：
  668.1±55.0 °C(predicted)
• 密度：
  1.35±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  34
• 可旋转键数：
  5
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.54
• 拓扑面积：
  66.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  17-(cyclopropylmethyl)-4,5α-epoxy-6-oxo-morphinan 在 palladium on activated charcoal 、 氢气 、 对甲苯磺酸 、 三乙胺 、 苯甲酸 作用下， 以 甲醇 、 二氯甲烷 、 苯 为溶剂， 生成 (2E)-N-[(5R,6R)-17-(cyclopropylmethyl)-4,5-epoxy-3-hydroxymorphinan-6-yl]-3-(furan-3-yl)-N-methylprop-2-enamide
  参考文献：
  名称：

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

  摘要：

  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.

  DOI：

  10.1016/j.bmcl.2012.05.122

文献信息

• MORPHINAN DERIVATIVE AND MEDICINAL USE
  申请人：TORAY INDUSTRIES, INC.

  公开号：EP0577847A1

  公开（公告）日：1994-01-12

  A morphinan derivative represented by general formula (1) or a pharmacologically acceptable acid addition salt thereof, an analgesic and diuretic containing the same as the active ingredient, and a process for producing the same The invention compound has potent analgesic and diuretic activities as a highly selective κ-opioid agonist, thus being useful as an analgesic and diuretic.

  一种由通式（1）代表的吗啡南衍生物或其药理上可接受的酸加成盐，一种含有吗啡南衍生物作为活性成分的镇痛剂和利尿剂，以及生产吗啡南衍生物的工艺。 本发明化合物作为一种高选择性κ-阿片激动剂，具有强效的镇痛和利尿活性，因此可用作镇痛剂和利尿剂。
• ANTITUSSIVE
  申请人：TORAY INDUSTRIES, INC.

  公开号：EP0657163A1

  公开（公告）日：1995-06-14

  An antitussive containing a compound represented by general formula (I) or a salt thereof as the active ingredient, wherein symbol ... represents a double or single bond; R¹ represents alkyl, cycloalkylalkyl, cycloalkenylalkyl, aryl, aralkyl, alkenyl, allyl, furan-2-ylalkyl or thiophene-2-ylalkyl; R² represents hydrogen, hydroxy, nitro, alkanoyloxy, alkoxy, alkyl or -NR⁹R¹⁰, wherein R⁹ and R¹⁰ represents each hydrogen, etc.; R³ represents hydrogen, hydroxy, alkanoyloxy or alkoxy; A represents -XC(=Y)-, -XC(=Y)Z-, -X-, -XSO₂- or -OC(OR⁴)R⁴-, wherein X, Y and Z represent each independently NR⁴ (wherein R⁴ represents hydrogen, etc.), S or O; B represents a valence bond, alkylene, etc., acyclic unsaturated hydrocarbon, etc.; R⁵ represents hydrogen, benzene ring, etc.; R⁶ and R⁷ represent each hydrogen, etc., or are combined together to represent -O-, -CH₂-, -S-, etc.; and R⁸ represents hydrogen, alkyl or alkanoyl.

  一种含有通式(I)代表的化合物或其盐作为活性成分的止咳剂，其中符号...代表双键或单键；R¹代表烷基、环烷基烷基、环烯基烷基、芳基、芳烷基、烯基、烯丙基、呋喃-2-基烷基或噻吩-2-基烷基；R²代表氢、羟基、硝基、烷酰氧基、烷氧基、烷基或-NR⁹R¹⁰，其中 R⁹和 R¹⁰ 各自代表氢等。A 代表-XC(=Y)-、-XC(=Y)Z-、-X-、-XSO₂- 或-OC(OR⁴)R⁴-，其中 X、Y 和 Z 各自独立地代表 NR⁴（其中 R⁴ 代表氢等）、S 或 O；B 代表价键、亚烷基等、R⁵ 代表氢、苯环等；R⁶ 和 R⁷ 各自代表氢等，或组合在一起代表-O-、-CH₂-、-S-等；以及 R⁸ 代表氢、烷基或烷酰基。
• BRAIN CELL PROTECTIVE
  申请人：TORAY INDUSTRIES, INC.

  公开号：EP0661283A1

  公开（公告）日：1995-07-05

  A novel brain cell protective containing a morphinane derivative represented by the compound of formula (1) or a pharmacologically acceptable acid-addition salt thereof as the active ingredient. This compound exhibits an excellent protective effect against cranial nerve cell necrosis in both in vitro and in vivo pharmacological tests, and hence can be used for preventing or treating ischemic encephalopathy, cranial nerve cell disorder, and dementia.

  一种新型脑细胞保护剂，含有以式（1）化合物或其药理学上可接受的酸加成盐为代表的吗啡烷衍生物作为活性成分。该化合物在体外和体内药理试验中对颅神经细胞坏死均有很好的保护作用，因此可用于预防或治疗缺血性脑病、颅神经细胞紊乱和痴呆症。
• ANTIPRURITIC AGENT FOR PRURITUS CAUSED BY MULTIPLE SCLEROSIS
  申请人：TORAY INDUSTRIES, INC.

  公开号：EP1870413A1

  公开（公告）日：2007-12-26

  An antipruritic against pruritus caused by multiple sclerosis is disclosed. The antipruritic comprises as an effective ingredient an κ opioid receptor agonist compound having a 4,5-epoxymorphinan skeleton and having a specific chemical structure, such as Compound 1 having the following structure:

  本发明公开了一种抗多发性硬化症引起的瘙痒症的止痒剂。该止痒剂的有效成分包括一种具有 4,5-epoxymorphinan 骨架和特定化学结构的 κ 阿片受体激动剂化合物，例如具有以下结构的化合物 1：
• EP0657163B1
  申请人：——

  公开号：EP0657163B1

  公开（公告）日：1998-10-14