17-(cyclopropylmethyl)-7α-benzyl-4,5α-epoxy-3,14-dihydromorphinan-6-one

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• 英文名称: 17-(cyclopropylmethyl)-7α-benzyl-4,5α-epoxy-3,14-dihydromorphinan-6-one
• 英文别名: 7α-benzylnaltrexone；(4R,4aS,6S,7aR,12bS)-6-benzyl-3-(cyclopropylmethyl)-4a,9-dihydroxy-2,4,5,6,7a,13-hexahydro-1H-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one
• 化学式: C₂₇H₂₉NO₄
• 分子量: 431.532
• InChiKey: ZLMLSUIQTYFLKF-XKVUGNILSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  32
• 可旋转键数：
  4
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  70
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  盐酸纳曲酮 在 palladium on activated charcoal sodium hydroxide 、 氢气 作用下， 以 甲醇 、 乙醇 为溶剂， -5.0 ℃ 、241.32 kPa 条件下， 反应 16.0h， 生成 17-(cyclopropylmethyl)-7α-benzyl-4,5α-epoxy-3,14-dihydromorphinan-6-one
  参考文献：
  名称：

  Synthesis of naltrexone-derived .delta.-opioid antagonists. Role of conformation of the .delta. address moiety

  摘要：

  Naltrindole (1) (NTI) is a highly potent and selective delta-opioid receptor antagonist. In an effort to understand the origin of the high potency, affinity, and selectivity of NTI, we have examined the conformational role of its indolic benzene moiety through the synthesis of related naltrexone derivatives 3-8, which contain the benzene moiety in different orientations and at different attachments in the molecule. One of these naltrexone derivatives, 5, whose 7-indanyl benzene moiety is orthogonal to ring C of the morphinan system, is a potent F-opioid receptor antagonist in vitro and in vivo. Computer-assisted molecular overlay studies of the minimized structures (2-8) revealed the importance of the position of the benzene moiety for effective interaction with delta-opioid receptors. In compounds 2, 4, and 5, the aromatic ring falls in the same region of space as that of the indolic benzene moiety of NTI, and all of these ligands possessed significant activity at delta-opioid receptors. Analogues (3 and 6-8) which were shown to have relatively weak delta-opioid receptor antagonist potency have their aromatic groups located in a space that is different from that of the more potent analogues.

  DOI：

  10.1021/jm00031a006

文献信息

• Antitrichomonal activity of δ opioid receptor antagonists, 7-benzylidenenaltrexone derivatives
  作者：Noriki Kutsumura、Yasuaki Koyama、Yasuyuki Nagumo、Ryo Nakajima、Yoshiyuki Miyata、Naoshi Yamamoto、Tsuyoshi Saitoh、Naoko Yoshida、Satoshi Iwata、Hiroshi Nagase

  DOI：10.1016/j.bmc.2017.06.026

  日期：2017.8

  The 7-benzylidenenaltrexone (BNTX) derivatives 2a–v, 3a–c, 13a–c, and 14a were synthesized from naltrexone (1) and evaluated for their antitrichomonal activity. The structure-activity-relationship studies found that 4-iodo-BNTX (2g) showed the highest activity (IC50 = 10.5 µM) and the affinity for the opioid receptor was less important for antitrichomonal activity against Trichomonas vaginalis. The

  从纳曲酮（1）合成了7-亚苄基纳曲酮（BNTX）衍生物2a–v，3a–c，13a–c和14a，并评估了其抗滴虫活性。结构-活性-关系研究发现，4-碘-BNTX（2g）表现出最高的活性（IC 50  = 10.5 µM），对阿片样物质受体的亲和力对阴道毛滴虫的抗滴虫活性的重要性较小。。带有迈克尔受体双键和酚羟基的吗啡喃骨架将是开发抗滴虫剂的特定模板。此外，BNTX衍生物的抗滴虫活性机制可能与标准药物甲硝唑不同。
• Investigation of 7-benzylidenenaltrexone derivatives as resistance reverser for chloroquine-resistant Plasmodium chabaudi
  作者：Yoshinori Miyata、Hideaki Fujii、Yuka Uenohara、Seiki Kobayashi、Tsutomu Takeuchi、Hiroshi Nagase

  DOI：10.1016/j.bmcl.2012.06.085

  日期：2012.8

  Derivatives of 7-benzylidenenaltrexone (BNTX), which was recently reported to be an effective chloroquine (CQ)-resistance reverser, were synthesized and evaluated for their CQ-resistance reversing activities. The synthesized derivatives showed CQ-resistance reversing effects. They also reacted with glutathione (GSH) both enzymatically and chemically, and inhibited glutathione reductase activity. 7-Benzyl derivative, which was obtained by reduction of the olefin group in alpha,beta-unsaturated ketone structure of BNTX, also exhibited CQ-resistance reversing effect, but its potency was significantly lower than that of BNTX. These outcomes suggested that the decrease in GSH level could be one of the mechanisms of CQ-resistance reversing effects induced by BNTX derivatives. (c) 2012 Elsevier Ltd. All rights reserved.
• Synthesis of naltrexone-derived .delta.-opioid antagonists. Role of conformation of the .delta. address moiety
  作者：P. S. Portoghese、M. Sultana、S. T. Moe、A. E. Takemori

  DOI：10.1021/jm00031a006

  日期：1994.3

  Naltrindole (1) (NTI) is a highly potent and selective delta-opioid receptor antagonist. In an effort to understand the origin of the high potency, affinity, and selectivity of NTI, we have examined the conformational role of its indolic benzene moiety through the synthesis of related naltrexone derivatives 3-8, which contain the benzene moiety in different orientations and at different attachments in the molecule. One of these naltrexone derivatives, 5, whose 7-indanyl benzene moiety is orthogonal to ring C of the morphinan system, is a potent F-opioid receptor antagonist in vitro and in vivo. Computer-assisted molecular overlay studies of the minimized structures (2-8) revealed the importance of the position of the benzene moiety for effective interaction with delta-opioid receptors. In compounds 2, 4, and 5, the aromatic ring falls in the same region of space as that of the indolic benzene moiety of NTI, and all of these ligands possessed significant activity at delta-opioid receptors. Analogues (3 and 6-8) which were shown to have relatively weak delta-opioid receptor antagonist potency have their aromatic groups located in a space that is different from that of the more potent analogues.