7(Z)-Benzylidenenaltrexone | 129468-28-6

• 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: 7(Z)-Benzylidenenaltrexone
• 英文别名: 7-Benzylidenenaltrexone；(Z)-7-benzylidenenaltrexone；Morphinan-6-one, 17-(cyclopropylmethyl)-4,5-epoxy-3,14-dihydroxy-7-(phenylmethylene)-, (5alpha)-；(4R,4aS,6Z,7aR,12bS)-6-benzylidene-3-(cyclopropylmethyl)-4a,9-dihydroxy-1,2,4,5,7a,13-hexahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one
• CAS: 129468-28-6
• 化学式: C₂₇H₂₇NO₄
• 分子量: 429.516
• InChiKey: WXOUFNFMPVMGFZ-XEGDMQTMSA-N

物化性质

• 沸点：
  661.2±55.0 °C(Predicted)
• 密度：
  1.43±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  32
• 可旋转键数：
  3
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.44
• 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：

  纳曲酮 在 氢氧化钾 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 生成 7(Z)-Benzylidenenaltrexone
  参考文献：
  名称：

  (E)- and (Z)-7-Arylidenenaltrexones:  Synthesis and Opioid Receptor Radioligand Displacement Assays

  摘要：

  The E-isomer of 7-benzylidenenaltrexone (BNTX, la) was reported by Portoghese(1,2) as a highly selective delta-opioid antagonist. The corresponding Z-isomer Ib was not readily available through direct aldol condensation of naltrexone (6) with benzaldehyde, Using the photochemical methods employed by Lewis to isomerize cinnamamides,(3) we have obtained Z-isomer Ib in good yield from E-isomer la. A series of (E)- and (Z)-7-arylidenenaltrexone derivatives was prepared to study the effect of larger arylidene groups on opioid receptor affinity in this series. By aldol condensation of naltrexone (6) with benzaldehyde, 1-naphthaldehyde, 2-naphthaldehyde, 4-phenylbenzaldehyde, and 9-anthracaldehyde, the (E)-arylidenes were readily obtained. Photochemical isomerization afforded the corresponding Z-isomers. These compounds were evaluated via opioid receptor radioligand displacement assays. In these assays, the Z-isomers generally had higher affinity and were more delta-selective than the corresponding E-isomers. The (Z)-7-(1-naphthylidene)naltrexone (3b) showed the greatest selectivity (delta:mu ratio of 15) and highest affinity delta-binding (K-i = 0.7 nM). PM3 semiempirical geometry optimizations suggest a significant role for the orientation of the arylidene substituent in the binding affinity and delta-receptor selectivity. This work demonstrates that larger groups may be incorporated into the arylidene portion of the molecule with opioid receptor affinity being retained.

  DOI：

  10.1021/jm960573f

文献信息

• 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.
• US8569481B2
  申请人：——

  公开号：US8569481B2

  公开（公告）日：2013-10-29
• US9034798B2
  申请人：——

  公开号：US9034798B2

  公开（公告）日：2015-05-19
• (<i>E</i>)- and (<i>Z</i>)-7-Arylidenenaltrexones:  Synthesis and Opioid Receptor Radioligand Displacement Assays
  作者：Robert B. Palmer、Alana L. Upthagrove、Wendel L. Nelson

  DOI：10.1021/jm960573f

  日期：1997.2.1

  The E-isomer of 7-benzylidenenaltrexone (BNTX, la) was reported by Portoghese(1,2) as a highly selective delta-opioid antagonist. The corresponding Z-isomer Ib was not readily available through direct aldol condensation of naltrexone (6) with benzaldehyde, Using the photochemical methods employed by Lewis to isomerize cinnamamides,(3) we have obtained Z-isomer Ib in good yield from E-isomer la. A series of (E)- and (Z)-7-arylidenenaltrexone derivatives was prepared to study the effect of larger arylidene groups on opioid receptor affinity in this series. By aldol condensation of naltrexone (6) with benzaldehyde, 1-naphthaldehyde, 2-naphthaldehyde, 4-phenylbenzaldehyde, and 9-anthracaldehyde, the (E)-arylidenes were readily obtained. Photochemical isomerization afforded the corresponding Z-isomers. These compounds were evaluated via opioid receptor radioligand displacement assays. In these assays, the Z-isomers generally had higher affinity and were more delta-selective than the corresponding E-isomers. The (Z)-7-(1-naphthylidene)naltrexone (3b) showed the greatest selectivity (delta:mu ratio of 15) and highest affinity delta-binding (K-i = 0.7 nM). PM3 semiempirical geometry optimizations suggest a significant role for the orientation of the arylidene substituent in the binding affinity and delta-receptor selectivity. This work demonstrates that larger groups may be incorporated into the arylidene portion of the molecule with opioid receptor affinity being retained.