7(Z)-(9-Anthrylmethylene)naltrexone

• 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)-(9-Anthrylmethylene)naltrexone
• 英文别名: 17-(cyclopropylmethyl)-4,5-α-epoxy-7(Z)-(9-anthracylidene)-3,14-dihydroxymorphinan；(4R,4aS,6Z,7aR,12bS)-6-(anthracen-9-ylmethylidene)-3-(cyclopropylmethyl)-4a,9-dihydroxy-1,2,4,5,7a,13-hexahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one
• 化学式: C₃₅H₃₁NO₄
• 分子量: 529.635
• InChiKey: VOALNYMYZLUFTA-INBXWQOGSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.5
• 重原子数：
  40
• 可旋转键数：
  3
• 环数：
  9.0
• sp3杂化的碳原子比例：
  0.34
• 拓扑面积：
  70
• 氢给体数：
  2
• 氢受体数：
  5

上下游信息

• 上游原料

  中文名称	英文名称	CAS号	化学式	分子量
  纳曲酮	Naltrexone	16590-41-3	C20H23NO4	341.407

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)-(9-Anthrylmethylene)naltrexone
  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

• (<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.