7(E)-(1-Naphthylmethylene)naltrexone | 167309-79-7

• 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(E)-(1-Naphthylmethylene)naltrexone
• 英文别名: 7(E)-(1-naphthylidene)naltrexone；(E)-7-(1-naphthylidene)naltrexone；(4R,4aS,6E,7aR,12bS)-3-(cyclopropylmethyl)-4a,9-dihydroxy-6-(naphthalen-1-ylmethylidene)-1,2,4,5,7a,13-hexahydro-4,12-methanobenzofuro[3,2-e]isoquinolin-7-one
• CAS: 167309-79-7
• 化学式: C₃₁H₂₉NO₄
• 分子量: 479.576
• InChiKey: LDINXOXSKGHJMD-MSSQLISWSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  36
• 可旋转键数：
  3
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.39
• 拓扑面积：
  70
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  7(E)-(1-Naphthylmethylene)naltrexone 以 二氯甲烷 为溶剂， 以68%的产率得到7(Z)-(1-Naphthylmethylene)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
• 作为产物：
  描述：

  盐酸纳曲酮 、 1-萘甲醛 在 sodium hydroxide 作用下， 反应 120.0h， 以26%的产率得到7(E)-(1-Naphthylmethylene)naltrexone
  参考文献：
  名称：

  7-Arylidenenaltrexones as Selective δ₁ Opioid Receptor Antagonists

  摘要：

  A series of 7-arylidinenaltrexones (2a-m) related to the prototypical delta(1)-selective antagonist, 7-benzylidenenaltrexone 1 (BNTX), have been synthesized in an effort to develop more selective ligands. Testing in smooth muscle preparations revealed that members of the series exhibited varying degrees of selectively for delta receptors, with the o-methoxy (2e) and o-chloro (2j) congeners being most potent and most selective (Ke similar to 0.8 nm). Evaluation of 1, 2e, and 2f sc in mice using the tail-flick procedure indicated that they are selective delta(1) opioid receptor antagonists in the lower dose range. At high doses these ligands, including BNTX, exhibited decreased delta(1) selectivity due to increases in the ED50 ratios of [D-Ser(2),Leu(5)]enkephalin-Thr(6) and morphine. It is concluded that 2e and 2f possess in vivo selectivity similar to that of BNTX, but are less potent as delta(1) antagonists.

  DOI：

  10.1021/jm980384s