(4aR,9aR)-6-methoxy-1,2-dihydro-9H-4a,9a-(ethanoiminomethano)fluoren-3(4H)-one | 1147799-39-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 茚满类
• 英文名称: (4aR,9aR)-6-methoxy-1,2-dihydro-9H-4a,9a-(ethanoiminomethano)fluoren-3(4H)-one
• CAS: 1147799-39-0
• 化学式: C₁₇H₂₁NO₂
• 分子量: 271.359
• InChiKey: IXWMIJNZFAHCOM-DLBZAZTESA-N

物化性质

• 沸点：
  449.1±45.0 °C(predicted)
• 密度：
  1.20±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.22
• 重原子数：
  20.0
• 可旋转键数：
  1.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.59
• 拓扑面积：
  38.33
• 氢给体数：
  1.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  (4aR,9aR)-6-methoxy-1,2-dihydro-9H-4a,9a-(ethanoiminomethano)fluoren-3(4H)-one 在 4-二甲氨基吡啶 、 甲烷磺酸 、 盐酸-N-乙基-Nˊ-(3-二甲氨基丙基)碳二亚胺 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 生成 C₃₀H₃₀N₂O₄
  参考文献：
  名称：

  Design and synthesis of quinolinopropellane derivatives with selective δ opioid receptor agonism

  摘要：

  Indolopropellane 2 was reported to show almost no binding affinity to the delta opioid receptor (DOR) in spite of the fact that 2 has both the propellane fundamental skeleton (message part) with binding ability to the opioid receptors and a possible DOR address structure (indole moiety). We developed the working hypothesis that almost no binding affinity of 2 to the DOR would be derived from its possibly stable bent conformer. To enable the propellane skeleton to adopt an extended conformation which would reasonably interact with the DOR, quinolinopropellanes 3a-d were designed which had an additional pharmacophore, quinoline nitrogen. The calculated binding free energies of ligand-DOR complexes strongly supported our working hypothesis. The synthesized quinolinopropellane 3a was a selective DOR full agonist, confirming our working hypothesis and the results of in silico investigation. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.04.098
• 作为产物：
  描述：

  在 溶剂黄146 、 锌 作用下， 生成 (4aR,9aR)-6-methoxy-1,2-dihydro-9H-4a,9a-(ethanoiminomethano)fluoren-3(4H)-one
  参考文献：
  名称：

  Design and synthesis of quinolinopropellane derivatives with selective δ opioid receptor agonism

  摘要：

  Indolopropellane 2 was reported to show almost no binding affinity to the delta opioid receptor (DOR) in spite of the fact that 2 has both the propellane fundamental skeleton (message part) with binding ability to the opioid receptors and a possible DOR address structure (indole moiety). We developed the working hypothesis that almost no binding affinity of 2 to the DOR would be derived from its possibly stable bent conformer. To enable the propellane skeleton to adopt an extended conformation which would reasonably interact with the DOR, quinolinopropellanes 3a-d were designed which had an additional pharmacophore, quinoline nitrogen. The calculated binding free energies of ligand-DOR complexes strongly supported our working hypothesis. The synthesized quinolinopropellane 3a was a selective DOR full agonist, confirming our working hypothesis and the results of in silico investigation. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2014.04.098

文献信息

• Synthesis and opioid receptor activity of indolopropellanes
  作者：Fuying Li、Linghuan Gaob、Chenlei Yin、Jie Chen、Jinggen Liu、Xin Xie、Ao Zhang

  DOI：10.1016/j.bmcl.2009.06.093

  日期：2009.8

  displayed moderate binding affinity and selectivity at the μ receptor, with compound 7b showing the highest affinity at this receptor with a Ki value of 40 nM, and 6- and 25-fold selectivity against δ and κ receptors, respectively. Function assays showed that indolopropellanes 7b and 7c possessed full agonistic activity at all the opioid receptors indicating a different interaction model existed.

  通过3-甲氧基-N-甲基-14-羟基吗啡喃-6-one 12的N-去甲基化，然后进行N-重烷基化，还原和Fischer吲哚环化，获得了一系列骨架重排的吲哚吗啡喃7a-d。通过X射线分析证实了该新型骨架的结构。这些新的吲哚在μ受体上表现出中等的结合亲和力和选择性，化合物7b在该受体上显示出最高亲和力，其K i值为40 nM，对δ和κ受体的选择性分别为6倍和25倍。功能测定表明吲哚丙二酮7b和7c 在所有阿片样物质受体上都具有完全激动作用，表明存在不同的相互作用模型。