1-(3,4-dimethoxy-benzyl)-6,7,8-trimethoxy-2-methyl-1,2,3,4-tetrahydro-isoquinoline | 53392-67-9

• 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: 1-(3,4-dimethoxy-benzyl)-6,7,8-trimethoxy-2-methyl-1,2,3,4-tetrahydro-isoquinoline
• 英文别名: 1-<3,4-Dimethoxy-benzyl>-6,7,8-trimethoxy-N-methyl-1,2,3,4-tetrahydro-isochinolin；8-Methoxylaudanosin；1-[(3,4-dimethoxyphenyl)methyl]-6,7,8-trimethoxy-2-methyl-3,4-dihydro-1H-isoquinoline
• CAS: 53392-67-9
• 化学式: C₂₂H₂₉NO₅
• 分子量: 387.476
• InChiKey: LLALSPNIDWQWQM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  28
• 可旋转键数：
  7
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  49.4
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-(3,4-dimethoxy-benzyl)-6,7,8-trimethoxy-2-methyl-1,2,3,4-tetrahydro-isoquinoline 、 碘甲烷 以 乙腈 为溶剂， 反应 4.0h， 以88%的产率得到1-(3,4-dimethoxy-benzyl)-6,7,8-trimethoxy-2,2-dimethyl-1,2,3,4-tetrahydro-isoquinolinium; iodide
  参考文献：
  名称：

  Synthesis and Radioligand Binding Studies of Methoxylated 1,2,3,4-Tetrahydroisoquinolinium Derivatives as Ligands of the Apamin-Sensitive Ca²⁺-Activated K⁺ Channels

  摘要：

  Several methoxylated 1,2,3,4-tetrahydroisoquinoliniums derived from N-methyl-laudanosine and N-methyl-noscapine were synthesized and evaluated for their affinity for apamin-sensitive binding sites. The quaternary ammonium derivatives have a higher affinity with regard to the tertiary amines. 6,7-Dimethoxy analogues possess a higher affinity than the 6,8- and 7,8- dimethoxy isomers. A 3,4-dimethoxybenzyl or a 2-naphthylmethyl moiety in C-1 position are more favorable than a 3,4-dimethoxyphenethyl group. Smaller groups such as propyl or isobutyl are unfavorable. In 6,7-dimethoxy analogues, increasing the size and lipophilicity with a naphthyl group in the C-1 position leads to a slight increase of affinity, while the same group in the 6,7,8- trimethoxy series is less favorable. The 6,7,8- trimethoxy derivative 3f is the first tertiary amine in the series to possess an affinity close to that of N-methyl-laudanosine and N-methyl-noscapine. Moreover, electrophysiological studies show that the most effective compound 4f blocks the apamin-sensitive afterhyperpolarization in rat dopaminergic neurons.

  DOI：

  10.1021/jm0607395
• 作为产物：
  描述：

  (3,4-二甲氧基苯基)乙酰氯 在 磷酸酐 、 sodium tetrahydroborate 、 三乙胺 作用下， 以 甲醇 、 乙酸乙酯 、 甲苯 、 乙腈 为溶剂， 反应 3.75h， 生成 1-(3,4-dimethoxy-benzyl)-6,7,8-trimethoxy-2-methyl-1,2,3,4-tetrahydro-isoquinoline
  参考文献：
  名称：

  Synthesis and Radioligand Binding Studies of Methoxylated 1,2,3,4-Tetrahydroisoquinolinium Derivatives as Ligands of the Apamin-Sensitive Ca²⁺-Activated K⁺ Channels

  摘要：

  Several methoxylated 1,2,3,4-tetrahydroisoquinoliniums derived from N-methyl-laudanosine and N-methyl-noscapine were synthesized and evaluated for their affinity for apamin-sensitive binding sites. The quaternary ammonium derivatives have a higher affinity with regard to the tertiary amines. 6,7-Dimethoxy analogues possess a higher affinity than the 6,8- and 7,8- dimethoxy isomers. A 3,4-dimethoxybenzyl or a 2-naphthylmethyl moiety in C-1 position are more favorable than a 3,4-dimethoxyphenethyl group. Smaller groups such as propyl or isobutyl are unfavorable. In 6,7-dimethoxy analogues, increasing the size and lipophilicity with a naphthyl group in the C-1 position leads to a slight increase of affinity, while the same group in the 6,7,8- trimethoxy series is less favorable. The 6,7,8- trimethoxy derivative 3f is the first tertiary amine in the series to possess an affinity close to that of N-methyl-laudanosine and N-methyl-noscapine. Moreover, electrophysiological studies show that the most effective compound 4f blocks the apamin-sensitive afterhyperpolarization in rat dopaminergic neurons.

  DOI：

  10.1021/jm0607395

文献信息

• Synthesis and Radioligand Binding Studies of Methoxylated 1,2,3,4-Tetrahydroisoquinolinium Derivatives as Ligands of the Apamin-Sensitive Ca²⁺-Activated K⁺ Channels
  作者：Amaury Graulich、Jacqueline Scuvée-Moreau、Livia Alleva、Cédric Lamy、Olivier Waroux、Vincent Seutin、Jean-François Liégeois

  DOI：10.1021/jm0607395

  日期：2006.11.30

  Several methoxylated 1,2,3,4-tetrahydroisoquinoliniums derived from N-methyl-laudanosine and N-methyl-noscapine were synthesized and evaluated for their affinity for apamin-sensitive binding sites. The quaternary ammonium derivatives have a higher affinity with regard to the tertiary amines. 6,7-Dimethoxy analogues possess a higher affinity than the 6,8- and 7,8- dimethoxy isomers. A 3,4-dimethoxybenzyl or a 2-naphthylmethyl moiety in C-1 position are more favorable than a 3,4-dimethoxyphenethyl group. Smaller groups such as propyl or isobutyl are unfavorable. In 6,7-dimethoxy analogues, increasing the size and lipophilicity with a naphthyl group in the C-1 position leads to a slight increase of affinity, while the same group in the 6,7,8- trimethoxy series is less favorable. The 6,7,8- trimethoxy derivative 3f is the first tertiary amine in the series to possess an affinity close to that of N-methyl-laudanosine and N-methyl-noscapine. Moreover, electrophysiological studies show that the most effective compound 4f blocks the apamin-sensitive afterhyperpolarization in rat dopaminergic neurons.