2-benzoyl-1-cyano-6,7,8-trimethoxy-1,2-dihydroisoquinoline | 917086-55-6

• 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: 2-benzoyl-1-cyano-6,7,8-trimethoxy-1,2-dihydroisoquinoline
• 英文别名: 2-benzoyl-6,7,8-trimethoxy-1H-isoquinoline-1-carbonitrile
• CAS: 917086-55-6
• 化学式: C₂₀H₁₈N₂O₄
• 分子量: 350.374
• InChiKey: GNDKJXHKMIVNJC-UHFFFAOYSA-N

物化性质

• 熔点：
  155-157 °C(Solvent: Diethyl ether)
• 沸点：
  571.6±50.0 °C(Predicted)
• 密度：
  1.29±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.9
• 重原子数：
  26
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  71.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-benzoyl-1-cyano-6,7,8-trimethoxy-1,2-dihydroisoquinoline 在 sodium hydroxide 、 sodium tetrahydroborate 、 sodium hydride 作用下， 以 甲醇 、 乙醇 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 6.25h， 生成 6,7,8-trimethoxy-2-methyl-1-naphthalen-2-ylmethyl-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
• 作为产物：
  描述：

  2-benzoyl-1-cyano-6,7-dimethoxy-1,2-dihydroisoquinoline 、 6,7,8-Trimethoxyisoquinoline 生成 2-benzoyl-1-cyano-6,7,8-trimethoxy-1,2-dihydroisoquinoline
  参考文献：
  名称：

  BIS1,2,3,4-TETRAHYDROISOQUINOLINE DERIVATIVES AND THEIR USES AS PHARMACEUTICALS

  摘要：

  使用公式（I）所代表的双1,2,3,4-四氢异喹啉衍生物作为SK通道阻滞剂，并用于制备治疗中枢神经系统疾病的药物。

  公开号：

  US20090093517A1

文献信息

• Synthesis and Radioligand Binding Studies of Bis-isoquinolinium Derivatives as Small Conductance Ca²⁺-Activated K⁺ Channel Blockers
  作者：Amaury Graulich、Sébastien Dilly、Amaury Farce、Jacqueline Scuvée-Moreau、Olivier Waroux、Cédric Lamy、Philippe Chavatte、Vincent Seutin、Jean-François Liégeois

  DOI：10.1021/jm070412j

  日期：2007.10.1

  Starting from the scaffold of N-methyllaudanosine and N-methylnoscapine, which are known small conductance Ca2+-activated K+ channel blockers, original bis-isoquinolinium derivatives were synthezised and evaluated using binding studies, electrophysiology, and molecular modeling. These quaternary compounds are powerful blockers, and the most active ones have 10 times more affinity for the channels than dequalinium. The unsubstituted compounds possess a weaker affinity than the analogues having a 6,7-dimethoxy- or a 6,7,8-trimethoxy substitution. The length of the linker has no influence in the alkane derivatives. In relation to the xylene derivatives, the affinities are higher for the ortho and meta isomers. These results are well corroborated by a molecular modeling study. Finally, the most effective compounds have been tested in electrophysiological experiments on midbrain dopaminergic neurons and demonstrate the blocking potential of the apamin-sensitive after-hyperpolarization.