1,1'-(o-xylene-α,α'-diyl)-bisisoquinoline | 67258-31-5

• 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: 1,1'-(o-xylene-α,α'-diyl)-bisisoquinoline
• 英文别名: 1,1'-o-phenylenedimethyl-bis-isoquinoline；o-bis[(1-isoquinolyl)methyl]-benzene；1-[[2-(Isoquinolin-1-ylmethyl)phenyl]methyl]isoquinoline
• CAS: 67258-31-5
• 化学式: C₂₆H₂₀N₂
• 分子量: 360.458
• InChiKey: OZOOTBDENNMRRV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  6.2
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.08
• 拓扑面积：
  25.8
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1,1'-(o-xylene-α,α'-diyl)-bisisoquinoline 、 碘甲烷 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以84%的产率得到1,1'-(o-xylene-α,α'-diyl)-bis(2-methylisoquinolinium) diiodide
  参考文献：
  名称：

  Synthesis and Radioligand Binding Studies of Bis-isoquinolinium Derivatives as Small Conductance Ca²⁺-Activated K⁺ Channel Blockers

  摘要：

  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.

  DOI：

  10.1021/jm070412j
• 作为产物：
  描述：

  在 sodium hydroxide 作用下， 以 乙醇 为溶剂， 生成 1,1'-(o-xylene-α,α'-diyl)-bisisoquinoline
  参考文献：
  名称：

  Synthesis and Radioligand Binding Studies of Bis-isoquinolinium Derivatives as Small Conductance Ca²⁺-Activated K⁺ Channel Blockers

  摘要：

  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.

  DOI：

  10.1021/jm070412j