3-{[6-(5,8,9,13b-tetrahydro-6H-isoquino[1,2-a]isoquinolin-3-yloxy)hexyl]oxy}-5,8,9,13b-tetrahydro-6H-isoquino[1,2-a]isoquinoline | 1229321-27-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 四氢异喹啉
• 英文名称: 3-{[6-(5,8,9,13b-tetrahydro-6H-isoquino[1,2-a]isoquinolin-3-yloxy)hexyl]oxy}-5,8,9,13b-tetrahydro-6H-isoquino[1,2-a]isoquinoline
• 英文别名: 3-[6-(6,8,9,13b-tetrahydro-5H-isoquinolino[1,2-a]isoquinolin-3-yloxy)hexoxy]-6,8,9,13b-tetrahydro-5H-isoquinolino[1,2-a]isoquinoline
• CAS: 1229321-27-0
• 化学式: C₄₀H₄₄N₂O₂
• 分子量: 584.802
• InChiKey: WLXOCNXXBZJGFO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  8.2
• 重原子数：
  44
• 可旋转键数：
  9
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.4
• 拓扑面积：
  24.9
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  3-{[6-(5,8,9,13b-tetrahydro-6H-isoquino[1,2-a]isoquinolin-3-yloxy)hexyl]oxy}-5,8,9,13b-tetrahydro-6H-isoquino[1,2-a]isoquinoline 、 碘甲烷 以 甲醇 、 乙腈 为溶剂， 反应 6.0h， 以98%的产率得到7-methyl-3-({6-[(7-methyl-5,8,9,13b-tetrahydro-6H-isoquino[1,2-a]isoquinolinium-3-yl)oxy]hexyl}oxy)-5,8,9,13b-tetrahydro-6H-isoquino[1,2-a]isoquinolinium diiodide
  参考文献：
  名称：

  Bivalent 5,8,9,13b-tetrahydro-6H-isoquino[1,2-a]isoquinolines and -isoquinolinium salts: Novel heterocyclic templates for butyrylcholinesterase inhibitors

  摘要：

  Three different types of homobivalent compounds, 5,8,9,13b-tetrahydro-6H-isoqino[1,2-a]isoquinolines bearing tertiary N-atoms, their quaternary ammonium salts and their dibenzazecine analogues, connected by alkylene spacers of various lengths were synthesized. Compared to the therapeutically used inhibitor galanthamine, some of the bivalent compounds showed much higher inhibitory activities at both cholinesterases in the Ellman test. Surprisingly, not only the quaternary salts, but also the uncharged tertiary compounds exhibited IC50 values at butyrylcholinesterase in the nanomolar range. Selectivity toward BChE of up to 76-fold was observed. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.03.011
• 作为产物：
  描述：

  5,8,9,13b-tetrahydro-6H-isoquino[1,2-a]isoquinolin-3-ol 、 1,6-二溴己烷 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以41%的产率得到3-{[6-(5,8,9,13b-tetrahydro-6H-isoquino[1,2-a]isoquinolin-3-yloxy)hexyl]oxy}-5,8,9,13b-tetrahydro-6H-isoquino[1,2-a]isoquinoline
  参考文献：
  名称：

  Bivalent 5,8,9,13b-tetrahydro-6H-isoquino[1,2-a]isoquinolines and -isoquinolinium salts: Novel heterocyclic templates for butyrylcholinesterase inhibitors

  摘要：

  Three different types of homobivalent compounds, 5,8,9,13b-tetrahydro-6H-isoqino[1,2-a]isoquinolines bearing tertiary N-atoms, their quaternary ammonium salts and their dibenzazecine analogues, connected by alkylene spacers of various lengths were synthesized. Compared to the therapeutically used inhibitor galanthamine, some of the bivalent compounds showed much higher inhibitory activities at both cholinesterases in the Ellman test. Surprisingly, not only the quaternary salts, but also the uncharged tertiary compounds exhibited IC50 values at butyrylcholinesterase in the nanomolar range. Selectivity toward BChE of up to 76-fold was observed. (C) 2010 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2010.03.011

文献信息

• Bivalent 5,8,9,13b-tetrahydro-6H-isoquino[1,2-a]isoquinolines and -isoquinolinium salts: Novel heterocyclic templates for butyrylcholinesterase inhibitors
  作者：Maria Schulze、Oliver Siol、Michael Decker、Jochen Lehmann

  DOI：10.1016/j.bmcl.2010.03.011

  日期：2010.5

  Three different types of homobivalent compounds, 5,8,9,13b-tetrahydro-6H-isoqino[1,2-a]isoquinolines bearing tertiary N-atoms, their quaternary ammonium salts and their dibenzazecine analogues, connected by alkylene spacers of various lengths were synthesized. Compared to the therapeutically used inhibitor galanthamine, some of the bivalent compounds showed much higher inhibitory activities at both cholinesterases in the Ellman test. Surprisingly, not only the quaternary salts, but also the uncharged tertiary compounds exhibited IC50 values at butyrylcholinesterase in the nanomolar range. Selectivity toward BChE of up to 76-fold was observed. (C) 2010 Elsevier Ltd. All rights reserved.