5,8,9,13b-tetrahydro-6H-isoquino[1,2-a]isoquinolin-3-ol | 882673-56-5

• 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: 5,8,9,13b-tetrahydro-6H-isoquino[1,2-a]isoquinolin-3-ol
• 英文别名: 6,8,9,13b-tetrahydro-5H-isoquinolino[1,2-a]isoquinolin-3-ol
• CAS: 882673-56-5
• 化学式: C₁₇H₁₇NO
• 分子量: 251.328
• InChiKey: WKDIBUGWHRYVFS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  19
• 可旋转键数：
  0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.29
• 拓扑面积：
  23.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5,8,9,13b-tetrahydro-6H-isoquino[1,2-a]isoquinolin-3-ol 在 硝酸 、 溶剂黄146 作用下， 以 二氯甲烷 、 丙酮 为溶剂， 反应 26.0h， 生成 3-hydroxy-7-methyl-2-nitro-5,8,9,13b-tetrahydro-6H-isoquino[1,2-a]isoquinolinium iodide
  参考文献：
  名称：

  Dopamine/Serotonin Receptor Ligands. 12:  SAR Studies on Hexahydro-dibenz[d,g]azecines Lead to 4-Chloro-7-methyl-5,6,7,8,9,14-hexahydrodibenz[d,g]azecin-3-ol, the First Picomolar D₅-Selective Dopamine-Receptor Antagonist

  摘要：

  Hydroxylated, methoxylated, and/or chlorinated 7-methyl-5,6,7,8,9,14-hexahydrodibenz[d,g]azecines were generally synthesized out of substituted 2-phenylethylamines and isochromanones by Bischler-Napieralski cyclization of the resulting benzamides to dibenzoquinolizines and the quaternization and cleavage of the central C-N bond under Birch conditions. Chlorination of 2-phenylethylamines was useful for the site direction of cyclization, but chlorine atoms were removed under Birch conditions so that chlorination had to be repeated to get the respective chlorinated dibenz[dg]azecines. The target compounds were tested for their affinity at the different human-cloned dopamine-receptor subtypes (D-1 family, D-2 family). Generally, hydroxylation and chlorination of the dibenz-azecines increased affinities significantly. 1-Chloro-2-hydroxyhexahydro-dibenz[d,g]azecine was a subnanomolar antagonist at both subtype families. 4-Chloro-3-hydroxy7-methyl-5,6,7,8,9,14-hexahydro-dibenz[d,g]azecine was identified as the most potent and selective dopamine D-5 receptor ligand described to date with K-i(D-1) = 0.83, K-i(D-2L) = 4.0, K-i(D-3) = 24.6, K-i(D-4) = 5.2 nM, and K-i(D-5) = 57 pM (radioligand binding experiments), respectively.

  DOI：

  10.1021/jm051237e
• 作为产物：
  描述：

  3-methoxy-5,8,9,13b-tetrahydro-6H-isoquino[1,2-a]isoquinoline 在 氢溴酸 、 溶剂黄146 作用下， 反应 5.0h， 生成 5,8,9,13b-tetrahydro-6H-isoquino[1,2-a]isoquinolin-3-ol
  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.
• Dopamine/Serotonin Receptor Ligands. 12:  SAR Studies on Hexahydro-dibenz[<i>d</i>,<i>g</i>]azecines Lead to 4-Chloro-7-methyl-5,6,7,8,9,14-hexahydrodibenz[<i>d,g</i>]azecin-3-ol, the First Picomolar D₅-Selective Dopamine-Receptor Antagonist
  作者：Patrick Mohr、Michael Decker、Christoph Enzensperger、Jochen Lehmann

  DOI：10.1021/jm051237e

  日期：2006.3.1

  Hydroxylated, methoxylated, and/or chlorinated 7-methyl-5,6,7,8,9,14-hexahydrodibenz[d,g]azecines were generally synthesized out of substituted 2-phenylethylamines and isochromanones by Bischler-Napieralski cyclization of the resulting benzamides to dibenzoquinolizines and the quaternization and cleavage of the central C-N bond under Birch conditions. Chlorination of 2-phenylethylamines was useful for the site direction of cyclization, but chlorine atoms were removed under Birch conditions so that chlorination had to be repeated to get the respective chlorinated dibenz[dg]azecines. The target compounds were tested for their affinity at the different human-cloned dopamine-receptor subtypes (D-1 family, D-2 family). Generally, hydroxylation and chlorination of the dibenz-azecines increased affinities significantly. 1-Chloro-2-hydroxyhexahydro-dibenz[d,g]azecine was a subnanomolar antagonist at both subtype families. 4-Chloro-3-hydroxy7-methyl-5,6,7,8,9,14-hexahydro-dibenz[d,g]azecine was identified as the most potent and selective dopamine D-5 receptor ligand described to date with K-i(D-1) = 0.83, K-i(D-2L) = 4.0, K-i(D-3) = 24.6, K-i(D-4) = 5.2 nM, and K-i(D-5) = 57 pM (radioligand binding experiments), respectively.