3-chloro-2-methoxy-5,8,9,13b-tetrahydro-6H-isoquino[1,2-a]isoquinoline | 882673-69-0

• 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-chloro-2-methoxy-5,8,9,13b-tetrahydro-6H-isoquino[1,2-a]isoquinoline
• 英文别名: 3-chloro-2-methoxy-6,8,9,13b-tetrahydro-5H-isoquinolino[1,2-a]isoquinoline
• CAS: 882673-69-0
• 化学式: C₁₈H₁₈ClNO
• 分子量: 299.8
• InChiKey: PIIQJULISLTPEQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  21
• 可旋转键数：
  1
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.33
• 拓扑面积：
  12.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  3-chloro-2-methoxy-5,8,9,13b-tetrahydro-6H-isoquino[1,2-a]isoquinoline 在 氢溴酸 作用下， 以 丙酮 为溶剂， 反应 23.0h， 生成 3-chloro-7-methyl-6,8,9,13b-tetrahydro-5H-isoquinolino[1,2-a]isoquinolin-7-ium-2-ol;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：

  2-[2-({[2-(3-chloro-4-methoxyphenyl)ethyl]amino}carbonyl)phenyl]ethyl ethyl carbonate 在 氢氧化钾 、 sodium tetrahydroborate 、 三氯氧磷 作用下， 以 甲醇 、 乙醇 、 乙腈 为溶剂， 反应 34.75h， 生成 3-chloro-2-methoxy-5,8,9,13b-tetrahydro-6H-isoquino[1,2-a]isoquinoline
  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

文献信息

• Synthesis and Reactivity of Dibenz[d,g]azecin-14(5H)-ones
  作者：Michael Decker、Patrick Mohr、Jochen Lehmann

  DOI：10.3987/com-06-10681

  日期：——
• 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.