N-[2-(3-chloro-4-methoxyphenyl)ethyl]-2-(2-hydroxyethyl)benzamide | 882673-65-6

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: N-[2-(3-chloro-4-methoxyphenyl)ethyl]-2-(2-hydroxyethyl)benzamide
• CAS: 882673-65-6
• 化学式: C₁₈H₂₀ClNO₃
• 分子量: 333.815
• InChiKey: QTQZMFPMZJTTLY-UHFFFAOYSA-N

物化性质

• 熔点：
  104-112 °C(Solv: ethyl acetate (141-78-6))
• 沸点：
  539.7±50.0 °C(Predicted)
• 密度：
  1?+-.0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  58.6
• 氢给体数：
  2
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  N-[2-(3-chloro-4-methoxyphenyl)ethyl]-2-(2-hydroxyethyl)benzamide 在 吡啶 、 三氯氧磷 作用下， 以 氯仿 、 乙腈 为溶剂， 反应 19.5h， 生成
  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：

  异色瞒 、 2-(3-氯-4-甲氧基苯基)-乙胺 反应 5.0h， 以35%的产率得到N-[2-(3-chloro-4-methoxyphenyl)ethyl]-2-(2-hydroxyethyl)benzamide
  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

• 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.