trans-3-cyclohexyl-2,3-dihydro-1,4-benzodioxin-2-carboxylic acid <2-(2,6-dimethoxyphenoxy)ethyl>amide

• 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: trans-3-cyclohexyl-2,3-dihydro-1,4-benzodioxin-2-carboxylic acid <2-(2,6-dimethoxyphenoxy)ethyl>amide
• 英文别名: trans-3-cyclohexyl-2,3-dihydro-1,4-benzodioxin-2-carboxylic acid [2-(2,6-dimethoxyphenoxy)ethyl]amide；(2R,3S)-2-cyclohexyl-N-[2-(2,6-dimethoxyphenoxy)ethyl]-2,3-dihydro-1,4-benzodioxine-3-carboxamide
• 化学式: C₂₅H₃₁NO₆
• 分子量: 441.524
• InChiKey: AINFNAYVKCGCRQ-VWNXMTODSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.1
• 重原子数：
  32
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.48
• 拓扑面积：
  75.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  trans-3-cyclohexyl-2,3-dihydro-1,4-benzodioxin-2-carboxylic acid <2-(2,6-dimethoxyphenoxy)ethyl>amide 在 dimethyl sulfide borane 作用下， 以 二乙二醇二甲醚 为溶剂， 反应 12.0h， 生成 trans-<2-(2,6-dimethoxyphenoxy)ethyl><(3-cyclohexyl-2,3-dihydro-1,4-benzodioxin-2-yl)methyl>amine
  参考文献：
  名称：

  Structure-activity relationships in 1,4-benzodioxan-related compounds. 4. Effect of aryl and alkyl substituents at position 3 on .alpha.-adrenoreceptor blocking activity

  摘要：

  The observation that the insertion of a phenyl ring at position 3 of WB 4101 (1) afforded a potent and selective alpha1-adrenoreceptor antagonist, phendioxan (2), prompted us to further investigate that position of the 2,3-dihydro-1,4-benzodioxin moiety. Thus the 3-phenyl of 2 was replaced by methyl, isopropyl, cyclohexyl, or para-substituted phenyl groups either in a cis or a trans relationships affording compounds 3-17 and 58. The structure of these new derivatives was assigned on the basis of the coupling constant of hydrogens at positions 2 and 3 and confirmed by a crystallographic study. The blocking activity and relative selectivity of 3-17 on alpha1- and alpha2-adrenoreceptors were evaluated in the isolated rat vas deferens. The results were compared with those obtained for 1 and 2. All the compounds, with the exception of isopropyl and cyclohexyl derivatives 5-8, were effective al-adrenoreceptor antagonists with a significant alpha1/alpha2-selectivity. The lipophilic and/or electronic character of para substituents of the 3-phenyl ring does not alter markedly the affinity toward alpha1-adrenoreceptors. However, the 3-p-tolyl derivative 10 was slightly more potent and even more selective than 2.

  DOI：

  10.1021/jm00063a002
• 作为产物：
  描述：

  3-cyclohexylacrylic acid methyl ester 在 sodium hydroxide 、 溴 、 氯甲酸乙酯 、 potassium carbonate 、 三乙胺 作用下， 以 氯仿 、 丙酮 为溶剂， 反应 8.5h， 生成 trans-3-cyclohexyl-2,3-dihydro-1,4-benzodioxin-2-carboxylic acid <2-(2,6-dimethoxyphenoxy)ethyl>amide
  参考文献：
  名称：

  Structure-activity relationships in 1,4-benzodioxan-related compounds. 4. Effect of aryl and alkyl substituents at position 3 on .alpha.-adrenoreceptor blocking activity

  摘要：

  The observation that the insertion of a phenyl ring at position 3 of WB 4101 (1) afforded a potent and selective alpha1-adrenoreceptor antagonist, phendioxan (2), prompted us to further investigate that position of the 2,3-dihydro-1,4-benzodioxin moiety. Thus the 3-phenyl of 2 was replaced by methyl, isopropyl, cyclohexyl, or para-substituted phenyl groups either in a cis or a trans relationships affording compounds 3-17 and 58. The structure of these new derivatives was assigned on the basis of the coupling constant of hydrogens at positions 2 and 3 and confirmed by a crystallographic study. The blocking activity and relative selectivity of 3-17 on alpha1- and alpha2-adrenoreceptors were evaluated in the isolated rat vas deferens. The results were compared with those obtained for 1 and 2. All the compounds, with the exception of isopropyl and cyclohexyl derivatives 5-8, were effective al-adrenoreceptor antagonists with a significant alpha1/alpha2-selectivity. The lipophilic and/or electronic character of para substituents of the 3-phenyl ring does not alter markedly the affinity toward alpha1-adrenoreceptors. However, the 3-p-tolyl derivative 10 was slightly more potent and even more selective than 2.

  DOI：

  10.1021/jm00063a002

文献信息

• Structure-activity relationships in 1,4-benzodioxan-related compounds. 4. Effect of aryl and alkyl substituents at position 3 on .alpha.-adrenoreceptor blocking activity
  作者：Wilma Quaglia、Maria Pigini、Seyed K. Tayebati、Alessandro Piergentili、Mario Giannella、Gabriella Marucci、Carlo Melchiorre

  DOI：10.1021/jm00063a002

  日期：1993.5

  The observation that the insertion of a phenyl ring at position 3 of WB 4101 (1) afforded a potent and selective alpha1-adrenoreceptor antagonist, phendioxan (2), prompted us to further investigate that position of the 2,3-dihydro-1,4-benzodioxin moiety. Thus the 3-phenyl of 2 was replaced by methyl, isopropyl, cyclohexyl, or para-substituted phenyl groups either in a cis or a trans relationships affording compounds 3-17 and 58. The structure of these new derivatives was assigned on the basis of the coupling constant of hydrogens at positions 2 and 3 and confirmed by a crystallographic study. The blocking activity and relative selectivity of 3-17 on alpha1- and alpha2-adrenoreceptors were evaluated in the isolated rat vas deferens. The results were compared with those obtained for 1 and 2. All the compounds, with the exception of isopropyl and cyclohexyl derivatives 5-8, were effective al-adrenoreceptor antagonists with a significant alpha1/alpha2-selectivity. The lipophilic and/or electronic character of para substituents of the 3-phenyl ring does not alter markedly the affinity toward alpha1-adrenoreceptors. However, the 3-p-tolyl derivative 10 was slightly more potent and even more selective than 2.