(+/-)-trans-3-p-tolyl-2,3-dihydro-1,4-benzodioxin-2-carboxylic acid

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并二恶烷
• 英文名称: (+/-)-trans-3-p-tolyl-2,3-dihydro-1,4-benzodioxin-2-carboxylic acid
• 英文别名: trans-3-p-tolyl-2,3-dihydro-1,4-benzodioxin-2-carboxylic acid；(2R,3S)-2-(4-methylphenyl)-2,3-dihydro-1,4-benzodioxine-3-carboxylic acid
• 化学式: C₁₆H₁₄O₄
• 分子量: 270.285
• InChiKey: IMEOOEHKUOMZBN-CABCVRRESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  20
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.19
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (+/-)-trans-3-p-tolyl-2,3-dihydro-1,4-benzodioxin-2-carboxylic acid 在 氯甲酸乙酯 、 三乙胺 作用下， 反应 0.5h， 生成 (2R,3S)-(-)-3-p-tolyl-2,3-dihydro-1,4-benzodioxin-2-carboxylic acid [2-(2,6-dimethoxyphenoxy)ethyl]amide
  参考文献：
  名称：

  反式[2-（2,6-二甲氧基苯氧基）乙基] [（3-对甲苯基-2,3-二氢-1,4-苯并二恶英-2-基）的对映异构体的合成，绝对构型和生物学特征甲基]胺（甲吩二恶烷），一种有效的竞争性α1A肾上腺素受体拮抗剂。

  摘要：

  反-[2-（2,6-二甲氧基苯氧基）乙基] [（3-对甲苯基-2,3-二氢-1,4-苯并二恶英-2-基）甲基]胺的对映异构体（美芬二恶烷，2）是由手性反式-3-对甲苯基-2,3-二氢-1,4-苯并二恶英-2-羧酸[（+）-3和（-）-3]合成，而这些反过来是通过拆分（R）-和（S）-α-甲基苄胺的外消旋酸。比较2的对映体与（2S，3S）-3-甲基-2-苯基-1,4-苯并二恶烷的CD光谱，可以将2S，3S构型分配给2和3的（-）-对映体。 2R，3R构型与其他对映异构体的关系。与WB 4101（1），5-甲基尿嘧啶和（+）-尼古地平相比，在α1，α2，D2和5-HT1A受体处评估2的对映体的结合情况。此外，研究了两种对映体的天然和克隆的α1-肾上腺素受体亚型。在功能和结合试验中，（-）-2在α1-肾上腺素受体亚型上的效力是（+）-对映异构体的10-30倍。相对于α1b和α1d亚型，它对α1A

  DOI：

  10.1021/jm960069a
• 作为产物：
  描述：

  trans-3-p-tolyl-2,3-dihydro-1,4-benzodioxin-2-carboxylic acid methyl ester 在 硫酸 作用下， 以 乙醇 为溶剂， 反应 3.0h， 以21.8%的产率得到(+/-)-trans-3-p-tolyl-2,3-dihydro-1,4-benzodioxin-2-carboxylic acid
  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.
• Synthesis, Absolute Configuration, and Biological Profile of the Enantiomers of <i>trans</i>-[2-(2,6-Dimethoxyphenoxy)ethyl][(3-<i>p</i>-tolyl-2,3-dihydro-1,4- benzodioxin-2-yl)methyl]amine (Mephendioxan), a Potent Competitive α_1A-Adrenoreceptor Antagonist
  作者：Wilma Quaglia、Maria Pigini、Seyed K. Tayebati、Alessandro Piergentili、Mario Giannella、Amedeo Leonardi、Carlo Taddei、Carlo Melchiorre

  DOI：10.1021/jm960069a

  日期：1996.1.1

  enantiomers of 2 with that of (2S,3S)-3-methyl-2-phenyl-1,4-benzodioxane allowed the assignment of the 2S,3S configuration to the (-)-enantiomer of 2 and of the 2R,3R configuration to the other enantiomer. The binding profile of the enantiomers of 2 was assessed at alpha 1, alpha 2, D2, and 5-HT1A receptors, in comparison to WB 4101 (1), 5-methylurapidil, and (+)-niguldipine. In addition, the two enantiomers

  反-[2-（2,6-二甲氧基苯氧基）乙基] [（3-对甲苯基-2,3-二氢-1,4-苯并二恶英-2-基）甲基]胺的对映异构体（美芬二恶烷，2）是由手性反式-3-对甲苯基-2,3-二氢-1,4-苯并二恶英-2-羧酸[（+）-3和（-）-3]合成，而这些反过来是通过拆分（R）-和（S）-α-甲基苄胺的外消旋酸。比较2的对映体与（2S，3S）-3-甲基-2-苯基-1,4-苯并二恶烷的CD光谱，可以将2S，3S构型分配给2和3的（-）-对映体。 2R，3R构型与其他对映异构体的关系。与WB 4101（1），5-甲基尿嘧啶和（+）-尼古地平相比，在α1，α2，D2和5-HT1A受体处评估2的对映体的结合情况。此外，研究了两种对映体的天然和克隆的α1-肾上腺素受体亚型。在功能和结合试验中，（-）-2在α1-肾上腺素受体亚型上的效力是（+）-对映异构体的10-30倍。相对于α1b和α1d亚型，它对α1A