Openphendioxan | 244123-03-3

• 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: Openphendioxan
• 英文别名: N-[2-(2,6-dimethoxyphenoxy)ethyl]-2-(2-phenylmethoxyphenoxy)ethanamine
• CAS: 244123-03-3
• 化学式: C₂₅H₂₉NO₅
• 分子量: 423.509
• InChiKey: ZQKYJYUHIBOEHV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  31
• 可旋转键数：
  13
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.28
• 拓扑面积：
  58.2
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  Openphendioxan 在 palladium on activated charcoal 氢氧化钾 、 氢气 、 potassium carbonate 、 溶剂黄146 、 三乙胺 作用下， 以 甲醇 、 氯仿 、 乙酸乙酯 、 N,N-二甲基甲酰胺 为溶剂， 125.0 ℃ 、344.74 kPa 条件下， 反应 79.0h， 生成 N-[2-(2,6-dimethoxyphenoxy)ethyl]-2-[2-[(2-methoxyphenyl)methoxy]phenoxy]ethanamine
  参考文献：
  名称：

  Structure−Activity Relationships in 1,4-Benzodioxan-Related Compounds. 8. {2-[2-(4-Chlorobenzyloxy)phenoxy]ethyl}-[2-(2,6-dimethoxyphenoxy)ethyl]amine (Clopenphendioxan) as a Tool to Highlight the Involvement of α_1D- and α_1B-Adrenoreceptor Subtypes in the Regulation of Human PC-3 Prostate Cancer Cell Apoptosis and Proliferation

  摘要：

  A series of new alpha(1)-adrenoreceptor antagonists (5-18) was prepared by introducing various substituents (Topliss approach) into the ortho, meta, and para positions of the benzyloxy function of the phendioxan open analogue 4 ("openphendioxan"). All the compounds synthesized were potent antagonists and generally displayed, similarly to 4, the highest affinity values at alpha(1D)-with respect to alpha(1A)- and alpha(1B)-AR subtypes and 5-HT1A subtype. By sulforhodamine B (SRB) assay on human PC-3 prostate cancer cells, the new compounds showed antitumor activity (estimated on the basis of three parameters GI(50), TGI, LC50), at low micromolar concentration, with 7 ("clopenphendioxan") exhibiting the highest efficacy. Moreover, this study highlighted for the first time alpha(1D)- and alpha(1B)-AR expression in PC3 cells and also demonstrated the involvement of these subtypes in the modulation of apoptosis and cell proliferation. A significant reduction of alpha(1D)- and alpha(1B)-AR expression in PC3 cells was associated with the apoptosis induced by 7. This depletion was completely reversed by norepinephrine.

  DOI：

  10.1021/jm0580398
• 作为产物：
  描述：

  2-(2-(benzyloxy)phenoxy)acetic acid 在 dimethyl sulfide borane 、 氯甲酸乙酯 、 三乙胺 作用下， 以 二乙二醇二甲醚 为溶剂， 反应 12.5h， 生成 Openphendioxan
  参考文献：
  名称：

  Structure−Activity Relationships in 1,4-Benzodioxan-Related Compounds. 6. Role of the Dioxane Unit on Selectivity for α₁-Adrenoreceptor Subtypes

  摘要：

  WB 4101-related benzodioxans 3-9 were synthesized, and their biological profiles at alpha(1)-adrenoreceptor subtypes and 5-HT1A serotoninergic receptors were assessed by binding assays in CHO and HeLa cells membranes expressing the human cloned receptors. Furthermore, receptor selectivity of selected benzodioxan derivatives was further determined in functional experiments in isolated rat vas deferens ((alpha(1A)) and aorta (alpha(1D)) and guinea pig spleen (alpha(1B)), in additional receptor binding assays in rat cortex membranes containing alpha(2)-adrenoreceptors and 5-HT2 serotoninergic receptors, and in rat striatum membranes containing D-2 dopaminergic receptors. An analysis of the results of receptor binding experiments for benzodioxan-modified derivatives 3-9 showed high affinity and selectivity toward the alpha(1a)-adrenoreceptor subtype for compounds 3-5 and 7 and a reversed selectivity profile for 9, which was a selective aid antagonist. Furthermore, the majority of structural modifications performed on the prototype 1 (WB 4101) led to a marked decrease in the affinity for 5-HT1A serotoninergic receptors, which may have relevance in the design of selective alpha(1A)-adrenoreceptor antagonists. The exception to these findings was the chromene derivative 8, which exhibited a 5-HT1A partial agonist profile.

  DOI：

  10.1021/jm9910324

文献信息

• Structure−Activity Relationships in 1,4-Benzodioxan-Related Compounds. 8. {2-[2-(4-Chlorobenzyloxy)phenoxy]ethyl}-[2-(2,6-dimethoxyphenoxy)ethyl]amine (Clopenphendioxan) as a Tool to Highlight the Involvement of α_1D- and α_1B-Adrenoreceptor Subtypes in the Regulation of Human PC-3 Prostate Cancer Cell Apoptosis and Proliferation
  作者：Wilma Quaglia、Giorgio Santoni、Maria Pigini、Alessandro Piergentili、Francesco Gentili、Michela Buccioni、Michela Mosca、Roberta Lucciarini、Consuelo Amantini、Massimo Ivan Nabissi、Patrizia Ballarini、Elena Poggesi、Amedeo Leonardi、Mario Giannella

  DOI：10.1021/jm0580398

  日期：2005.12.1

  A series of new alpha(1)-adrenoreceptor antagonists (5-18) was prepared by introducing various substituents (Topliss approach) into the ortho, meta, and para positions of the benzyloxy function of the phendioxan open analogue 4 ("openphendioxan"). All the compounds synthesized were potent antagonists and generally displayed, similarly to 4, the highest affinity values at alpha(1D)-with respect to alpha(1A)- and alpha(1B)-AR subtypes and 5-HT1A subtype. By sulforhodamine B (SRB) assay on human PC-3 prostate cancer cells, the new compounds showed antitumor activity (estimated on the basis of three parameters GI(50), TGI, LC50), at low micromolar concentration, with 7 ("clopenphendioxan") exhibiting the highest efficacy. Moreover, this study highlighted for the first time alpha(1D)- and alpha(1B)-AR expression in PC3 cells and also demonstrated the involvement of these subtypes in the modulation of apoptosis and cell proliferation. A significant reduction of alpha(1D)- and alpha(1B)-AR expression in PC3 cells was associated with the apoptosis induced by 7. This depletion was completely reversed by norepinephrine.
• Structure−Activity Relationships in 1,4-Benzodioxan-Related Compounds. 6. Role of the Dioxane Unit on Selectivity for α₁-Adrenoreceptor Subtypes
  作者：Wilma Quaglia、Maria Pigini、Alessandro Piergentili、Mario Giannella、Gabriella Marucci、Elena Poggesi、Amedeo Leonardi、Carlo Melchiorre

  DOI：10.1021/jm9910324

  日期：1999.7.1

  WB 4101-related benzodioxans 3-9 were synthesized, and their biological profiles at alpha(1)-adrenoreceptor subtypes and 5-HT1A serotoninergic receptors were assessed by binding assays in CHO and HeLa cells membranes expressing the human cloned receptors. Furthermore, receptor selectivity of selected benzodioxan derivatives was further determined in functional experiments in isolated rat vas deferens ((alpha(1A)) and aorta (alpha(1D)) and guinea pig spleen (alpha(1B)), in additional receptor binding assays in rat cortex membranes containing alpha(2)-adrenoreceptors and 5-HT2 serotoninergic receptors, and in rat striatum membranes containing D-2 dopaminergic receptors. An analysis of the results of receptor binding experiments for benzodioxan-modified derivatives 3-9 showed high affinity and selectivity toward the alpha(1a)-adrenoreceptor subtype for compounds 3-5 and 7 and a reversed selectivity profile for 9, which was a selective aid antagonist. Furthermore, the majority of structural modifications performed on the prototype 1 (WB 4101) led to a marked decrease in the affinity for 5-HT1A serotoninergic receptors, which may have relevance in the design of selective alpha(1A)-adrenoreceptor antagonists. The exception to these findings was the chromene derivative 8, which exhibited a 5-HT1A partial agonist profile.