[2-(2,6-dimethoxyphenoxy)ethyl]{2-[2-(3-methoxybenzyloxy)phenoxy]ethyl}carbamic acid methyl ester | 907604-14-2

• 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: [2-(2,6-dimethoxyphenoxy)ethyl]{2-[2-(3-methoxybenzyloxy)phenoxy]ethyl}carbamic acid methyl ester
• 英文别名: methyl N-[2-(2,6-dimethoxyphenoxy)ethyl]-N-[2-[2-[(3-methoxyphenyl)methoxy]phenoxy]ethyl]carbamate
• CAS: 907604-14-2
• 化学式: C₂₈H₃₃NO₈
• 分子量: 511.572
• InChiKey: MMNXCMCBGOAWMN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.8
• 重原子数：
  37
• 可旋转键数：
  15
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.32
• 拓扑面积：
  84.9
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  [2-(2,6-dimethoxyphenoxy)ethyl]{2-[2-(3-methoxybenzyloxy)phenoxy]ethyl}carbamic acid methyl ester 在 氢氧化钾 作用下， 以 甲醇 为溶剂， 反应 48.0h， 以48%的产率得到N-[2-(2,6-dimethoxyphenoxy)ethyl]-2-[2-[(3-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]ethyl}[2-(2,6-dimethoxyphenoxy)ethyl]carbamic acid methyl ester 在 palladium on activated charcoal 氢气 、 potassium carbonate 、 溶剂黄146 作用下， 以 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 27.0h， 生成 [2-(2,6-dimethoxyphenoxy)ethyl]{2-[2-(3-methoxybenzyloxy)phenoxy]ethyl}carbamic acid methyl ester
  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

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.