4-(4-bromo-2,3-dihydro-1-benzo[b]oxepin-5-yl)-phenol | 791121-78-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并噁庚英
• 英文名称: 4-(4-bromo-2,3-dihydro-1-benzo[b]oxepin-5-yl)-phenol
• 英文别名: 4-bromo-5-(4-hydroxyphenyl)-2,3-dihydro-1-benzoxepin；4-(4-Bromo-2,3-dihydro-1-benzoxepin-5-yl)phenol
• CAS: 791121-78-3
• 化学式: C₁₆H₁₃BrO₂
• 分子量: 317.182
• InChiKey: OFICXDFTEHLIEN-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  19
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  29.5
• 氢给体数：
  1
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  4-(4-bromo-2,3-dihydro-1-benzo[b]oxepin-5-yl)-phenol 在 四(三苯基膦)钯 、 sodium carbonate 、 potassium carbonate 作用下， 以 四氢呋喃 、 丙酮 为溶剂， 反应 6.0h， 生成 2-[4-[4-(4-chlorophenyl)-2,3-dihydro-1-benzoxepin-5-yl]phenoxy]-N,N-dimethylethanamine
  参考文献：
  名称：

  Benzoxepin衍生的雌激素受体调节剂：一种新型的雌激素受体分子支架。

  摘要：

  我们目前并检查新型的基于苯并氧平的支架对人类雌激素受体的调节作用。通过呈现实验确定的对人MCF-7乳腺肿瘤细胞的抗增殖作用和测量的结合亲和力，可以检查这种新分子支架的受体耐受性。通过简短的计算与分子模拟的结构-活性关系研究，探讨了官能团取代对苯并氧杂支架的影响。

  DOI：

  10.1021/jm0495834
• 作为产物：
  描述：

  4-(2,3-dihydrobenzo[b]oxepin-5-yl)-phenol 在 pyridinium hydrobromide perbromide 作用下， 以 二氯甲烷 为溶剂， 以67%的产率得到4-(4-bromo-2,3-dihydro-1-benzo[b]oxepin-5-yl)-phenol
  参考文献：
  名称：

  Synthesis, biological evaluation, structural–activity relationship, and docking study for a series of benzoxepin-derived estrogen receptor modulators

  摘要：

  The estrogen receptors ER alpha and ER beta are recognized as important pharmaceutical targets for a variety of diseases including osteoporosis and breast cancer. A series of novel benzoxepin-derived compounds are described as potent selective modulators of the human estrogen receptor modulators (SERMs). We report the antiproliferative effects of these compounds on human MCF-7 breast tumor cells. These heterocyclic compounds contain the triarylethylene arrangement as exemplified by tamoxifen, conformationally restrained through the incorporation of the benzoxepin ring system. The compounds demonstrate potency at nanomolar concentrations in antiproliferative assays against an MCF-7 human breast cancer cell line with low cytotoxicity together with low nanomolar binding affinity for the estrogen receptor. The compounds also demonstrate potent antiestrogenic properties in the human uterine Ishikawa cell line. The effect of a number of functional group substitutions on the ER binding properties of the benzoxepin molecular scaffold is examined through a detailed docking and 2D-QSAR computational investigation. The best QSAR model developed for ER alpha beta selectivity yielded R-2 of 0.84 with an RMSE for the training set of 0.30. The predictive quality of the model was Q(2) of 0.72 and RMSE of 0.18 for the test set. One particular compound (26b) bearing a 4-fluoro substituent, exhibits 15-fold selectivity for ERb and both our docking and QSAR studies converge on the correlation between enhanced lipophilicity and enhanced ERb binding for this benzoxepin ring scaffold. (C) 2008 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2008.09.035

文献信息

• Benzoxepin-Derived Estrogen Receptor Modulators:  A Novel Molecular Scaffold for the Estrogen Receptor
  作者：David G. Lloyd、Rosario B. Hughes、Daniela M. Zisterer、D. Clive Williams、Caterina Fattorusso、Bruno Catalanotti、Giuseppe Campiani、Mary J. Meegan

  DOI：10.1021/jm0495834

  日期：2004.11.1

  efficacy of a novel benzoxepin-based scaffold for modulation of the human estrogen receptor. Receptor tolerance of this new molecular scaffold is examined through presentation of experimentally determined antiproliferative effects on human MCF-7 breast tumor cells and measured binding affinities. The effect of functional group substitution on the benzoxepin scaffold is explored through a brief computational

  我们目前并检查新型的基于苯并氧平的支架对人类雌激素受体的调节作用。通过呈现实验确定的对人MCF-7乳腺肿瘤细胞的抗增殖作用和测量的结合亲和力，可以检查这种新分子支架的受体耐受性。通过简短的计算与分子模拟的结构-活性关系研究，探讨了官能团取代对苯并氧杂支架的影响。
• Synthesis, biological evaluation, structural–activity relationship, and docking study for a series of benzoxepin-derived estrogen receptor modulators
  作者：Irene Barrett、Mary J. Meegan、Rosario B. Hughes、Miriam Carr、Andrew J.S. Knox、Natalia Artemenko、Georgia Golfis、Daniela M. Zisterer、David G. Lloyd

  DOI：10.1016/j.bmc.2008.09.035

  日期：2008.11

  The estrogen receptors ER alpha and ER beta are recognized as important pharmaceutical targets for a variety of diseases including osteoporosis and breast cancer. A series of novel benzoxepin-derived compounds are described as potent selective modulators of the human estrogen receptor modulators (SERMs). We report the antiproliferative effects of these compounds on human MCF-7 breast tumor cells. These heterocyclic compounds contain the triarylethylene arrangement as exemplified by tamoxifen, conformationally restrained through the incorporation of the benzoxepin ring system. The compounds demonstrate potency at nanomolar concentrations in antiproliferative assays against an MCF-7 human breast cancer cell line with low cytotoxicity together with low nanomolar binding affinity for the estrogen receptor. The compounds also demonstrate potent antiestrogenic properties in the human uterine Ishikawa cell line. The effect of a number of functional group substitutions on the ER binding properties of the benzoxepin molecular scaffold is examined through a detailed docking and 2D-QSAR computational investigation. The best QSAR model developed for ER alpha beta selectivity yielded R-2 of 0.84 with an RMSE for the training set of 0.30. The predictive quality of the model was Q(2) of 0.72 and RMSE of 0.18 for the test set. One particular compound (26b) bearing a 4-fluoro substituent, exhibits 15-fold selectivity for ERb and both our docking and QSAR studies converge on the correlation between enhanced lipophilicity and enhanced ERb binding for this benzoxepin ring scaffold. (C) 2008 Elsevier Ltd. All rights reserved.