1-(2-[4-(4-bromo-8-fluoro-2,3-dihydro-benzo[b]oxepin-5-yl)-phenoxy]-ethyl)-pyrrolidine | 1093116-33-6

• 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: 1-(2-[4-(4-bromo-8-fluoro-2,3-dihydro-benzo[b]oxepin-5-yl)-phenoxy]-ethyl)-pyrrolidine
• CAS: 1093116-33-6
• 化学式: C₂₂H₂₃BrFNO₂
• 分子量: 432.333
• InChiKey: SMEYGCKQXOHECV-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.24
• 重原子数：
  27.0
• 可旋转键数：
  5.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  21.7
• 氢给体数：
  0.0
• 氢受体数：
  3.0

反应信息

• 作为反应物：
  描述：

  1-(2-[4-(4-bromo-8-fluoro-2,3-dihydro-benzo[b]oxepin-5-yl)-phenoxy]-ethyl)-pyrrolidine 、 3-羟基苯硼酸 在 四(三苯基膦)钯 、 sodium carbonate 作用下， 以 四氢呋喃 、 水 为溶剂， 生成 3-(8-fluoro-5-[4-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-2,3-dihydro-benzo[b]oxepin-4-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
• 作为产物：
  描述：

  4-(4-bromo-8-fluoro-2,3-dihydro-benzo[b]oxepin-5-yl)-phenol 、 N-(2-氯乙基)吡咯烷盐酸盐 在 potassium carbonate 作用下， 以 丙酮 为溶剂， 以81%的产率得到1-(2-[4-(4-bromo-8-fluoro-2,3-dihydro-benzo[b]oxepin-5-yl)-phenoxy]-ethyl)-pyrrolidine
  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