5-(4-methoxyphenyl)-2,3-dihydro-1-benzoxepin | 791121-61-4

• 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: 5-(4-methoxyphenyl)-2,3-dihydro-1-benzoxepin
• 英文别名: 5-(4-Methoxyphenyl)-2,3-dihydro-1-benzoxepine
• CAS: 791121-61-4
• 化学式: C₁₇H₁₆O₂
• 分子量: 252.313
• InChiKey: BVBQEKFECVIYRX-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：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  18.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  5-(4-methoxyphenyl)-2,3-dihydro-1-benzoxepin 在 吡啶盐酸盐 、 pyridinium hydrobromide perbromide 、 zinc(II) chloride 作用下， 以 四氢呋喃 、 乙醚 、 正己烷 、 二氯甲烷 为溶剂， 反应 17.0h， 生成 5-(4-hydroxyphenyl)-4-phenyl-2,3-dihydro-1-benzoxepin
  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：

  (Z)-1-[4-ethoxy-1-(4-methoxyphenyl)but-1-en-1-yl]-2-(methoxymethoxy)benzene 在 三氟甲磺酸 作用下， 以 1,4-二氧六环 为溶剂， 反应 15.0h， 以62%的产率得到5-(4-methoxyphenyl)-2,3-dihydro-1-benzoxepin
  参考文献：
  名称：

  N-甲苯磺酰基-与邻位取代的芳基卤化物的钯催化偶联：4-芳基苯二甲基及相关杂环的合成

  摘要：

  已经开发了通过四个步骤序列合成4-芳基色烯，硫代色烯和相关杂环的方便和有效的方法。前三个步骤涉及炔烃的水合，的形成以及它们与邻位取代的芳基卤化物的Pd偶联，提供了立体选择性的Z-三取代的烯烃，而没有纯化每个阶段中产生的中间体。在最后的步骤中，证明后者是合适的前体，用于合成具有生物学意义的所需杂环。

  DOI：

  10.1016/j.tetlet.2010.12.093

文献信息

• Brønsted Acid‐Catalyzed Intramolecular 7‐<i>endo</i> Hydroarylation Reaction of 1,5‐Diaryl‐1‐pentynes
  作者：Kosho Makino、Shunsuke Sueki、Masahiro Anada

  DOI：10.1002/adsc.202300220

  日期：2023.5.12

  A Brønsted acid-catalyzed, transition metal-free intramolecular 7-endo hydroarylation reaction of 1,5-diaryl-1-pentynes has been developed. The use of 1,1,1,3,3,3-hexafluoro-2-propanol (HFIP) as a solvent was found to be critical for this process. Using the present methodology, we have accomplished the synthesis of KGP-18, an analogue of the anticancer natural product combretastatin A4.

  已开发出 1,5-二芳基-1-戊炔的Brønsted 酸催化、无过渡金属的分子内 7-内加氢芳基化反应。发现使用 1,1,1,3,3,3-六氟-2-丙醇 (HFIP) 作为溶剂对该过程至关重要。使用目前的方法，我们已经完成了 KGP-18 的合成，KGP-18 是抗癌天然产物 combretastatin A4 的类似物。
• 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.
• 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。
• Palladium-catalyzed coupling of N-tosylhydrazones with ortho substituted aryl halides: synthesis of 4-arylchromenes and related heterocycles
  作者：Evelia Rasolofonjatovo、Bret Tréguier、Olivier Provot、Abdallah Hamze、Estelle Morvan、Jean-Daniel Brion、Mouad Alami

  DOI：10.1016/j.tetlet.2010.12.093

  日期：2011.3

  A convenient and efficient procedure for the synthesis of 4-arylchromenes, thiochromenes, and related heterocycles via a four step-sequence has been developed. The first three steps, which involve hydration of alkynes, hydrazones formation, and their Pd-coupling with ortho substituted aryl halides, furnished stereoselectively Z-trisubstituted olefins without any purification of the intermediates generated

  已经开发了通过四个步骤序列合成4-芳基色烯，硫代色烯和相关杂环的方便和有效的方法。前三个步骤涉及炔烃的水合，的形成以及它们与邻位取代的芳基卤化物的Pd偶联，提供了立体选择性的Z-三取代的烯烃，而没有纯化每个阶段中产生的中间体。在最后的步骤中，证明后者是合适的前体，用于合成具有生物学意义的所需杂环。