5-methoxy-2-(4-methoxyphenyl)-1H-indole-3-carbaldehyde | 93316-36-0

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吲哚及其衍生物
• 英文名称: 5-methoxy-2-(4-methoxyphenyl)-1H-indole-3-carbaldehyde
• CAS: 93316-36-0
• 化学式: C₁₇H₁₅NO₃
• 分子量: 281.311
• InChiKey: KHFBMBBEXQAWTP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  51.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  5-methoxy-2-(4-methoxyphenyl)-1H-indole-3-carbaldehyde 在 三溴化硼 作用下， 以 氯仿 为溶剂， 反应 16.0h， 以92.9%的产率得到5-Hydroxy-2-(4-hydroxy-phenyl)-1H-indole-3-carbaldehyde
  参考文献：
  名称：

  一种巴多昔芬衍生物的制备方法

  摘要：

  本发明公开了一种巴多昔芬衍生物的合成方法，本发明以对甲氧基苯胺为原料，通过六步反应，实现巴多昔芬衍生物的合成。本发明提供的制备方法，工艺设计合理，可操作性强，反应条件比较温和，产率高，可实现工业化生产。本发明制备得到的巴多昔芬衍生物，对巴多昔芬进行质量、安全性和效能科学评价提供了重要依据，并且巴多昔芬衍生物药理活性好，可开发用于治疗骨质疏松症的药物，具有重要的应用价值。

  公开号：

  CN107033062B
• 作为产物：
  描述：

  5-甲氧基-2-(4-甲氧基苯基)吲哚 在 三氯氧磷 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 7.0h， 以76.06%的产率得到5-methoxy-2-(4-methoxyphenyl)-1H-indole-3-carbaldehyde
  参考文献：
  名称：

  一种巴多昔芬衍生物的制备方法

  摘要：

  本发明公开了一种巴多昔芬衍生物的合成方法，本发明以对甲氧基苯胺为原料，通过六步反应，实现巴多昔芬衍生物的合成。本发明提供的制备方法，工艺设计合理，可操作性强，反应条件比较温和，产率高，可实现工业化生产。本发明制备得到的巴多昔芬衍生物，对巴多昔芬进行质量、安全性和效能科学评价提供了重要依据，并且巴多昔芬衍生物药理活性好，可开发用于治疗骨质疏松症的药物，具有重要的应用价值。

  公开号：

  CN107033062B

文献信息

• Pd-^<i>t</i> BuONO Cocatalyzed Aerobic Indole Synthesis
  作者：Xiao-Shan Ning、Xin Liang、Kang-Fei Hu、Chuan-Zhi Yao、Jian-Ping Qu、Yan-Biao Kang

  DOI：10.1002/adsc.201701512

  日期：2018.4.17

  A Pd‐tBuONO co‐catalyzed scalable and practical synthesis of indoles with molecular oxygen as terminal oxidant is developed. Either terminal or internal 2‐vinylanilines could be smoothly converted to desired indoles under one general condition. This method has been evaluated in the large scale synthesis of indomethacin and a potential anti‐breast cancer drug candidate 1.

  甲的Pd-吨作为终端氧化剂被显影BUONO共催化的分子氧吲哚的可扩展性和实用的合成。在一种通用条件下，末端或内部2乙烯基苯胺均可顺利转化为所需的吲哚。吲哚美辛和潜在的抗乳腺癌候选药物1的大规模合成已对该方法进行了评估。
• Preparation and Application of Solid, Salt-Stabilized Zinc Amide Enolates with Enhanced Air and Moisture Stability
  作者：Yi-Hung Chen、Mario Ellwart、Georgios Toupalas、Yusuke Ebe、Paul Knochel

  DOI：10.1002/anie.201700216

  日期：2017.4.10

  various N‐morpholino amides with TMPZnCl⋅LiCl (TMP=2,2,6,6‐tetramethylpiperidyl) and Mg(OPiv)2 in THF at 25 °C provides solid zinc enolates with enhanced air and moisture stability (t1/2 in air: 1–3 h) after solvent evaporation. These enolates undergo Pd‐ and Cu‐catalyzed cross‐couplings with (hetero)aryl bromides as well as allylic and benzylic halides. The arylated N‐morpholino amides were converted into

  在25°C下用TMPZnCl⋅LiCl（TMP = 2,2,6,6-四甲基哌啶基）和Mg（OPiv）2在THF中处理各种N-吗啉代酰胺可提供具有增强的空气和湿气稳定性的固体烯醇锌（t 1溶剂蒸发后，在空气中/ 2（1-3小时）。这些烯醇化物与（杂）芳基溴化物以及烯丙基和苄基卤化物经历钯和铜催化的交叉偶联。所述芳基化的N-吗啉代酰胺通过的LaCl转化成各种酮3 ⋅2的LiCl介导的酰基化以格氏试剂。新的固体烯醇化物被用来分六个步骤制备有效的抗乳腺癌药物候选物，总产率为23％。
• Methoxy-Substituted 3-Formyl-2-phenylindoles Inhibit Tubulin Polymerization
  作者：Robert Gastpar、Michael Goldbrunner、Doris Marko、Erwin von Angerer

  DOI：10.1021/jm980228l

  日期：1998.12.1

  The aim of this study was the identification of the essential structural elements in the 12-formyl-5,6-dihydroindolo[2,1-a]isoquinoline system required for the inhibition of tubulin polymerization which is understood to be the predominant mode of action of this class of cytostatics. Since 2-phenylindole forms the main fragment of this tetracycle, it was used as the basic structure and modified with respect to the number and positions of the oxygen functions in the aromatic rings. Further modifications related to the nitrogen, which was both replaced by oxygen and sulfur and alkylated. All derivatives were tested for cytostatic activity in human breast cancer cells (MDA-MB 231, MCF-7) and inhibition of tubulin polymerization. The spectrum of activity ranged from inactive to IC50 values of 35 nM (cell growth inhibition) and 1.5 mu M (tubulin polymerization), respectively, for the most active derivative 3e (3-formyl-6-methoxy-2-(4-methoxyphenyl)indole). Although the correlation between antiproliferative activity and inhibition of tubulin polymerization was not very pronounced, all of the potent cytostatic agents in this study disrupted microtubule assembly completely at the standard concentration of 40 mu M. By fluorescence microscopy it was demonstrated that the derivative 3e degrades the cytoskeleton in a similar fashion as colchicine does leading to the condensation of the microtubules around the nucleus after treatment. The comparison between hydroxy and methoxy derivatives revealed st striking difference between the 2-phenylindole derivatives and the indoloisoquinolines. In the 2-phenylindole series, the methoxy compounds were much more effective than the free phenols, whereas in the tetracyclic system the effect of the hydroxy derivatives exceeded that of the methylated compounds by I order of magnitude. Preliminary studies on the binding mode showed that both the 2-phenylindole derivatives and the indoloisoquinolines bind to the colchicine site on tubulin.
• [(2-Phenylindol-3-yl)methylene]propanedinitriles inhibit the growth of breast cancer cells by cell cycle arrest in G2/M phase and apoptosis
  作者：Michaela Pojarová、Doris Kaufmann、Robert Gastpar、Tsuyuki Nishino、Przemyslaw Reszka、Patrick J. Bednarski、Erwin von Angerer

  DOI：10.1016/j.bmc.2007.07.046

  日期：2007.12

  Cell cycle arrest of malignant cells is an important option for cancer treatment. In this study, we modified the structure of antimitotic 2-phenylindole-3-carbaldehydes by condensation with malononitrile. The resulting methylene propanedinitriles inhibited the growth of MDA-MB 231 and MCF-7 breast cancer cells with IC50 values below 100 nM. Though they exhibited similar structure-activity relationships as the aldehydes, they did not inhibit tubulin polymerization but were capable of blocking the cell cycle in G(2)/M phase. The cell cycle arrest was accompanied by apoptosis as demonstrated by the activation of caspases 3 and 9. Since the new 2-phenylindole derivatives also inhibited the growth of transplanted MXT mouse mammary tumors, they are interesting candidates for further development. (C) 2007 Elsevier Ltd. All rights reserved.