6-甲氧基-2-(4-甲氧基苯基)-1H-吲哚-3-甲醛 | 158611-24-6

• 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
• 中文名称: 6-甲氧基-2-(4-甲氧基苯基)-1H-吲哚-3-甲醛
• 英文名称: 6-Methoxy-2-(4-methoxyphenyl)-indol-3-carbaldehyd
• 英文别名: 6-methoxy-2-(4-methoxyphenyl)-1H-indole-3-carbaldehyde
• CAS: 158611-24-6
• 化学式: C₁₇H₁₅NO₃
• 分子量: 281.311
• InChiKey: OISNBKYGHVZZNL-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：

  6-甲氧基-2-(4-甲氧基苯基)-1H-吲哚-3-甲醛 在 三溴化硼 作用下， 以 二氯甲烷 为溶剂， 反应 2.0h， 以56%的产率得到6-Hydroxy-2-(4-hydroxyphenyl)-indol-3-carbaldehyd
  参考文献：
  名称：

  3-取代的 2-苯基吲哚：合成和生物学特性

  摘要：

  吲哚 - 3 - 甲醛 5a、b 和 7a、b 与硝基甲烷的 Knoevenagel 反应生成硝基乙烯 12 和 14，与丙腈的类似反应生成亚甲基丙二酸二腈 16。硝基甲烷与 12 和 14 的迈克尔加成导致3-二硝基丙烷 13 和 15，16 还原为亚甲基丙二酸二腈 17.- 吲哚 3 与正丁基锂/苯磺酰氯反应生成 3-氯吲哚 18，与 NaH/乙基碘反应以及醚裂解和乙酰氧基衍生物的酰化作用 19.-化合物 7-11、14-17 和 19 显示出对雌激素受体的亲和力。化合物 7b、9-11、17b 和 19b 抑制 MCF-7 和 MDA-MB-231 细胞的生长。确定IC50值并讨论结构-活性关系。

  DOI：

  10.1002/ardp.19943270804
• 作为产物：
  描述：

  在 盐酸 、 三甲基乙酸钾 、 caesium carbonate 、 二苯基环己基膦 、 palladium(II) bromide 、 三氯氧磷 作用下， 以 1,4-二氧六环 、 水 、 乙腈 为溶剂， 反应 14.0h， 生成 6-甲氧基-2-(4-甲氧基苯基)-1H-吲哚-3-甲醛
  参考文献：
  名称：

  通过 C-H 激活和二氮杂环丙烷双胺化序列 Pd 催化的吲哚合成

  摘要：

  这项工作描述了一种有效的 Pd 催化吲哚合成。可以从容易获得的乙烯基溴以良好的收率获得多种吲哚。该反应可能通过连续的芳基 C-H 活化和所得的钯 (II) 环与二氮丙啶酮的双胺化进行。

  DOI：

  10.1021/acs.orglett.1c02757

文献信息

• Divergent and Orthogonal Approach to Carbazoles and Pyridoindoles from Oxindoles via Indole Intermediates
  作者：Tirtha Mandal、Gargi Chakraborti、Shilpi Karmakar、Jyotirmayee Dash

  DOI：10.1021/acs.orglett.8b01827

  日期：2018.8.17

  regiospecific approach to 2- and 2,3-disubstituted indole derivatives in high yields via a one-pot aromatization driven dehydration pathway. This method allows a convenient preparation of diallyl indoles that are used as ring-closing metathesis (RCM) precursors for the orthogonal synthesis of pyrido[1,2-a]indoles and carbazoles. The synthetic utility of this method is illustrated by the synthesis of a microtubulin

  以前未开发的将格利雅（Grignard）添加到羟吲哚中的方法通过一锅芳构化驱动的脱水途径，以高收率提供了一种区域特异性的方法，用于2-和2,3-二取代的吲哚衍生物。这种方法可以方便地制备用作烯丙基[1,2- a ]吲哚和咔唑的正交合成的闭环复分解（RCM）前体的二烯丙基吲哚。该方法的合成效用通过微管蛋白抑制剂和天然存在的咔唑生物碱的合成来说明。
• Antimitotic activities of 2-phenylindole-3-carbaldehydes in human breast cancer cells
  作者：Doris Kaufmann、Michaela Pojarová、Susanne Vogel、Renate Liebl、Robert Gastpar、Dietmar Gross、Tsuyuki Nishino、Tobias Pfaller、Erwin von Angerer

  DOI：10.1016/j.bmc.2007.05.030

  日期：2007.8

  Small molecules such as indoles are attractive as inhibitors of tubulin polymerization. Thus a number of 2-phenylindole-3-carbaldehydes with lipophilic substituents in both aromatic rings was synthesized and evaluated for antitumor activity in MDA-MB 231 and MCF-7 breast cancer cells. Some 5-alkylindole derivatives with a 4-methoxy group in the 2-phenyl ring strongly inhibit the growth of breast cancer cells with IC50 values of 5-20 nM. Their action can be rationalized by the cell cycle arrest in G(2)/M phase due to the inhibition of tubulin polymerization. (c) 2007 Elsevier Ltd. All rights reserved.
• 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.
• Mahboobi Siavosh, Grothus Goetz, von Angerer Erwin, Arch. Pharm., 327 (1994) N 8, S 481-492
  作者：Mahboobi Siavosh, Grothus Goetz, von Angerer Erwin

  DOI：——

  日期：——