(1-ethyl-1H-indol-5-yl)(3,4,5-trimethoxyphenyl)methanone | 951382-92-6

• 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
• 英文名称: (1-ethyl-1H-indol-5-yl)(3,4,5-trimethoxyphenyl)methanone
• 英文别名: (1-Ethylindol-5-yl)-(3,4,5-trimethoxyphenyl)methanone
• CAS: 951382-92-6
• 化学式: C₂₀H₂₁NO₄
• 分子量: 339.391
• InChiKey: SGMNXUMTQXRVFJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  25
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  49.7
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1-ethyl-1H-indol-5-yl)(3,4,5-trimethoxyphenyl)methanone 在 sodium hydroxide 、 三氯氧磷 作用下， 以 乙醇 、 氯仿 、 水 为溶剂， 反应 20.0h， 生成 (E)-3-(1-ethyl-5-(3,4,5-trimethoxybenzoyl)-1H-indol-3-yl)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one
  参考文献：
  名称：

  基于苯达他汀的吲哚连接查耳酮作为抗癌剂和微管蛋白聚合抑制剂的合成，生物学评估和分子对接分析

  摘要：

  设计并合成了一个新的基于phenstatin的吲哚连接查尔酮化合物（9a-z和9aa-ad）库。其中，在芳环中具有1-甲基，2-和3-甲氧基取代基的化合物9a对人类口腔癌细胞系SCC-29B，球体和口腔癌AW13516的小鼠异种移植模型有效。化合物9a通过破坏细胞完整性并影响葡萄糖代谢而表现出抗癌活性，这是癌症的标志。如通过对9a处理的SCC-29B细胞的免疫荧光测定所观察到的，细胞结构受到微管蛋白聚合抑制的影响。一种在体外微管蛋白聚合动力学分析提供了9a与微管蛋白直接相互作用的证据。微管蛋白和化合物9a之间的这种物理相互作用进一步通过表面等离子体共振（SPR）分析得到了证实。分子对接实验和验证表明，化合物9a在微管蛋白的秋水仙碱结合位点和葡萄糖代谢途径中关键酶的活性位点相互作用并结合。基于计算机模拟，生物物理相互作用和临床前的观察，由基于抑他汀的吲哚-查耳酮骨架组成的9a可被视为开发抗癌治疗剂的有吸引力的微管蛋白聚合抑制剂。

  DOI：

  10.1016/j.bioorg.2020.104447
• 作为产物：
  描述：

  5-吲哚甲醛 在 氢氧化钾 、 sodium hydroxide 、 重铬酸吡啶 、 4 A molecular sieve 、 potassium tert-butylate 、 四丁基硫酸氢铵 作用下， 以 四氢呋喃 、 乙醇 、 二氯甲烷 为溶剂， 反应 4.33h， 生成 (1-ethyl-1H-indol-5-yl)(3,4,5-trimethoxyphenyl)methanone
  参考文献：
  名称：

  4- and 5-Aroylindoles as Novel Classes of Potent Antitubulin Agents

  摘要：

  A novel series of 4- and 5-aroylindole derivatives was prepared and evaluated for antitumor activity. Several compounds showed excellent antiproliferative activity as inhibitors of tubulin polymerization. Compounds 13, 14, 15, and 18, with IC50 values of 1.9, 1.1, 1.2, and 1.8 mu M, respectively, exhibited more potent inhibition of tubulin polymerization than colchicine. They also displayed antiproliferative activity, with IC50 values ranging from 10 to 43 nM in a variety of human cell lines from different organs.

  DOI：

  10.1021/jm070557q

文献信息

• New (3-(1<i>H</i>-benzo[<i>d</i>]imidazol-2-yl))/(3-(3<i>H</i>-imidazo[4,5-<i>b</i>]pyridin-2-yl))-(1<i>H</i>-indol-5-yl)(3,4,5-trimethoxyphenyl)methanone conjugates as tubulin polymerization inhibitors
  作者：Kishore Mullagiri、V. Lakshma Nayak、Satish Sunkari、Geeta Sai Mani、Sravanthi Devi Guggilapu、Burri Nagaraju、Abdullah Alarifi、Ahmed Kamal

  DOI：10.1039/c7md00450h

  日期：——

  A series of new benzimidazole-indole linked phenstatin conjugates 4–6(a–i) were synthesized and evaluated for their anticancer activity.

  一系列新的苯并咪唑-吲哚连接的苯斯塔汀共轭物4-6(a-i)被合成并评估其抗癌活性。
• Isocombretastatins A: 1,1-Diarylethenes as potent inhibitors of tubulin polymerization and cytotoxic compounds
  作者：Raquel Álvarez、Concepción Álvarez、Faustino Mollinedo、Beatriz G. Sierra、Manuel Medarde、Rafael Peláez

  DOI：10.1016/j.bmc.2009.07.012

  日期：2009.9.1

  N-methyl- and N-ethyl-5-indolyl analogues of combretastatin A-4. Analogues with a 2,3,4-trimethoxyphenyl ring instead of the 3,4,5-trimethoxyphenyl ring have also been prepared. The isocombretastatins A strongly inhibit tubulin polymerization and are potent cytotoxic compounds, some of them with IC50s in the nanomolar range. This new family of tubulin inhibitors shows higher or comparable potency when compared

  异combretastatins A是康美他汀A的1,1-二芳基乙烯异构体。我们合成了combrestastatin A-4，脱氧康布他汀A-4、3-氨基-脱氧康布他汀A-4（AVE-8063），萘基康布他汀A和N-甲基-和康布雷他汀A-4的N-乙基-5-吲哚基类似物。还已经制备了具有2,3,4-三甲氧基苯基环而不是3,4,5-三甲氧基苯基环的类似物。异combretastatins A强烈抑制微管蛋白聚合，并且是有效的细胞毒性化合物，其中一些具有IC 50在纳摩尔范围内。与酚他汀或康维他汀类似物相比，这个新的微管蛋白抑制剂家族显示出更高或相当的效力。这些结果表明，具有双芳基双取代的一个碳桥可以成功地替代康美他汀的两个碳桥，并且苯他汀类的羰基对于高效能并不是必不可少的。
• Diarylmethyloxime and hydrazone derivatives with 5-indolyl moieties as potent inhibitors of tubulin polymerization
  作者：Concepción Álvarez、Raquel Álvarez、Purificación Corchete、José Luis López、Concepción Pérez-Melero、Rafael Peláez、Manuel Medarde

  DOI：10.1016/j.bmc.2008.04.054

  日期：2008.6

  We describe the synthesis and biological evaluation of a series of diarylmethyloxime and diarylmethylhydrazone analogues that contain an indole ring and different modi. cations on the nitrogen of the bridge. Several compounds showed potent tubulin polymerization inhibitory action as well as cytotoxic activity against cancer cell lines. The N-methyl-5-indolyl substituted analogues are more potent than ethyl substituted ones. The most potent inhibitors of tubulin polymerization are the diarylketones and the diaryloximes. The cytotoxicity against several cancer cell lines is lower for the oximes than for the ketones. Other substitutions on the imine nitrogen greatly reduce the tubulin inhibitory and/or cytotoxic potencies. (C) 2008 Elsevier Ltd. All rights reserved.
• Synthesis, biological evaluation, and molecular docking analysis of phenstatin based indole linked chalcones as anticancer agents and tubulin polymerization inhibitors
  作者：Jyoti Kode、Jeshma Kovvuri、Burri Nagaraju、Shailesh Jadhav、Madan Barkume、Subrata Sen、Nirmal Kumar Kasinathan、Pradip Chaudhari、Bhabani Shankar Mohanty、Jitendra Gour、Dilep Kumar Sigalapalli、C. Ganesh Kumar、Trupti Pradhan、Manisha Banerjee、Ahmed Kamal

  DOI：10.1016/j.bioorg.2020.104447

  日期：2020.12

  hallmark of cancer. The cellular architecture was affected by inhibition of tubulin polymerization as observed by an immunofluorescence assay on 9a-treated SCC-29B cells. An in vitro tubulin polymerization kinetics assay provided evidence of direct interaction of 9a with tubulin. This physical interaction between tubulin and compound 9a was further confirmed by Surface Plasmon Resonance (SPR) analysis. Molecular

  设计并合成了一个新的基于phenstatin的吲哚连接查尔酮化合物（9a-z和9aa-ad）库。其中，在芳环中具有1-甲基，2-和3-甲氧基取代基的化合物9a对人类口腔癌细胞系SCC-29B，球体和口腔癌AW13516的小鼠异种移植模型有效。化合物9a通过破坏细胞完整性并影响葡萄糖代谢而表现出抗癌活性，这是癌症的标志。如通过对9a处理的SCC-29B细胞的免疫荧光测定所观察到的，细胞结构受到微管蛋白聚合抑制的影响。一种在体外微管蛋白聚合动力学分析提供了9a与微管蛋白直接相互作用的证据。微管蛋白和化合物9a之间的这种物理相互作用进一步通过表面等离子体共振（SPR）分析得到了证实。分子对接实验和验证表明，化合物9a在微管蛋白的秋水仙碱结合位点和葡萄糖代谢途径中关键酶的活性位点相互作用并结合。基于计算机模拟，生物物理相互作用和临床前的观察，由基于抑他汀的吲哚-查耳酮骨架组成的9a可被视为开发抗癌治疗剂的有吸引力的微管蛋白聚合抑制剂。
• 4- and 5-Aroylindoles as Novel Classes of Potent Antitubulin Agents
  作者：Jing-Ping Liou、Chang-Ying Wu、Hsing-Pang Hsieh、Chi-Yen Chang、Chi-Ming Chen、Ching-Chuan Kuo、Jang-Yang Chang

  DOI：10.1021/jm070557q

  日期：2007.9.1

  A novel series of 4- and 5-aroylindole derivatives was prepared and evaluated for antitumor activity. Several compounds showed excellent antiproliferative activity as inhibitors of tubulin polymerization. Compounds 13, 14, 15, and 18, with IC50 values of 1.9, 1.1, 1.2, and 1.8 mu M, respectively, exhibited more potent inhibition of tubulin polymerization than colchicine. They also displayed antiproliferative activity, with IC50 values ranging from 10 to 43 nM in a variety of human cell lines from different organs.