1-methyl-5-(3,4,5-trimethoxybenzoyl)-1H-indole-3-carbaldehyde | 1427690-73-0

• 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: 1-methyl-5-(3,4,5-trimethoxybenzoyl)-1H-indole-3-carbaldehyde
• 英文别名: 1-Methyl-5-(3,4,5-trimethoxybenzoyl)indole-3-carbaldehyde；1-methyl-5-(3,4,5-trimethoxybenzoyl)indole-3-carbaldehyde
• CAS: 1427690-73-0
• 化学式: C₂₀H₁₉NO₅
• 分子量: 353.375
• InChiKey: WYVGABPGBUPWKI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.7
• 重原子数：
  26
• 可旋转键数：
  6
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  66.8
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1-methyl-5-(3,4,5-trimethoxybenzoyl)-1H-indole-3-carbaldehyde 在 sodium chlorite 、 sodium dihydrogenphosphate dihydrate 、 2-甲基-2-丁烯 作用下， 以 四氢呋喃 、 水 、 叔丁醇 为溶剂， 反应 12.0h， 以50%的产率得到1-Methyl-5-(3,4,5-trimethoxybenzoyl)indole-3-carboxylic acid
  参考文献：
  名称：

  Endowing Indole-Based Tubulin Inhibitors with an Anchor for Derivatization: Highly Potent 3-Substituted Indolephenstatins and Indoleisocombretastatins

  摘要：

  Colchicine site ligands with indole B rings are potent tubulin polymerization inhibitors. Structural modifications at the indole 3-position of 1-methyl-5-indolyl-based isocombretastatins (1,1-diarylethenes) and phenstatins endowed them with anchors for further derivatization and resulted in highly potent compounds. The substituted derivatives displayed potent cytotoxicity against several human cancer cell lines due to tubulin inhibition, as shown by cell cycle analysis, confocal microscopy, and tubulin polymerization inhibitory activity studies and promoted cell killing mediated by caspase-3 activation. Binding at the colchicine site was confirmed by means of fluorescence measurements of MTC displacement. Molecular modeling suggests that the tropolone-binding region of the colchicine site of tubulin can adapt to hosting small polar substituents. Isocombretastatins accepted substitutions better than phenstatins, and the highest potencies were achieved for the cyano and hydroxyiminomethyl substituents, with TPI values in the submicromolar range and cytotoxicities in the subnanomolar range. A 3,4,5-trimethoxyphenyl ring usually afforded more potent derivatives than a 2,3,4-trimethoxyphenyl ring.

  DOI：

  10.1021/jm3015603
• 作为产物：
  描述：

  5-溴吲哚 在 正丁基锂 、 sodium hydride 、 三氯氧磷 、 2-碘酰基苯甲酸 作用下， 以 四氢呋喃 、 正己烷 、 氯仿 、 二甲基亚砜 、 mineral oil 为溶剂， 反应 25.5h， 生成 1-methyl-5-(3,4,5-trimethoxybenzoyl)-1H-indole-3-carbaldehyde
  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

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。
• Endowing Indole-Based Tubulin Inhibitors with an Anchor for Derivatization: Highly Potent 3-Substituted Indolephenstatins and Indoleisocombretastatins
  作者：Raquel Álvarez、Pilar Puebla、J. Fernando Díaz、Ana C. Bento、Rósula García-Navas、Janis de la Iglesia-Vicente、Faustino Mollinedo、José Manuel Andreu、Manuel Medarde、Rafael Peláez

  DOI：10.1021/jm3015603

  日期：2013.4.11

  Colchicine site ligands with indole B rings are potent tubulin polymerization inhibitors. Structural modifications at the indole 3-position of 1-methyl-5-indolyl-based isocombretastatins (1,1-diarylethenes) and phenstatins endowed them with anchors for further derivatization and resulted in highly potent compounds. The substituted derivatives displayed potent cytotoxicity against several human cancer cell lines due to tubulin inhibition, as shown by cell cycle analysis, confocal microscopy, and tubulin polymerization inhibitory activity studies and promoted cell killing mediated by caspase-3 activation. Binding at the colchicine site was confirmed by means of fluorescence measurements of MTC displacement. Molecular modeling suggests that the tropolone-binding region of the colchicine site of tubulin can adapt to hosting small polar substituents. Isocombretastatins accepted substitutions better than phenstatins, and the highest potencies were achieved for the cyano and hydroxyiminomethyl substituents, with TPI values in the submicromolar range and cytotoxicities in the subnanomolar range. A 3,4,5-trimethoxyphenyl ring usually afforded more potent derivatives than a 2,3,4-trimethoxyphenyl ring.
• 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。