(1H-indol-5-yl)(3,4,5-trimethoxyphenyl)methanone | 946077-16-3

• 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: (1H-indol-5-yl)(3,4,5-trimethoxyphenyl)methanone
• 英文别名: 5-(3',4',5'-Trimethoxybenzoyl)indole；1H-indol-5-yl-(3,4,5-trimethoxyphenyl)methanone
• CAS: 946077-16-3
• 化学式: C₁₈H₁₇NO₄
• 分子量: 311.337
• InChiKey: MPXGSKMOQWDKQF-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  23
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  60.6
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  (1H-indol-5-yl)(3,4,5-trimethoxyphenyl)methanone 在 lithium hydroxide 、 potassium tert-butylate 作用下， 以 甲醇 、 水 、 乙腈 为溶剂， 反应 7.0h， 生成 2-[5-(3,4,5-Trimethoxybenzoyl)indol-1-yl]acetic acid
  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
• 作为产物：
  描述：

  5-吲哚甲醛 在 重铬酸吡啶 、 potassium tert-butylate 、 四丁基氟化铵 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 生成 (1H-indol-5-yl)(3,4,5-trimethoxyphenyl)methanone
  参考文献：
  名称：

  新型有效的抗有丝分裂杂环酮：合成，抗增殖活性和构效关系。

  摘要：

  我们报告了衍生自咔唑磺酰胺的新型杂环酮的合成，抗增殖活性和SAR。大多数杂环酮显示出强烈的细胞毒性。（N-1-甲基吲哚-5-基）-（3,4,5-三甲氧基苯基）-甲酮8b对7种人类肿瘤细胞系的细胞毒性最强（9.2-26 nM）。杂环酮的作用机理似乎涉及靶向微管蛋白，类似于CA-4的靶向，并且不同于咔唑磺酰胺。

  DOI：

  10.1016/j.bmcl.2007.04.048

文献信息

• Novel potent antimitotic heterocyclic ketones: Synthesis, antiproliferative activity, and structure–activity relationships
  作者：Laixing Hu、Jian-dong Jiang、Jinrong Qu、Yan Li、Jie Jin、Zhuo-rong Li、David W. Boykin

  DOI：10.1016/j.bmcl.2007.04.048

  日期：2007.7

  We report the synthesis, antiproliferative activity, and SAR of novel heterocyclic ketones derived from carbazole sulfonamides. Most of the heterocyclic ketones showed strong cytotoxicities. (N-1-Methylindole-5-yl)-(3,4,5-trimethoxyphenyl)-methanone 8b gave the most potent cytotoxicity (9.2-26 nM) against seven human tumor cell lines. The mechanism of action of the heterocyclic ketones appears to involve

  我们报告了衍生自咔唑磺酰胺的新型杂环酮的合成，抗增殖活性和SAR。大多数杂环酮显示出强烈的细胞毒性。（N-1-甲基吲哚-5-基）-（3,4,5-三甲氧基苯基）-甲酮8b对7种人类肿瘤细胞系的细胞毒性最强（9.2-26 nM）。杂环酮的作用机理似乎涉及靶向微管蛋白，类似于CA-4的靶向，并且不同于咔唑磺酰胺。
• 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。
• 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。
• 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.