苯甲胺,3,4,5-三甲氧基-N-(3,4,5-三甲氧苯基)- | 134029-89-3

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 中文名称: 苯甲胺,3,4,5-三甲氧基-N-(3,4,5-三甲氧苯基)-
• 英文名称: (3,4,5-Trimethoxy-benzyl)-(3,4,5-trimethoxy-phenyl)-amine
• 英文别名: 3,4,5-Trimethoxy-N-(3,4,5-trimethoxybenzyl)aniline；3,4,5-trimethoxy-N-[(3,4,5-trimethoxyphenyl)methyl]aniline
• CAS: 134029-89-3
• 化学式: C₁₉H₂₅NO₆
• 分子量: 363.411
• InChiKey: CXRVPWLVIASLKP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.2
• 重原子数：
  26
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  67.4
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  苯甲胺,3,4,5-三甲氧基-N-(3,4,5-三甲氧苯基)- 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 6.0h， 生成 2-(benzo[d]thiazol-2-ylthio)-N-(3,4,5-trimethoxybenzyl)-N-(3,4,5-trimethoxyphenyl)acetamide
  参考文献：
  名称：

  通过抑制微管蛋白聚合并激活Hippo信号通路，在体外发现掺入苯并噻唑部分作为抗胃癌药物的叔酰胺衍生物。

  摘要：

  在我们先前关于抗微管蛋白和抗胃癌药物的研究的基础上，并继续进行，合成了结合苯并噻唑部分的新型叔酰胺衍生物，并在体外研究了其抗增殖活性。根据体外抗增殖活性结果探索了初步的结构活性关系（SAR）。某些化合物可以显着抑制三种癌细胞（HCT-116，MGC-803和PC-3细胞）的增殖，化合物F10对HCT-116细胞（IC 50  = 0.182μM），MGC-803细胞表现出优异的抗增殖活性（IC 50  = 0.035μM），PC-3细胞（IC 50  = 2.11μM）和SGC-7901细胞（IC50  = 0.049μM）。化合物F10有效抑制微管蛋白聚合（IC 50  = 1.9μM），并与微管蛋白的秋水仙碱结合位点结合。分子对接结果表明，化合物F10可以与β-微管蛋白的秋水仙碱结合位点紧密结合。此外，化合物F10可以调节Hippo / YAP信号通路。由于Hippo级联激活YAP，化合物F10从其最开始的MST1

  DOI：

  10.1016/j.ejmech.2020.112618
• 作为产物：
  描述：

  3,4,5-三甲氧基苯甲酰氯 在 吡啶 、 lithium aluminium tetrahydride 作用下， 以 四氢呋喃 为溶剂， 反应 8.0h， 生成 苯甲胺,3,4,5-三甲氧基-N-(3,4,5-三甲氧苯基)-
  参考文献：
  名称：

  Synthesis and evaluation of stilbene and dihydrostilbene derivatives as potential anticancer agents that inhibit tubulin polymerization

  摘要：

  An array of cis-, trans-, and dihydrostilbenes and some N-arylbenzylamines were synthesized and evaluated for their cytotoxicity in the five cancer cell cultures A-549 lung carcinoma, MCF-7 breast carcinoma, HT-29 colon adenocarcinoma, SKMEL-5 melanoma, and MLM melanoma. Several cis-stilbenes, structurally similar to combretastatins, were highly cytotoxic in all five cell lines and these were also found to be active as inhibitors of tubulin polymerization. The most active compounds also inhibited the binding of colchicine to tubulin. The most potent of the new compounds, both as a tubulin polymerization inhibitor and as a cytotoxic agent, was (Z)-1-(4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)ethene (5a). This substance was almost as potent as combretastatin A-4 (1a), the most active of the combretastatins, as a tubulin polymerization inhibitor. Compound 5a was found to be approximately 140 times more cytotoxic against HT-29 colon adenocarcinoma cells and about 10 times more cytotoxic against MCF-7 breast carcinoma cells than combretastatin A-4. However, 5a was found to be about 20 times less cytotoxic against A-549 lung carcinoma cells, 30 times less cytotoxic against SKMEL-5 melanoma cells, and 7 times less cytotoxic against MLM melanoma cells than combretastatin A-4. The relative potencies 5a > 8a > 6a for the cis, dihydro, and trans compounds, respectively, as inhibitors of tubulin polymerization are in agreement with the relative potencies previously observed for combretastatin A-4 (1a), dihydrocombretastatin A-4 (1c), and trans-combretastatin A-4 (1b). The relative potencies 5a > 8a > 6a were also reflected in the results of the cytotoxicity assays. Structure-activity relationships of this group of compounds are also discussed.

  DOI：

  10.1021/jm00112a036

文献信息

• Discovery of Novel 3,4-Dihydro-2(1H)-Quinolinone Sulfonamide Derivatives as New Tubulin Polymerization Inhibitors with Anti-Cancer Activity
  作者：Juan Ma、Guo-Hua Gong

  DOI：10.3390/molecules27051537

  日期：——

  4-tetrahydroquinoline-6-sulfonamide exhibited the strongest inhibitory effect on the proliferation of HeLa (IC50: 1.34 μM), and this value correlated well with the inhibitory activities of the compound against tubulin polymerization (IC50: 6.74 μM). In summary, a new type of quinoline-sulfonamide derivative with tubulin polymerization inhibitory activity was discovered, and it can be used as a lead compound for further

  本文合成了一小部分新型喹啉磺酰胺衍生物，并通过1H NMR和MS对其目标化合物的结构进行了确证。采用MTT法筛选了新靶点化合物对肿瘤细胞系的体外细胞毒活性。其中，化合物 D13 (N-(4-methoxybenzyl)-2-oxo-N-(3,4,5-trimethoxyphenyl)-1,2,3,4-tetrahydroquinoline-6-sulfonamide 对HeLa的增殖（IC50：1.34 μM），该值与该化合物对微管蛋白聚合的抑制活性（IC50：6.74 μM）有很好的相关性。综上所述，发现了一种新型的具有微管蛋白聚合抑制活性的喹啉-磺酰胺衍生物, 可作为先导化合物进行进一步改性。
• Design, synthesis and biological evaluation of 1,2,3-triazole benzothiazole derivatives as tubulin polymerization inhibitors with potent anti-esophageal cancer activities
  作者：Bo-Wen Wu、Wen-Jing Huang、Yun-He Liu、Qiu-Ge Liu、Jian Song、Tao Hu、Ping Chen、Sai-Yang Zhang

  DOI：10.1016/j.ejmech.2023.116118

  日期：2024.2

  esophageal cancer cells Kyse30 and EC-109 being the most sensitive to its effects (IC50 values were 0.042 and 0.038 μM, respectively). Compound K18 effectively inhibited tubulin polymerization (IC50 = 0.446 μM), thereby hindering tubulin polymerize into filamentous microtubules in Kyse30 and EC-109 cells. Additionally, compound K18 induced the degradation of oncogenic protein YAP via the UPS pathway. Based

  在本工作中，我们利用分子杂交策略设计并合成了新型1,2,3-三唑苯并噻唑衍生物K1-26 。探讨了其对MGC-803、Kyse30和HCT-116细胞的抗增殖活性，并初步对其构效关系进行了总结。其中，化合物K18的增殖抑制活性最强，食管癌细胞Kyse30和EC-109对其作用最敏感（IC 50值分别为0.042和0.038 μM）。化合物K18有效抑制微管蛋白聚合 (IC 50 = 0.446 μM)，从而阻碍 Kyse30 和 EC-109 细胞中微管蛋白聚合成丝状微管。此外，化合物K18通过UPS 途径诱导致癌蛋白 YAP 降解。基于这些分子水平的双重作用，化合物K18可以诱导Kyse30和EC-109细胞的G2/M期阻滞和细胞凋亡，并调节细胞周期和凋亡相关蛋白的表达水平。总之，我们的研究结果强调了一种新型的 1,2,3-三唑苯并噻唑衍生物K18 ，它具有治疗食道癌的巨大潜力。
• Synthesis and evaluation of stilbene and dihydrostilbene derivatives as potential anticancer agents that inhibit tubulin polymerization
  作者：Mark Cushman、Dhanapalan Nagarathnam、D. Gopal、Asit K. Chakraborti、Chii M. Lin、Ernest Hamel

  DOI：10.1021/jm00112a036

  日期：1991.8

  An array of cis-, trans-, and dihydrostilbenes and some N-arylbenzylamines were synthesized and evaluated for their cytotoxicity in the five cancer cell cultures A-549 lung carcinoma, MCF-7 breast carcinoma, HT-29 colon adenocarcinoma, SKMEL-5 melanoma, and MLM melanoma. Several cis-stilbenes, structurally similar to combretastatins, were highly cytotoxic in all five cell lines and these were also found to be active as inhibitors of tubulin polymerization. The most active compounds also inhibited the binding of colchicine to tubulin. The most potent of the new compounds, both as a tubulin polymerization inhibitor and as a cytotoxic agent, was (Z)-1-(4-methoxyphenyl)-2-(3,4,5-trimethoxyphenyl)ethene (5a). This substance was almost as potent as combretastatin A-4 (1a), the most active of the combretastatins, as a tubulin polymerization inhibitor. Compound 5a was found to be approximately 140 times more cytotoxic against HT-29 colon adenocarcinoma cells and about 10 times more cytotoxic against MCF-7 breast carcinoma cells than combretastatin A-4. However, 5a was found to be about 20 times less cytotoxic against A-549 lung carcinoma cells, 30 times less cytotoxic against SKMEL-5 melanoma cells, and 7 times less cytotoxic against MLM melanoma cells than combretastatin A-4. The relative potencies 5a > 8a > 6a for the cis, dihydro, and trans compounds, respectively, as inhibitors of tubulin polymerization are in agreement with the relative potencies previously observed for combretastatin A-4 (1a), dihydrocombretastatin A-4 (1c), and trans-combretastatin A-4 (1b). The relative potencies 5a > 8a > 6a were also reflected in the results of the cytotoxicity assays. Structure-activity relationships of this group of compounds are also discussed.
• Discovery of tertiary amide derivatives incorporating benzothiazole moiety as anti-gastric cancer agents in vitro via inhibiting tubulin polymerization and activating the Hippo signaling pathway
  作者：Jian Song、Qiu-Lei Gao、Bo-Wen Wu、Ting Zhu、Xin-Xin Cui、Cheng-Jun Jin、Shu-Yu Wang、Sheng-Hui Wang、Dong-Jun Fu、Hong-Min Liu、Sai-Yang Zhang、Yan-Bing Zhang、Yong-Chun Li

  DOI：10.1016/j.ejmech.2020.112618

  日期：2020.10

  the basis and continuation of our previous studies on anti-tubulin and anti-gastric cancer agents, novel tertiary amide derivatives incorporating benzothiazole moiety were synthesized and the antiproliferative activity was studied in vitro. Preliminary structure activity relationships (SARs) were explored according to the in vitro antiproliferative activity results. Some of compounds could significantly

  在我们先前关于抗微管蛋白和抗胃癌药物的研究的基础上，并继续进行，合成了结合苯并噻唑部分的新型叔酰胺衍生物，并在体外研究了其抗增殖活性。根据体外抗增殖活性结果探索了初步的结构活性关系（SAR）。某些化合物可以显着抑制三种癌细胞（HCT-116，MGC-803和PC-3细胞）的增殖，化合物F10对HCT-116细胞（IC 50  = 0.182μM），MGC-803细胞表现出优异的抗增殖活性（IC 50  = 0.035μM），PC-3细胞（IC 50  = 2.11μM）和SGC-7901细胞（IC50  = 0.049μM）。化合物F10有效抑制微管蛋白聚合（IC 50  = 1.9μM），并与微管蛋白的秋水仙碱结合位点结合。分子对接结果表明，化合物F10可以与β-微管蛋白的秋水仙碱结合位点紧密结合。此外，化合物F10可以调节Hippo / YAP信号通路。由于Hippo级联激活YAP，化合物F10从其最开始的MST1