1-(3,4,5-trimethoxyphenyl)-3-(4-methoxyphenylamino)prop-2-en-1-one | 1379535-44-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1-(3,4,5-trimethoxyphenyl)-3-(4-methoxyphenylamino)prop-2-en-1-one
• 英文别名: (Z)-3-(4-methoxyphenylamino)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one；(Z)-3-(4-methoxyanilino)-1-(3,4,5-trimethoxyphenyl)prop-2-en-1-one
• CAS: 1379535-44-0
• 化学式: C₁₉H₂₁NO₅
• 分子量: 343.379
• InChiKey: IBIXFMIFCOIBJZ-KTKRTIGZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.8
• 重原子数：
  25
• 可旋转键数：
  8
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  66
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为产物：
  描述：

  1-(3,4,5-trimethoxyphenyl)prop-2-yn-1-ol 在 2-碘酰基苯甲酸 作用下， 以 乙醇 、 二甲基亚砜 为溶剂， 反应 9.0h， 生成 1-(3,4,5-trimethoxyphenyl)-3-(4-methoxyphenylamino)prop-2-en-1-one
  参考文献：
  名称：

  (Z)-1-Aryl-3-arylamino-2-propen-1-ones, Highly Active Stimulators of Tubulin Polymerization: Synthesis, Structure–Activity Relationship (SAR), Tubulin Polymerization, and Cell Growth Inhibition Studies

  摘要：

  Tubulin, the major structural component of microtubules, is a target for the development of anticancer agents. A series of (Z)-1-aryl-3-arylamino-2-propen-1-one (10) were synthesized and evaluated for antiproliferative activity in cell-based assay. The most active compound (Z)-1-(2-bromo-3,4,5-trimethoxyphenyl)-3-(3-hydroxy-4-methoxyphenylamino)prop-2-en-1-one (10ae) was tested in 20 tumor cell lines including multidrug resistant phenotype and was found to induce apoptosis in all these cell lines with similar GI(50) values. Flow cytometry studies showed that 10ae arrested the cells in G2/M phase of cell cycle. In addition to G2/M block, these compounds caused microtubule stabilization like paclitaxel and induced apoptosis via activation of the caspase family. The observations made in this investigation demonstrate that (Z)-1-Aryl-3-arylamino-2-propen-1-one (10) represents a new class of microtubule-stabilizing agents.

  DOI：

  10.1021/jm300176j

文献信息

• Synthesis and antimitotic activity of alkoxy-substituted 1-aryl-3-(arylamino)alkenones
  作者：A. V. Samet、V. Yu. Zhuzhin、M. N. Semenova、V. V. Semenov

  DOI：10.1007/s11172-015-0883-9

  日期：2015.2

  The cis-trans isomerism of these compounds was studied. Biological tests on a sea urchin embryo model showed that 1-aryl-3-(arylamino)prop-2-en-1-ones exhibit an antimitotic effect both via microtubule destabilization and through the action on other cellular targets. The antiproliferative activity of these compounds increases with an increase in the number of alkoxy substituents in 1-aryl ring, whereas

  烷氧基取代的 1-aryl-3-(arylamino)prop-2-en-1-ones 和 1-aryl-3-(arylamino)but-2en-1-ones 通过将苯胺加成到 1,3-二氧代衍生物或芳基乙炔基酮。研究了这些化合物的顺反异构现象。对海胆胚胎模型的生物学测试表明，1-aryl-3-(arylamino)prop-2-en-1-ones 通过微管不稳定和对其他细胞目标的作用表现出抗有丝分裂作用。这些化合物的抗增殖活性随着 1-芳环中烷氧基取代基数量的增加而增加，而在对位存在一个甲氧基被证明对芳氨基部分是最佳的。
• (<i>Z</i>)-1-Aryl-3-arylamino-2-propen-1-ones, Highly Active Stimulators of Tubulin Polymerization: Synthesis, Structure–Activity Relationship (SAR), Tubulin Polymerization, and Cell Growth Inhibition Studies
  作者：M. V. Ramana Reddy、Balaiah Akula、Stephen C. Cosenza、Clement M. Lee、Muralidhar R. Mallireddigari、Venkat R. Pallela、D. R. C. Venkata Subbaiah、Andrew Udofa、E. Premkumar Reddy

  DOI：10.1021/jm300176j

  日期：2012.6.14

  Tubulin, the major structural component of microtubules, is a target for the development of anticancer agents. A series of (Z)-1-aryl-3-arylamino-2-propen-1-one (10) were synthesized and evaluated for antiproliferative activity in cell-based assay. The most active compound (Z)-1-(2-bromo-3,4,5-trimethoxyphenyl)-3-(3-hydroxy-4-methoxyphenylamino)prop-2-en-1-one (10ae) was tested in 20 tumor cell lines including multidrug resistant phenotype and was found to induce apoptosis in all these cell lines with similar GI(50) values. Flow cytometry studies showed that 10ae arrested the cells in G2/M phase of cell cycle. In addition to G2/M block, these compounds caused microtubule stabilization like paclitaxel and induced apoptosis via activation of the caspase family. The observations made in this investigation demonstrate that (Z)-1-Aryl-3-arylamino-2-propen-1-one (10) represents a new class of microtubule-stabilizing agents.