(E)-4-(3-oxo-3-(2,4,6-trimethoxyphenyl)prop-1-en-1-yl)benzoic acid | 1017899-92-1

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 直链 1,3-二芳基丙烷
• 英文名称: (E)-4-(3-oxo-3-(2,4,6-trimethoxyphenyl)prop-1-en-1-yl)benzoic acid
• 英文别名: 4-[(E)-3-oxo-3-(2,4,6-trimethoxyphenyl)prop-1-enyl]benzoic acid
• CAS: 1017899-92-1
• 化学式: C₁₉H₁₈O₆
• 分子量: 342.348
• InChiKey: ICJRDTXRRVFKNB-RMKNXTFCSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.1
• 重原子数：
  25
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  82.1
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  (E)-4-(3-oxo-3-(2,4,6-trimethoxyphenyl)prop-1-en-1-yl)benzoic acid 在 草酰氯 、 N,N-二甲基甲酰胺 作用下， 以 二氯甲烷 为溶剂， 反应 3.5h， 生成 N,N-dimethyl-4-[(E)-3-oxo-3-(2,4,6-trimethoxyphenyl)prop-1-enyl]benzamide
  参考文献：
  名称：

  2'-Substituted chalcone derivatives as inhibitors of interleukin-1 biosynthesis

  摘要：

  A series of 2'-substituted chalcone derivatives has been found to show potent inhibition of the production of IL-1beta from human peripheral blood monocytes stimulated with lipopolysaccharide (LPS), with IC50 values in the 0.2-5.0-muM range. Some members of the series have also shown inhibition of septic shock induced in mice by injection of LPS, although with low potency. Qualitative structure-activity relationships have shown that the enone is required for activity, which may be mediated by conjugate addition of a biological nucleophile to the chalcone. Electron-poor aromatic rings beta to the ketone give enhanced potency. Although electronic effects in the other ring (directly attached to the ketone) are minimal, this ring must possess an ortho substituent for good activity without cytotoxicity, suggesting a degree of selectivity which would not be expected for simple, nonspecific alkylating agents.

  DOI：

  10.1021/jm00062a016
• 作为产物：
  描述：

  4-乙酰基苯甲酸 、 2,4,6-三甲氧基苯乙酮 在 sodium hydroxide 作用下， 以 甲醇 为溶剂， 以100%的产率得到(E)-4-(3-oxo-3-(2,4,6-trimethoxyphenyl)prop-1-en-1-yl)benzoic acid
  参考文献：
  名称：

  Mechanisms of action and structure-activity relationships of cytotoxic flavokawain derivatives

  摘要：

  22 Flavokawain derivatives (FKd) were obtained by one step syntheses in order to conduct a SAR study to understand the structural requirements for optimum and selective cytotoxicity. FKd and natural flavokawains A and B found into kava, a South Pacific traditional beverage, were evaluated against nine cancer and one healthy cell lines. The targeted cell cycle phases as well as the effects on the induction of apoptosis and cell cycle protein levels were investigated. Therapeutic improvements (more activity and selectivity) were achieved with FKd compared to natural flavokawains and notably with the 2',3,4',6'-tetramethoxychalcone (FKd 19). FKd induced a Gl/S arrest on p53 wild-type cells and an M arrest on p53 mutant-type, via the up-regulation of p21 and cyclin B1 proteins, followed by apoptosis. Moreover, FKd exhibited a 24 h-effect on Akt/mTor normal cells versus a 48 h-effect on Akt/mTor up-regulated cells. The SAR study resulted in the conclusion that trimethoxy A-ring allowed the best compromise between cytotoxicity and selectivity, as well as the substitution of the meta position on the B-ring and the use of halogens substituents. (C) 2017 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2017.01.049

文献信息

• Mechanisms of action and structure-activity relationships of cytotoxic flavokawain derivatives
  作者：Charlotte Thieury、Nicolas Lebouvier、Rémy Le Guével、Yann Barguil、Gaëtan Herbette、Cyril Antheaume、Edouard Hnawia、Yoshinori Asakawa、Mohammed Nour、Thierry Guillaudeux

  DOI：10.1016/j.bmc.2017.01.049

  日期：2017.3

  22 Flavokawain derivatives (FKd) were obtained by one step syntheses in order to conduct a SAR study to understand the structural requirements for optimum and selective cytotoxicity. FKd and natural flavokawains A and B found into kava, a South Pacific traditional beverage, were evaluated against nine cancer and one healthy cell lines. The targeted cell cycle phases as well as the effects on the induction of apoptosis and cell cycle protein levels were investigated. Therapeutic improvements (more activity and selectivity) were achieved with FKd compared to natural flavokawains and notably with the 2',3,4',6'-tetramethoxychalcone (FKd 19). FKd induced a Gl/S arrest on p53 wild-type cells and an M arrest on p53 mutant-type, via the up-regulation of p21 and cyclin B1 proteins, followed by apoptosis. Moreover, FKd exhibited a 24 h-effect on Akt/mTor normal cells versus a 48 h-effect on Akt/mTor up-regulated cells. The SAR study resulted in the conclusion that trimethoxy A-ring allowed the best compromise between cytotoxicity and selectivity, as well as the substitution of the meta position on the B-ring and the use of halogens substituents. (C) 2017 Elsevier Ltd. All rights reserved.
• 2'-Substituted chalcone derivatives as inhibitors of interleukin-1 biosynthesis
  作者：Douglas G. Batt、Robin Goodman、David G. Jones、Janet S. Kerr、Lisa R. Mantegna、Candice McAllister、Robert C. Newton、Sherrill Nurnberg、Patricia K. Welch、Maryanne B. Covington

  DOI：10.1021/jm00062a016

  日期：1993.5

  A series of 2'-substituted chalcone derivatives has been found to show potent inhibition of the production of IL-1beta from human peripheral blood monocytes stimulated with lipopolysaccharide (LPS), with IC50 values in the 0.2-5.0-muM range. Some members of the series have also shown inhibition of septic shock induced in mice by injection of LPS, although with low potency. Qualitative structure-activity relationships have shown that the enone is required for activity, which may be mediated by conjugate addition of a biological nucleophile to the chalcone. Electron-poor aromatic rings beta to the ketone give enhanced potency. Although electronic effects in the other ring (directly attached to the ketone) are minimal, this ring must possess an ortho substituent for good activity without cytotoxicity, suggesting a degree of selectivity which would not be expected for simple, nonspecific alkylating agents.