5,7-dimethoxy-3-(3-((4-(trifluoromethyl)benzyl)oxy)phenyl)-4H-chromen-4-one

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 异黄酮类化合物
• 英文名称: 5,7-dimethoxy-3-(3-((4-(trifluoromethyl)benzyl)oxy)phenyl)-4H-chromen-4-one
• 英文别名: 5,7-Dimethoxy-3-[3-[[4-(trifluoromethyl)phenyl]methoxy]phenyl]chromen-4-one；5,7-dimethoxy-3-[3-[[4-(trifluoromethyl)phenyl]methoxy]phenyl]chromen-4-one
• 化学式: C₂₅H₁₉F₃O₅
• 分子量: 456.418
• InChiKey: FSAZJPSATPWAAX-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.5
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  54
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  3-羟基苯乙酸 在 五氯化磷 、 三氟化硼乙醚 、 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 、 丙酮 为溶剂， 反应 4.08h， 生成 5,7-dimethoxy-3-(3-((4-(trifluoromethyl)benzyl)oxy)phenyl)-4H-chromen-4-one
  参考文献：
  名称：

  Synergistic inhibition of the Hedgehog pathway by newly designed Smo and Gli antagonists bearing the isoflavone scaffold

  摘要：

  Aberrant activation of the Hedgehog (Hh) pathway is responsible for the onset and progression of several malignancies. Small molecules able to block the pathway at the upstream receptor Smoothened (Smo) or the downstream effector Gli1 have thus emerged recently as valuable anticancer agents.Here, we have designed, synthesized, and tested new Hh inhibitors taking advantage by the highly versatile and privileged isoflavone scaffold. The introduction of specific substitutions on the isoflavone's ring B allowed the identification of molecules targeting preferentially Smo or Gli1. Biological assays coupled with molecular modeling corroborated the design strategy, and provided new insights into the mechanism of action of these molecules. The combined administration of two different isoflavones behaving as Smo and Gli antagonists, respectively, in primary medulloblastoma (MB) cells highlighted the synergistic effects of these agents, thus paving the way to further and innovative strategies for the pharmacological inhibition of Hh signaling. (C) 2018 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2018.07.017

文献信息

• Synergistic inhibition of the Hedgehog pathway by newly designed Smo and Gli antagonists bearing the isoflavone scaffold
  作者：Simone Berardozzi、Flavia Bernardi、Paola Infante、Cinzia Ingallina、Sara Toscano、Elisa De Paolis、Romina Alfonsi、Miriam Caimano、Bruno Botta、Mattia Mori、Lucia Di Marcotullio、Francesca Ghirga

  DOI：10.1016/j.ejmech.2018.07.017

  日期：2018.8

  Aberrant activation of the Hedgehog (Hh) pathway is responsible for the onset and progression of several malignancies. Small molecules able to block the pathway at the upstream receptor Smoothened (Smo) or the downstream effector Gli1 have thus emerged recently as valuable anticancer agents.Here, we have designed, synthesized, and tested new Hh inhibitors taking advantage by the highly versatile and privileged isoflavone scaffold. The introduction of specific substitutions on the isoflavone's ring B allowed the identification of molecules targeting preferentially Smo or Gli1. Biological assays coupled with molecular modeling corroborated the design strategy, and provided new insights into the mechanism of action of these molecules. The combined administration of two different isoflavones behaving as Smo and Gli antagonists, respectively, in primary medulloblastoma (MB) cells highlighted the synergistic effects of these agents, thus paving the way to further and innovative strategies for the pharmacological inhibition of Hh signaling. (C) 2018 Elsevier Masson SAS. All rights reserved.