2-(4-hydroxy-3-methoxyphenyl)-1-(2-hydroxy-4,6-dimethoxyphenyl)ethanone

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 二苯乙烯类
• 英文名称: 2-(4-hydroxy-3-methoxyphenyl)-1-(2-hydroxy-4,6-dimethoxyphenyl)ethanone
• 英文别名: 1-(2-Hydroxy-4,6-dimethoxyphenyl)-2-(4-hydroxy-3-methoxyphenyl)ethanone；1-(2-hydroxy-4,6-dimethoxyphenyl)-2-(4-hydroxy-3-methoxyphenyl)ethanone
• 化学式: C₁₇H₁₈O₆
• 分子量: 318.326
• InChiKey: QCKTULXUMQWFDY-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  23
• 可旋转键数：
  6
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.24
• 拓扑面积：
  85.2
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-(4-hydroxy-3-methoxyphenyl)-1-(2-hydroxy-4,6-dimethoxyphenyl)ethanone 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 2.58h， 生成 (E)-3-(4-((3,7-dimethylocta-2,6-dien-1-yl)oxy)-3-methoxyphenyl)-5,7-dimethoxy-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
• 作为产物：
  描述：

  3,5-二甲氧基苯酚 、 高香草酸 在 三氟化硼乙醚 作用下， 反应 1.5h， 以55%的产率得到2-(4-hydroxy-3-methoxyphenyl)-1-(2-hydroxy-4,6-dimethoxyphenyl)ethanone
  参考文献：
  名称：

  [EN] MULTITARGET HEDGEHOG PATHWAY INHIBITORS AND USES THEREOF
  [FR] INHIBITEURS MULTICIBLES DE LA VOIE HEDGEHOG ET LEURS UTILISATIONS

  摘要：

  本发明涉及选择性抑制Hedgehog（Hh）通路活性的化合物，以及它们的制备和用途。本发明的化合物在治疗依赖于Hh的肿瘤，如髓母细胞瘤（MB）方面具有用途。

  公开号：

  WO2014207069A1

文献信息

• [EN] MULTITARGET HEDGEHOG PATHWAY INHIBITORS AND USES THEREOF<br/>[FR] INHIBITEURS MULTICIBLES DE LA VOIE HEDGEHOG ET LEURS UTILISATIONS
  申请人：UNIV SIENA

  公开号：WO2014207069A1

  公开（公告）日：2014-12-31

  The present invention concerns compounds that selectively inhibit the activity of the Hedgehog (Hh) pathway, their preparation and uses thereof. The compounds of the present invention are useful in treating Hh-dependent tumors, such as medulloblastoma (MB).

  本发明涉及选择性抑制Hedgehog（Hh）通路活性的化合物，以及它们的制备和用途。本发明的化合物在治疗依赖于Hh的肿瘤，如髓母细胞瘤（MB）方面具有用途。
• MULTITARGET HEDGEHOG PATHWAY INHIBITORS AND USES THEREOF
  申请人：UNIVERSITA' DEGLI STUDI DI SIENA

  公开号：US20160368886A1

  公开（公告）日：2016-12-22

  The present invention concerns compounds that selectively inhibit the activity of the Hedgehog (Hh) pathway, their preparation and uses thereof. The compounds of the present invention are useful in treating Hh-dependent tumors, such as medulloblastoma (MB).
• 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.