7-[(4-Fluorophenyl)methoxy]-5-hydroxy-2-phenylchromen-4-one | 306321-93-7

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 黄酮类化合物
• 英文名称: 7-[(4-Fluorophenyl)methoxy]-5-hydroxy-2-phenylchromen-4-one
• CAS: 306321-93-7
• 化学式: C₂₂H₁₅FO₄
• 分子量: 362.357
• InChiKey: LHIIZENBGYHAND-UHFFFAOYSA-N

物化性质

• 沸点：
  576.6±50.0 °C(Predicted)
• 密度：
  1.359±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  27
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  55.8
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为产物：
  描述：

  白杨素 、 4-氟溴苄 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 以95%的产率得到7-[(4-Fluorophenyl)methoxy]-5-hydroxy-2-phenylchromen-4-one
  参考文献：
  名称：

  Design and discovery of flavonoid-based HIV-1 integrase inhibitors targeting both the active site and the interaction with LEDGF/p75

  摘要：

  HIV integrase (IN) is an essential enzyme for the viral replication. Currently, three IN inhibitors have been approved for treating HIV-1 infection. All three drugs selectively inhibit the strand transfer reaction by chelating a divalent metal ion in the enzyme active site. Flavonoids are a well-known class of natural products endowed with versatile biological activities. Their beta-ketoenol or catechol structures can serve as a metal chelation motif and be exploited for the design of novel IN inhibitors. Using the metal chelation as a common pharmacophore, we introduced appropriate hydrophobic moieties into the flavonol core to design natural product-based novel IN inhibitors. We developed selective and efficient syntheses to generate a series of mono 3/5/7/3'/4'-substituted flavonoid derivatives. Most of these new compounds showed excellent HIV-1 IN inhibitory activity in enzyme-based assays and protected against HIV-1 infection in cell-based assays. The 7-morpholino substituted 7c showed effective antiviral activity (EC50 = 0.826 mu g/mL) and high therapeutic index (TI > 242). More significantly, these hydroxyflavones block the IN-LEDGF/p75 interaction with low-to sub-micromolar IC50 values and represent a novel scaffold to design new generation of drugs simultaneously targeting the catalytic site as well as protein-protein interaction domains. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2014.04.016

文献信息

• Evaluation and molecular docking study of two flavonoids from Oroxylum indicum (L.) Kurz and their semi-synthetic derivatives as histone deacetylase inhibitors
  作者：La-or Somsakeesit、Thanaset Senawong、Gulsiri Senawong、Pakit Kumboonma、Arunta Samankul、Narissara Namwan、Chavi Yenjai、Chanokbhorn Phaosiri

  DOI：10.1007/s11418-023-01758-y

  日期：2024.1
• Design and discovery of flavonoid-based HIV-1 integrase inhibitors targeting both the active site and the interaction with LEDGF/p75
  作者：Bo-Wen Li、Feng-Hua Zhang、Erik Serrao、Huan Chen、Tino W. Sanchez、Liu-Meng Yang、Nouri Neamati、Yong-Tang Zheng、Hui Wang、Ya-Qiu Long

  DOI：10.1016/j.bmc.2014.04.016

  日期：2014.6

  HIV integrase (IN) is an essential enzyme for the viral replication. Currently, three IN inhibitors have been approved for treating HIV-1 infection. All three drugs selectively inhibit the strand transfer reaction by chelating a divalent metal ion in the enzyme active site. Flavonoids are a well-known class of natural products endowed with versatile biological activities. Their beta-ketoenol or catechol structures can serve as a metal chelation motif and be exploited for the design of novel IN inhibitors. Using the metal chelation as a common pharmacophore, we introduced appropriate hydrophobic moieties into the flavonol core to design natural product-based novel IN inhibitors. We developed selective and efficient syntheses to generate a series of mono 3/5/7/3'/4'-substituted flavonoid derivatives. Most of these new compounds showed excellent HIV-1 IN inhibitory activity in enzyme-based assays and protected against HIV-1 infection in cell-based assays. The 7-morpholino substituted 7c showed effective antiviral activity (EC50 = 0.826 mu g/mL) and high therapeutic index (TI > 242). More significantly, these hydroxyflavones block the IN-LEDGF/p75 interaction with low-to sub-micromolar IC50 values and represent a novel scaffold to design new generation of drugs simultaneously targeting the catalytic site as well as protein-protein interaction domains. (C) 2014 Elsevier Ltd. All rights reserved.