7-((4-fluorobenzyl)oxy)-4-oxo-2-phenyl-4H-chromene-5,6-diyl diacetate | 1345982-10-6

• 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-fluorobenzyl)oxy)-4-oxo-2-phenyl-4H-chromene-5,6-diyl diacetate
• 英文别名: 5,6-diacetoxy-7-(4'-fluoro-benzyloxy)-flavone；[5-Acetyloxy-7-[(4-fluorophenyl)methoxy]-4-oxo-2-phenylchromen-6-yl] acetate
• CAS: 1345982-10-6
• 化学式: C₂₆H₁₉FO₇
• 分子量: 462.431
• InChiKey: CTBWZYDZLNUCNM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.2
• 重原子数：
  34
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.12
• 拓扑面积：
  88.1
• 氢给体数：
  0
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  7-((4-fluorobenzyl)oxy)-4-oxo-2-phenyl-4H-chromene-5,6-diyl diacetate 在 水 、 sodium hydroxide 作用下， 以 丙酮 为溶剂， 以84.6%的产率得到7-((4-fluorobenzyl)oxy)-5,6-dihydroxy-2-phenyl-4H-chromen-4-one
  参考文献：
  名称：

  Novel synthetic baicalein derivatives caused apoptosis and activated AMP-activated protein kinase in human tumor cells

  摘要：

  对新型黄岑酚衍生物的抗增殖活性研究表明，化合物8和9通过增强磷酸化AMPKα的水平激活AMPK，并且在A431、SK-OV-3、DU 145和HeLa细胞中表现出比黄岑酚和AICAR更强的抗增殖效果，提示了苄基黄岑酚在癌症治疗中的一种替代疗法。

  DOI：

  10.1039/c1ob06094e
• 作为产物：
  描述：

  黄芩素 在 sodium acetate 、 potassium carbonate 作用下， 以 丙酮 为溶剂， 生成 7-((4-fluorobenzyl)oxy)-4-oxo-2-phenyl-4H-chromene-5,6-diyl diacetate
  参考文献：
  名称：

  Novel synthetic baicalein derivatives caused apoptosis and activated AMP-activated protein kinase in human tumor cells

  摘要：

  对新型黄岑酚衍生物的抗增殖活性研究表明，化合物8和9通过增强磷酸化AMPKα的水平激活AMPK，并且在A431、SK-OV-3、DU 145和HeLa细胞中表现出比黄岑酚和AICAR更强的抗增殖效果，提示了苄基黄岑酚在癌症治疗中的一种替代疗法。

  DOI：

  10.1039/c1ob06094e

文献信息

• 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.