4-(5-acetoxy-7-hydroxy-4-oxo-4H-chromen-2-yl)phenylacetate | 34331-04-9

• 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: 4-(5-acetoxy-7-hydroxy-4-oxo-4H-chromen-2-yl)phenylacetate
• 英文别名: 4',5-diacetylapigenin；[4-(5-Acetyloxy-7-hydroxy-4-oxochromen-2-yl)phenyl] acetate；[4-(5-acetyloxy-7-hydroxy-4-oxochromen-2-yl)phenyl] acetate
• CAS: 34331-04-9
• 化学式: C₁₉H₁₄O₇
• 分子量: 354.316
• InChiKey: SDCIKEPOFQJCDF-UHFFFAOYSA-N

物化性质

• 沸点：
  582.9±50.0 °C(Predicted)
• 密度：
  1.400±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.02
• 重原子数：
  26.0
• 可旋转键数：
  3.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  103.04
• 氢给体数：
  1.0
• 氢受体数：
  7.0

反应信息

• 作为反应物：
  描述：

  4-(5-acetoxy-7-hydroxy-4-oxo-4H-chromen-2-yl)phenylacetate 在 magnesium(II) perchlorate 、 氨 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 26.0h， 生成 7-(tert-butoxy)-5-hydroxy-2-(4-hydroxyphenyl)-4H-chromen-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
• 作为产物：
  描述：

  德国春黄菊油 在 吡啶 、 咪唑 、 苯硫酚 作用下， 以 N-甲基吡咯烷酮 为溶剂， 反应 8.0h， 生成 4-(5-acetoxy-7-hydroxy-4-oxo-4H-chromen-2-yl)phenylacetate
  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

• Phosphoramidate protides of five flavones and their antiproliferative activity against HepG2 and L-O2 cell lines
  作者：Yue-qing Li、Fei Yang、Liu Wang、Zhi Cao、Tian-jiao Han、Zhe-ang Duan、Zhen Li、Wei-jie Zhao

  DOI：10.1016/j.ejmech.2016.02.012

  日期：2016.4

  A series of flavone-7-phosphoramidate derivatives were synthesized and tested for their antiproliferative activity in vitro against human hepatoma cell line HepG2 and human normal hepatic cell line L-O2. Compound 8d, 16d and 17d, incorporating the amino acid alanine, exhibited high inhibitory activity on HepG2 cell line with IC50 values of 9.0 mu mol/L, 5.5 mu mol/L and 6.6 mu mol/L. The introduction of acyl groups played a pivotal role in the selective inhibition toward human hepatoma HepG2 cells, except for compound 8a, 9a and 16b. Compound 8d, 16d and 17d could significantly induce G2/M arrest in HepG2 cells. Specially, Compound 16d could lead early apoptosis in HepG2 cells. (C) 2016 Elsevier Masson SAS. All rights reserved.