4-(5-acetoxy-4-oxo-7-(tosyloxy)-4H-chromen-2-yl)-1,2-phenylene diacetate | 1610737-84-2

• 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-4-oxo-7-(tosyloxy)-4H-chromen-2-yl)-1,2-phenylene diacetate
• CAS: 1610737-84-2
• 化学式: C₂₈H₂₂O₁₁S
• 分子量: 566.542
• InChiKey: DFXCZUNVFATWEQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.31
• 重原子数：
  40.0
• 可旋转键数：
  7.0
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.14
• 拓扑面积：
  152.48
• 氢给体数：
  0.0
• 氢受体数：
  11.0

反应信息

• 作为反应物：
  描述：

  4-(5-acetoxy-4-oxo-7-(tosyloxy)-4H-chromen-2-yl)-1,2-phenylene diacetate 在 氨 作用下， 以 甲醇 为溶剂， 反应 2.0h， 以80%的产率得到2-(3,4-dihydroxyphenyl)-5-hydroxy-4-oxo-4H-chromen-7-yl-4-methylbenzenesulfonate
  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：

  木犀草素 在 吡啶 、 咪唑 、 苯硫酚 、 三乙胺 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 为溶剂， 反应 10.0h， 生成 4-(5-acetoxy-4-oxo-7-(tosyloxy)-4H-chromen-2-yl)-1,2-phenylene diacetate
  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