5-hydroxy-2-(4-hydroxyphenyl)-4-oxo-4H-chromen-7-yl-4-methylbenzenesulfonate | 1104802-77-8

• 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: 5-hydroxy-2-(4-hydroxyphenyl)-4-oxo-4H-chromen-7-yl-4-methylbenzenesulfonate
• 英文别名: 7-O-tosylapigenin；[5-Hydroxy-2-(4-hydroxyphenyl)-4-oxochromen-7-yl] 4-methylbenzenesulfonate
• CAS: 1104802-77-8
• 化学式: C₂₂H₁₆O₇S
• 分子量: 424.431
• InChiKey: TUEDYMXRPFBUFP-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  30
• 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：
  119
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  5-hydroxy-2-(4-hydroxyphenyl)-4-oxo-4H-chromen-7-yl-4-methylbenzenesulfonate 在 10% Pd(OH)2/C 、 氢气 、 palladium diacetate 、 potassium carbonate 、 caesium carbonate 、 2-二环己基磷-2,4,6-三异丙基联苯 作用下， 以 1,4-二氧六环 、 甲醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 15.0h， 生成 5-hydroxy-2-(4-hydroxyphenyl)-7-morpholino-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：

  [7-乙酰氧基-2-(4-乙酰氧基苯基)-4-氧代苯并吡喃-5-基]乙酸酯 在 咪唑 、 氨 、 苯硫酚 、 三乙胺 作用下， 以 四氢呋喃 、 N-甲基吡咯烷酮 、 甲醇 为溶剂， 反应 12.0h， 生成 5-hydroxy-2-(4-hydroxyphenyl)-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

文献信息

• Synthesis of Oriented Anti-Virus 7-O-Substituted Apigenins
  作者：Kumi Yoshida、Kin-ichi Oyama、Tadao Kondo

  DOI：10.3987/com-08-s(n)79

  日期：——