5-hydroxy-3-(4-methoxyphenyl)-7-(4-nitrobenzyloxy)-chromen-4-one | 1173791-07-5

• 分子结构分类: 有机化合物 - 苯丙烷和聚酮 - 异黄酮类化合物
• 英文名称: 5-hydroxy-3-(4-methoxyphenyl)-7-(4-nitrobenzyloxy)-chromen-4-one
• 英文别名: 5-Hydroxy-3-(4-methoxyphenyl)-7-[(4-nitrophenyl)methoxy]chromen-4-one
• CAS: 1173791-07-5
• 化学式: C₂₃H₁₇NO₇
• 分子量: 419.39
• InChiKey: BVEKTSFYGPYCTQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.6
• 重原子数：
  31
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.09
• 拓扑面积：
  111
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  鹰嘴豆芽素A 、 对硝基溴化苄 在 potassium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以75%的产率得到5-hydroxy-3-(4-methoxyphenyl)-7-(4-nitrobenzyloxy)-chromen-4-one
  参考文献：
  名称：

  Synthesis of potential prodrug systems for reductive activation. Prodrugs for anti-angiogenic isoflavones and VEGF receptor tyrosine kinase inhibitory oxindoles

  摘要：

  A number of potential prodrug systems for reductive activation have been investigated. The prodrug systems chosen for the study were the 2-nitrophenylacetyl, 3-methyl-3-(3,6-dimethyl-1,4-benzoquinon-2-yl)butanoyl and 4-nitrobenzyl groups, readily attached to acidic OH or NH groups in drug molecules, and released upon bioreductive activation. The drug molecules studied were the naturally occurring isoflavone biochanin A, an inhibitor of VEGF-induced angiogenesis, and the pyrrolylmethylidenyl oxindole SU5416 (semaxanib) and its 6-hydroxy derivative, inhibitors of VEGF receptor tyrosine kinase. Following coupling the prodrug system to the drug, the compounds were evaluated chemically and biologically. Under chemical reducing conditions, the 3-methyl-3-(3,6-dimethyl-1,4-benzoquinon-2-yl)butanoic acid based prodrugs appear to fragment the most efficiently, followed by the 2-nitrophenylacetate esters with the 4-nitrobenzyl ethers being the least efficient. The potentially pro-anti-angiogenic compounds were also assayed for their ability to block VEGF-induced angiogenesis in HUVECS in comparison to the free agents. Control compounds that cannot be activated under bioreductive conditions are less potent than the free drug, whereas many of the potential prodrugs not only exhibit a dose response, but appear at least equipotent with the free drug. (C) 2009 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2009.04.014

文献信息

• Synthesis of potential prodrug systems for reductive activation. Prodrugs for anti-angiogenic isoflavones and VEGF receptor tyrosine kinase inhibitory oxindoles
  作者：Emilie A. Blanche、Lesley Maskell、Marie A. Colucci、Jacqueline L. Whatmore、Christopher J. Moody

  DOI：10.1016/j.tet.2009.04.014

  日期：2009.6

  A number of potential prodrug systems for reductive activation have been investigated. The prodrug systems chosen for the study were the 2-nitrophenylacetyl, 3-methyl-3-(3,6-dimethyl-1,4-benzoquinon-2-yl)butanoyl and 4-nitrobenzyl groups, readily attached to acidic OH or NH groups in drug molecules, and released upon bioreductive activation. The drug molecules studied were the naturally occurring isoflavone biochanin A, an inhibitor of VEGF-induced angiogenesis, and the pyrrolylmethylidenyl oxindole SU5416 (semaxanib) and its 6-hydroxy derivative, inhibitors of VEGF receptor tyrosine kinase. Following coupling the prodrug system to the drug, the compounds were evaluated chemically and biologically. Under chemical reducing conditions, the 3-methyl-3-(3,6-dimethyl-1,4-benzoquinon-2-yl)butanoic acid based prodrugs appear to fragment the most efficiently, followed by the 2-nitrophenylacetate esters with the 4-nitrobenzyl ethers being the least efficient. The potentially pro-anti-angiogenic compounds were also assayed for their ability to block VEGF-induced angiogenesis in HUVECS in comparison to the free agents. Control compounds that cannot be activated under bioreductive conditions are less potent than the free drug, whereas many of the potential prodrugs not only exhibit a dose response, but appear at least equipotent with the free drug. (C) 2009 Elsevier Ltd. All rights reserved.