6-[4-(2-nitroimidazol-1-ylmethyl)-1,2,3-triazol-1-yl]-3',4'-dihydroxyflavonol | 1332713-47-9

• 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: 6-[4-(2-nitroimidazol-1-ylmethyl)-1,2,3-triazol-1-yl]-3',4'-dihydroxyflavonol
• 英文别名: 2-(3,4-Dihydroxyphenyl)-3-hydroxy-6-[4-[(2-nitroimidazol-1-yl)methyl]triazol-1-yl]chromen-4-one；2-(3,4-dihydroxyphenyl)-3-hydroxy-6-[4-[(2-nitroimidazol-1-yl)methyl]triazol-1-yl]chromen-4-one
• CAS: 1332713-47-9
• 化学式: C₂₁H₁₄N₆O₇
• 分子量: 462.378
• InChiKey: DZVMYGAQRJAAMQ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  34
• 可旋转键数：
  4
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  181
• 氢给体数：
  3
• 氢受体数：
  10

反应信息

• 作为产物：
  描述：

  5-氨基-2-羟基苯乙酮 在 茴香硫醚 、 硫酸 、 双氧水 、 copper(II) sulfate 、 sodium ascorbate 、 三氟乙酸 、 potassium hydroxide 、 sodium hydroxide 、 sodium nitrite 、 三[(1-苄基-1H-1,2,3-三唑-4-基)甲基]胺 作用下， 以 1,4-二氧六环 、 乙醇 、 水 、 二甲基亚砜 为溶剂， 反应 1.5h， 生成 6-[4-(2-nitroimidazol-1-ylmethyl)-1,2,3-triazol-1-yl]-3',4'-dihydroxyflavonol
  参考文献：
  名称：

  Synthesis of a hypoxia-targeted conjugate of the cardioprotective agent 3′,4′-dihydroxyflavonol and evaluation of its ability to reduce ischaemia/reperfusion injury

  摘要：

  3',4'-Dihydroxyflavonol (DiOHF) is a cardioprotective flavonol that reduces injury associated with myocardial ischaemia and reperfusion. We hypothesized that the efficacy of DiOHF could be enhanced through its targeting to hypoxic regions of partial reperfusion. Copper(I)-catalyzed ligation of an azide-modified DiOHF analogue to 2-propargyl-nitroimidazole afforded a DiOHF-nitroimidazole conjugate (DiOHF-NIm). When incubated with Con8 cells under normoxic conditions DiOHF-NIm could be detected in both the culture supernatant and cell lysate, whereas under hypoxic conditions it was present in substantially reduced amounts consistent with its selective metabolism under hypoxia. DiOHF-NIm possessed antioxidant activity comparable to DiOHF through scavenging of superoxide produced by NADPH/NADPH oxidase, but had significantly attenuated vasorelaxant activity. DiOHF-NIm treatment significantly reduced lactate dehydrogenase release following ischaemia/reperfusion in hindlimbs of anaesthetized rats (p < 0.05), to a level similar to DiOHF treatment but also at earlier time points. DiOHF-NIm significantly reduced levels of myeloperoxidase (p < 0.05), a biomarker of neutrophil accumulation, whereas the reduction afforded by DiOHF was not significant. DiOHF-NIm therefore represents a promising potential therapeutic for ischaemia/reperfusion injury. (c) 2011 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2011.03.040

文献信息

• Synthesis of a hypoxia-targeted conjugate of the cardioprotective agent 3′,4′-dihydroxyflavonol and evaluation of its ability to reduce ischaemia/reperfusion injury
  作者：Suwan Yap、Owen L. Woodman、Peter J. Crack、Spencer J. Williams

  DOI：10.1016/j.bmcl.2011.03.040

  日期：2011.9

  3',4'-Dihydroxyflavonol (DiOHF) is a cardioprotective flavonol that reduces injury associated with myocardial ischaemia and reperfusion. We hypothesized that the efficacy of DiOHF could be enhanced through its targeting to hypoxic regions of partial reperfusion. Copper(I)-catalyzed ligation of an azide-modified DiOHF analogue to 2-propargyl-nitroimidazole afforded a DiOHF-nitroimidazole conjugate (DiOHF-NIm). When incubated with Con8 cells under normoxic conditions DiOHF-NIm could be detected in both the culture supernatant and cell lysate, whereas under hypoxic conditions it was present in substantially reduced amounts consistent with its selective metabolism under hypoxia. DiOHF-NIm possessed antioxidant activity comparable to DiOHF through scavenging of superoxide produced by NADPH/NADPH oxidase, but had significantly attenuated vasorelaxant activity. DiOHF-NIm treatment significantly reduced lactate dehydrogenase release following ischaemia/reperfusion in hindlimbs of anaesthetized rats (p < 0.05), to a level similar to DiOHF treatment but also at earlier time points. DiOHF-NIm significantly reduced levels of myeloperoxidase (p < 0.05), a biomarker of neutrophil accumulation, whereas the reduction afforded by DiOHF was not significant. DiOHF-NIm therefore represents a promising potential therapeutic for ischaemia/reperfusion injury. (c) 2011 Elsevier Ltd. All rights reserved.