5,5′-((1,4-phenylenebis(methylene))bis(oxy))bis(2-(3,4-dihydroxyphenyl)-3,7-dihydroxy-4H-chromen-4-one)

• 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: 5,5′-((1,4-phenylenebis(methylene))bis(oxy))bis(2-(3,4-dihydroxyphenyl)-3,7-dihydroxy-4H-chromen-4-one)
• 英文别名: 2-(3,4-Dihydroxyphenyl)-5-[[4-[[2-(3,4-dihydroxyphenyl)-3,7-dihydroxy-4-oxochromen-5-yl]oxymethyl]phenyl]methoxy]-3,7-dihydroxychromen-4-one；2-(3,4-dihydroxyphenyl)-5-[[4-[[2-(3,4-dihydroxyphenyl)-3,7-dihydroxy-4-oxochromen-5-yl]oxymethyl]phenyl]methoxy]-3,7-dihydroxychromen-4-one
• 化学式: C₃₈H₂₆O₁₄
• 分子量: 706.616
• InChiKey: UTWPNYOWYYTWNI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.9
• 重原子数：
  52
• 可旋转键数：
  8
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.05
• 拓扑面积：
  233
• 氢给体数：
  8
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  5,5′-((1,4-phenylenebis(methylene))bis(oxy))bis(2-(3,4-dihydroxyphenyl)-3,7-dihydroxy-4H-chromen-4-one) 在 三甲基铵三氧化硫共聚物 、 三乙胺 作用下， 以 乙腈 为溶剂， 生成 octasodium 4-(5-((4-(((2-(3,4-bis(sulfonatooxy)phenyl)-4-oxo-3,7-bis(sulfonatooxy)-4H-chromen-5-yl)oxy)methyl)benzyl)oxy)-4-oxo-3,7-bis(sulfonatooxy)-4H-chromen-2-yl)-1,2-phenylene bis(sulfate)
  参考文献：
  名称：

  Potent, Selective, Allosteric Inhibition of Human Plasmin by Sulfated Non-Saccharide Glycosaminoglycan Mimetics

  摘要：

  Although plasmin inhibitors could be used in multiple disorders, their use has been restricted to preventing blood loss in hemostatic dysregulation because of poor efficacy and adverse effects of current agents. We reasoned that a new class of direct inhibitors that offer better efficacy, selectivity, and safety could be discovered by exploiting allosterism in plasmin, a protease homologous to other allosteric serine proteases. We report on the synthesis, biological activity, and mechanism of action of a group of small molecules, called non-saccharide glycosaminoglycan mimetics (NSGMs), as direct allosteric plasmin inhibitors. Our results show that distinct NSGMs selectively inhibit human fall-length plasmin. The molecule inhibited clot lysis, alluding to its promise as an allosteric regulator of plasmin. We show that direct allosteric inhibition of plasmin could led to new antifibrinolytic agent(s) that may exhibit better efficacy, potency, selectivity, and safety in comparison to current therapy.

  DOI：

  10.1021/acs.jmedchem.6b01474
• 作为产物：
  描述：

  槲皮素 在 三甲基溴硅烷 、 potassium carbonate 、 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 27.03h， 生成 5,5′-((1,4-phenylenebis(methylene))bis(oxy))bis(2-(3,4-dihydroxyphenyl)-3,7-dihydroxy-4H-chromen-4-one)
  参考文献：
  名称：

  Potent, Selective, Allosteric Inhibition of Human Plasmin by Sulfated Non-Saccharide Glycosaminoglycan Mimetics

  摘要：

  Although plasmin inhibitors could be used in multiple disorders, their use has been restricted to preventing blood loss in hemostatic dysregulation because of poor efficacy and adverse effects of current agents. We reasoned that a new class of direct inhibitors that offer better efficacy, selectivity, and safety could be discovered by exploiting allosterism in plasmin, a protease homologous to other allosteric serine proteases. We report on the synthesis, biological activity, and mechanism of action of a group of small molecules, called non-saccharide glycosaminoglycan mimetics (NSGMs), as direct allosteric plasmin inhibitors. Our results show that distinct NSGMs selectively inhibit human fall-length plasmin. The molecule inhibited clot lysis, alluding to its promise as an allosteric regulator of plasmin. We show that direct allosteric inhibition of plasmin could led to new antifibrinolytic agent(s) that may exhibit better efficacy, potency, selectivity, and safety in comparison to current therapy.

  DOI：

  10.1021/acs.jmedchem.6b01474