[3-[3-[4-[4-[[5-(3,7-Dihydroxy-5-methoxy-4-oxochromen-2-yl)-2-hydroxyphenoxy]methyl]triazol-1-yl]butyl]-4-oxoquinazolin-2-yl]-5-hydroxyphenyl] acetate | 1427579-83-6

• 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: [3-[3-[4-[4-[[5-(3,7-Dihydroxy-5-methoxy-4-oxochromen-2-yl)-2-hydroxyphenoxy]methyl]triazol-1-yl]butyl]-4-oxoquinazolin-2-yl]-5-hydroxyphenyl] acetate
• CAS: 1427579-83-6
• 化学式: C₃₉H₃₃N₅O₁₁
• 分子量: 747.718
• InChiKey: DHJHMGWZUGDFQO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  55
• 可旋转键数：
  13
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.18
• 拓扑面积：
  215
• 氢给体数：
  4
• 氢受体数：
  14

反应信息

• 作为反应物：
  描述：

  [3-[3-[4-[4-[[5-(3,7-Dihydroxy-5-methoxy-4-oxochromen-2-yl)-2-hydroxyphenoxy]methyl]triazol-1-yl]butyl]-4-oxoquinazolin-2-yl]-5-hydroxyphenyl] acetate 在 三甲基铵三氧化硫共聚物 、 三乙胺 作用下， 以 乙腈 为溶剂， 反应 0.5h， 生成
  参考文献：
  名称：

  Discovery of Allosteric Modulators of Factor XIa by Targeting Hydrophobic Domains Adjacent to Its Heparin-Binding Site

  摘要：

  To discover promising sulfated allosteric modulators (SAMs) of glycosaminoglycan-binding proteins (GBPs), such as human factor XIa (FXIa), we screened a library of 26 synthetic, sulfated quinazolin-4(3H)-ones (QAOs) resulting in the identification of six molecules that reduced the V-max of substrate hydrolysis without influencing the K-M. Mutagenesis of residues of the heparin-binding site (HBS) of FXIa introduced a nearly 5-fold loss in inhibition potency supporting recognition of an allosteric site. Fluorescence studies showed a sigmoidal binding profile indicating highly cooperative binding. Competition with a positively charged, heparin-binding polymer did not fully nullify inhibition suggesting importance of hydrophobic forces to binding. This discovery suggests the operation of a dual-element recognition process, which relies on an initial Coulombic attraction of anionic SAMs to the cationic HBS of FXIa that forms a locked complex through tight interaction with an adjacent hydrophobic patch. The dual-element strategy may be widely applicable for discovering SAMs of other GBPs.

  DOI：

  10.1021/jm301757v
• 作为产物：
  描述：

  5-(4-oxo-3,4-dihydroquinazolin-2-yl)-1,3-phenylene diacetate 在 sodium azide 、 copper(ll) sulfate pentahydrate 、 potassium carbonate 、 sodium ascorbate 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 12.0h， 生成 [3-[3-[4-[4-[[5-(3,7-Dihydroxy-5-methoxy-4-oxochromen-2-yl)-2-hydroxyphenoxy]methyl]triazol-1-yl]butyl]-4-oxoquinazolin-2-yl]-5-hydroxyphenyl] acetate
  参考文献：
  名称：

  Discovery of Allosteric Modulators of Factor XIa by Targeting Hydrophobic Domains Adjacent to Its Heparin-Binding Site

  摘要：

  To discover promising sulfated allosteric modulators (SAMs) of glycosaminoglycan-binding proteins (GBPs), such as human factor XIa (FXIa), we screened a library of 26 synthetic, sulfated quinazolin-4(3H)-ones (QAOs) resulting in the identification of six molecules that reduced the V-max of substrate hydrolysis without influencing the K-M. Mutagenesis of residues of the heparin-binding site (HBS) of FXIa introduced a nearly 5-fold loss in inhibition potency supporting recognition of an allosteric site. Fluorescence studies showed a sigmoidal binding profile indicating highly cooperative binding. Competition with a positively charged, heparin-binding polymer did not fully nullify inhibition suggesting importance of hydrophobic forces to binding. This discovery suggests the operation of a dual-element recognition process, which relies on an initial Coulombic attraction of anionic SAMs to the cationic HBS of FXIa that forms a locked complex through tight interaction with an adjacent hydrophobic patch. The dual-element strategy may be widely applicable for discovering SAMs of other GBPs.

  DOI：

  10.1021/jm301757v