Sodium;[3-[3-[4-[4-[[2-(3-acetyloxyphenyl)-4-oxoquinazolin-3-yl]methyl]triazol-1-yl]butyl]-4-oxoquinazolin-2-yl]phenyl] sulfate | 1427579-47-2

• 分子结构分类: 有机化合物
• 英文名称: Sodium;[3-[3-[4-[4-[[2-(3-acetyloxyphenyl)-4-oxoquinazolin-3-yl]methyl]triazol-1-yl]butyl]-4-oxoquinazolin-2-yl]phenyl] sulfate
• CAS: 1427579-47-2
• 化学式: C₃₇H₃₀N₇O₈S*Na
• 分子量: 755.743
• InChiKey: KGLFATWCEZYAIV-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  1.33
• 重原子数：
  54
• 可旋转键数：
  13
• 环数：
  7.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  197
• 氢给体数：
  0
• 氢受体数：
  12

反应信息

• 作为产物：
  描述：

  [3-[3-[[1-[4-[2-(3-Hydroxyphenyl)-4-oxoquinazolin-3-yl]butyl]triazol-4-yl]methyl]-4-oxoquinazolin-2-yl]phenyl] 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 Sodium;[3-[3-[4-[4-[[2-(3-acetyloxyphenyl)-4-oxoquinazolin-3-yl]methyl]triazol-1-yl]butyl]-4-oxoquinazolin-2-yl]phenyl] sulfate
  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