| 1160908-43-9

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 异喹啉及其衍生物
• CAS: 1160908-43-9
• 化学式: C₂₄H₂₉NO₈
• 分子量: 459.496
• InChiKey: UANPAFDQZDQRFZ-KRWDZBQOSA-N

反应信息

• 作为反应物：
  描述：

  在 三溴化硼 、 三甲基铵三氧化硫共聚物 、 三乙胺 作用下， 以 二氯甲烷 为溶剂， 生成
  参考文献：
  名称：

  On designing non-saccharide, allosteric activators of antithrombin

  摘要：

  Antithrombin, a plasma glycoprotein serpin, requires conformational activation by heparin to induce an anticoagulant effect, which is mediated through accelerated factor Xa inhibition. Heparin, a highly charged polymer and an allosteric activator of the serpin, is associated with major adverse effects. To design better, but radically different activators of antithrombin from heparin, we utilized a pharmacophore-based approach. A tetrahydroisoquinoline-based scaffold was designed to mimic four critical anionic groups of the key trisaccharide DEF constituting the sequence-specific pentasaccharide DEFGH in heparin. Activator IAS(5) containing 5,6-disulfated tetrahydroisoquinoline and 3,4,5-trisulfated phenyl rings was found to bind antithrombin at pH 7.4 with an affinity comparable to the reference trisaccharide DEF. IAS5 activated the inhibitor nearly 30-fold, nearly 2- to 3-fold higher than our first generation flavanoid-based designs. This work advances the concept of antithrombin activation through non-saccharide, organic molecules and pinpoints a direction for the design of more potent molecules. (C) 2008 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2008.09.042