| 1443016-05-4

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• CAS: 1443016-05-4
• 化学式: C₅₈H₆₄O₂₀Si
• 分子量: 1109.22
• InChiKey: CJXMYLGWNHGJLM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  12.84
• 重原子数：
  79.0
• 可旋转键数：
  23.0
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  231.6
• 氢给体数：
  0.0
• 氢受体数：
  20.0

反应信息

• 作为反应物：
  描述：

  在 potassium fluoride 、 溶剂黄146 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 以90%的产率得到
  参考文献：
  名称：

  Designing Allosteric Regulators of Thrombin. Exosite 2 Features Multiple Subsites That Can Be Targeted by Sulfated Small Molecules for Inducing Inhibition

  摘要：

  We recently designed a group of novel exosite-2-directed sulfated, small, allosteric inhibitors of thrombin. To develop more potent inhibitors, monosulfated benzofuran tri- and tetrameric homologues of the parent designed dimers were synthesized in seven to eight steps and found to exhibit a wide range of potencies. Among these, trimer 9a was found to be nearly 10-fold more potent than the first generation molecules. Michaelis-Menten studies indicated an allosteric mechanism of inhibition. Competitive studies using a hirudin peptide (exosite 1 ligand) and unfractionated heparin, heparin octasaccharide, and gamma'-fibrinogen peptide (exosite 2 ligands) demonstrated exosite 2 recognition in a manner different from that of the parent dimers. Alanine scanning mutagenesis of 12 Arg/Lys residues of exosite 2 revealed a defect in 9a potency for Arg233Ala thrombin only confirming the major difference in site of recognition between the two structurally related sulfated benzofurans. The results suggest that multiple avenues are available within exosite 2 for inducing thrombin inhibition.

  DOI：

  10.1021/jm400369q
• 作为产物：
  描述：

  Ethyl 5-[tert-butyl(dimethyl)silyl]oxy-6-methoxy-2-methyl-1-benzofuran-3-carboxylate 在 N-溴代丁二酰亚胺(NBS) 、 caesium carbonate 、 N,N-二甲基甲酰胺 作用下， 以 乙酸乙酯 为溶剂， 反应 2.33h， 生成
  参考文献：
  名称：

  Designing Allosteric Regulators of Thrombin. Exosite 2 Features Multiple Subsites That Can Be Targeted by Sulfated Small Molecules for Inducing Inhibition

  摘要：

  We recently designed a group of novel exosite-2-directed sulfated, small, allosteric inhibitors of thrombin. To develop more potent inhibitors, monosulfated benzofuran tri- and tetrameric homologues of the parent designed dimers were synthesized in seven to eight steps and found to exhibit a wide range of potencies. Among these, trimer 9a was found to be nearly 10-fold more potent than the first generation molecules. Michaelis-Menten studies indicated an allosteric mechanism of inhibition. Competitive studies using a hirudin peptide (exosite 1 ligand) and unfractionated heparin, heparin octasaccharide, and gamma'-fibrinogen peptide (exosite 2 ligands) demonstrated exosite 2 recognition in a manner different from that of the parent dimers. Alanine scanning mutagenesis of 12 Arg/Lys residues of exosite 2 revealed a defect in 9a potency for Arg233Ala thrombin only confirming the major difference in site of recognition between the two structurally related sulfated benzofurans. The results suggest that multiple avenues are available within exosite 2 for inducing thrombin inhibition.

  DOI：

  10.1021/jm400369q