Sodium;[3-ethoxycarbonyl-2-[[3-ethoxycarbonyl-2-[[3-ethoxycarbonyl-2-[(3-ethoxycarbonyl-6-methoxy-2-methyl-1-benzofuran-5-yl)oxymethyl]-6-methoxy-1-benzofuran-5-yl]oxymethyl]-6-methoxy-1-benzofuran-5-yl]oxymethyl]-6-methoxy-1-benzofuran-5-yl] sulfate | 1443016-07-6

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机硫酸及其衍生物
• 英文名称: Sodium;[3-ethoxycarbonyl-2-[[3-ethoxycarbonyl-2-[[3-ethoxycarbonyl-2-[(3-ethoxycarbonyl-6-methoxy-2-methyl-1-benzofuran-5-yl)oxymethyl]-6-methoxy-1-benzofuran-5-yl]oxymethyl]-6-methoxy-1-benzofuran-5-yl]oxymethyl]-6-methoxy-1-benzofuran-5-yl] sulfate
• 英文别名: sodium;[3-ethoxycarbonyl-2-[[3-ethoxycarbonyl-2-[[3-ethoxycarbonyl-2-[(3-ethoxycarbonyl-6-methoxy-2-methyl-1-benzofuran-5-yl)oxymethyl]-6-methoxy-1-benzofuran-5-yl]oxymethyl]-6-methoxy-1-benzofuran-5-yl]oxymethyl]-6-methoxy-1-benzofuran-5-yl] sulfate
• CAS: 1443016-07-6
• 化学式: C₅₂H₄₉O₂₃S*Na
• 分子量: 1097.0
• InChiKey: XKLQGZXYDYVQSK-UHFFFAOYSA-M

计算性质

• 辛醇/水分配系数(LogP)：
  6.3
• 重原子数：
  77
• 可旋转键数：
  27
• 环数：
  8.0
• sp3杂化的碳原子比例：
  0.31
• 拓扑面积：
  297
• 氢给体数：
  0
• 氢受体数：
  23

反应信息

• 作为产物：
  描述：

  Ethyl 5-[[5-[[5-[tert-butyl(dimethyl)silyl]oxy-3-ethoxycarbonyl-6-methoxy-1-benzofuran-2-yl]methoxy]-3-ethoxycarbonyl-6-methoxy-1-benzofuran-2-yl]methoxy]-6-methoxy-2-methyl-1-benzofuran-3-carboxylate 在 potassium fluoride 、 三甲基铵三氧化硫共聚物 、 caesium carbonate 、 溶剂黄146 、 三乙胺 、 N,N-二甲基甲酰胺 作用下， 以 乙酸乙酯 、 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 12.0h， 生成 Sodium;[3-ethoxycarbonyl-2-[[3-ethoxycarbonyl-2-[[3-ethoxycarbonyl-2-[(3-ethoxycarbonyl-6-methoxy-2-methyl-1-benzofuran-5-yl)oxymethyl]-6-methoxy-1-benzofuran-5-yl]oxymethyl]-6-methoxy-1-benzofuran-5-yl]oxymethyl]-6-methoxy-1-benzofuran-5-yl] sulfate
  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

文献信息

• Designing Allosteric Regulators of Thrombin. Exosite 2 Features Multiple Subsites That Can Be Targeted by Sulfated Small Molecules for Inducing Inhibition
  作者：Preetpal Singh Sidhu、May H. Abdel Aziz、Aurijit Sarkar、Akul Y. Mehta、Qibing Zhou、Umesh R. Desai

  DOI：10.1021/jm400369q

  日期：2013.6.27

  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.