(5-((tert-butyldimethylsilyl)oxy)-6-methoxy-2-methylbenzofuran-3-yl)methanol | 1186532-75-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并呋喃
• 英文名称: (5-((tert-butyldimethylsilyl)oxy)-6-methoxy-2-methylbenzofuran-3-yl)methanol
• CAS: 1186532-75-1
• 化学式: C₁₇H₂₆O₄Si
• 分子量: 322.477
• InChiKey: PSICRYZVAUNWLS-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.63
• 重原子数：
  22.0
• 可旋转键数：
  4.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.53
• 拓扑面积：
  51.83
• 氢给体数：
  1.0
• 氢受体数：
  4.0

反应信息

• 作为反应物：
  描述：

  (5-((tert-butyldimethylsilyl)oxy)-6-methoxy-2-methylbenzofuran-3-yl)methanol 在 三甲基铵三氧化硫共聚物 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 0.67h， 生成
  参考文献：
  名称：

  Rational Design of Potent, Small, Synthetic Allosteric Inhibitors of Thrombin

  摘要：

  Thrombin is a key enzyme targeted by the majority of current anticoagulants that are direct inhibitors. Allosteric inhibition of thrombin may. offer a major advantage of finely tuned regulation. We present here sulfated benzofurans as the first examples of potent, small allosteric inhibitors of thrombin. A sulfated benzofuran library of 15 sulfated monomers and 13 sulfated dimers with different charged, polar, and hydrophobic substituents was studied in this work. Synthesis of the sulfated benzofurans was achieved through a multiple step, highly branched strategy, which culminated with microwave-assisted chemical sulfation. Of the 28 potential inhibitors, 11 exhibited reasonable inhibition of human a.-thrombin at pH 7.4. Structure-activity relationship analysis indicated that sulfation at the 5-position of the benzofuran scaffold was essential for targeting thrombin. A tert-butyl 5-sulfated benzofuran derivative was found to be the most potent thrombin inhibitor with an IC50 of 7.3 mu M under physiologically relevant conditions. Michaelis-Menten studies showed an allosteric inhibition phenomenon. Plasma clotting assays indicate that the sulfated benzofurans prolong both the activated partial thromboplastin time and prothrombin time. Overall, this work puts forward sulfated benzofurans as the first small, synthetic molecules as powerful lead compounds for the design of a new class of allosteric inhibitors of thrombin.

  DOI：

  10.1021/jm2005767
• 作为产物：
  描述：

  ethyl 5,6-dihydroxy-2-methylbenzofuran-3-carboxylate 在 咪唑 、 lithium aluminium tetrahydride 、 caesium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 35.0h， 生成 (5-((tert-butyldimethylsilyl)oxy)-6-methoxy-2-methylbenzofuran-3-yl)methanol
  参考文献：
  名称：

  Rational Design of Potent, Small, Synthetic Allosteric Inhibitors of Thrombin

  摘要：

  Thrombin is a key enzyme targeted by the majority of current anticoagulants that are direct inhibitors. Allosteric inhibition of thrombin may. offer a major advantage of finely tuned regulation. We present here sulfated benzofurans as the first examples of potent, small allosteric inhibitors of thrombin. A sulfated benzofuran library of 15 sulfated monomers and 13 sulfated dimers with different charged, polar, and hydrophobic substituents was studied in this work. Synthesis of the sulfated benzofurans was achieved through a multiple step, highly branched strategy, which culminated with microwave-assisted chemical sulfation. Of the 28 potential inhibitors, 11 exhibited reasonable inhibition of human a.-thrombin at pH 7.4. Structure-activity relationship analysis indicated that sulfation at the 5-position of the benzofuran scaffold was essential for targeting thrombin. A tert-butyl 5-sulfated benzofuran derivative was found to be the most potent thrombin inhibitor with an IC50 of 7.3 mu M under physiologically relevant conditions. Michaelis-Menten studies showed an allosteric inhibition phenomenon. Plasma clotting assays indicate that the sulfated benzofurans prolong both the activated partial thromboplastin time and prothrombin time. Overall, this work puts forward sulfated benzofurans as the first small, synthetic molecules as powerful lead compounds for the design of a new class of allosteric inhibitors of thrombin.

  DOI：

  10.1021/jm2005767

文献信息

• First steps in the direction of synthetic, allosteric, direct inhibitors of thrombin and factor Xa
  作者：Jenson Verghese、Aiye Liang、Preet Pal Singh Sidhu、Michael Hindle、Qibing Zhou、Umesh R. Desai

  DOI：10.1016/j.bmcl.2009.06.013

  日期：2009.8

  Designing non-saccharide functional mimics of heparin is a major challenge. In this work, a library of small, aromatic molecules based on the sulfated DHP scaffold was synthesized and screened against thrombin and factor Xa. The results reveal that (i) selected monomeric benzofuran derivatives inhibit the two enzymes, albeit weakly; (ii) the two enzymes recognize different structural features in the

  设计肝素的非糖类功能模拟物是一项重大挑战。在这项工作中，合成了一个基于硫酸化 DHP 支架的芳香小分子库，并针对凝血酶和 Xa 因子进行了筛选。结果表明：（ⅰ）选择的单体苯并呋喃衍生物抑制这两种酶，尽管弱; (ii) 这两种酶识别所研究的苯并呋喃中的不同结构特征，表明识别具有显着的选择性；(iii) 抑制机制是变构的。这些分子代表了两种酶的第一个变构小分子抑制剂。