| 1384120-21-1

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 苯并三唑类
• CAS: 1384120-21-1
• 化学式: C₉H₇N₃S₂
• 分子量: 221.307
• InChiKey: YTXRMWVLBRWWOC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.54
• 重原子数：
  14.0
• 可旋转键数：
  0.0
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  30.19
• 氢给体数：
  1.0
• 氢受体数：
  5.0

反应信息

• 作为反应物：
  描述：

  、 (E)-3-甲氧基-2-(2-溴甲基苯基)丙烯酸甲酯 在 sodium hydroxide 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 以45%的产率得到methyl (E)-3-methoxy-2-[2-[(8-methyl-[1,2,4]triazolo[3,4-b][1,3]benzothiazol-6-yl)sulfanylmethyl]phenyl]prop-2-enoate
  参考文献：
  名称：

  Computational Discovery of Picomolar Q_o Site Inhibitors of Cytochrome bc₁ Complex

  摘要：

  A critical challenge to the fragment-based drug discovery (FBDD) is its low-throughput nature due to the necessity of biophysical method-based fragment screening. Herein, a method of pharmacophore-linked fragment virtual screening (PFVS) was successfully developed. Its application yielded the first picomolar-range Q(o) site inhibitors of the cytochrome bc(1) complex, an important membrane protein for drug and fungicide discovery. Compared with the original hit compound 4 (K-i = 881.80 nM, porcine bc(1)), the most potent compound 4f displayed 20 507-fold improved binding affinity (K-i = 43.00 pM). Compound 4f was proved to be a noncompetitive inhibitor with respect to the substrate cytochrome c, but a competitive inhibitor with respect to the substrate ubiquinol. Additionally, we determined the crystal structure of compound 4e (K-i = 83.00 pM) bound to the chicken bc(1) at 2.70 angstrom resolution, providing a molecular basis for understanding its ultrapotency. To our knowledge, this study is the first application of the FBDD method in the discovery of picomolar inhibitors of a membrane protein. This work demonstrates that the novel PFVS approach is a high-throughput drug discovery method, independent of biophysical screening techniques.

  DOI：

  10.1021/ja3001908