| 1470083-57-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 噻吩并嘧啶酮衍生物
• CAS: 1470083-57-8
• 化学式: C₁₄H₁₇BrN₄O₃S
• 分子量: 401.284
• InChiKey: MGWNRYYNSVWYRA-MRVPVSSYSA-N

反应信息

• 作为反应物：
  描述：

  、 3-吡啶硼酸 在 四(三苯基膦)钯 、 碳酸氢钠 作用下， 以 乙二醇二甲醚 、 水 为溶剂， 以30%的产率得到1-ethyl-3-[7-methyl-6-(3-pyridyl)-5-[(3R)-tetrahydrofuran-3-yl]oxy-thiazolo[5,4-b]pyridin-2-yl]urea
  参考文献：
  名称：

  Thiazolopyridine Ureas as Novel Antitubercular Agents Acting through Inhibition of DNA Gyrase B

  摘要：

  A pharmacophore-based search led to the identification of thiazolopyridine ureas as a novel scaffold with antitubercular activity acting through inhibition of DNA Gyrase B (GyrB) ATPase. Evaluation of the binding mode of thiazolopyridines in a Mycobacterium tuberculosis (Mtb) GyrB homology model prompted exploration of the side chains at the thiazolopyridine ring C-5 position to access the ribose/solvent pocket. Potent compounds with GyrB IC50 ≤ 1 nM and Mtb MIC ≤ 0.1 μM were obtained with certain combinations of side chains at the C-5 position and heterocycles at the C-6 position of the thiazolopyridine core. Substitutions at C-5 also enabled optimization of the physicochemical properties. Representative compounds were cocrystallized with Streptococcus pneumoniae (Spn) ParE; these confirmed the binding modes predicted by the homology model. The target link to GyrB was confirmed by genetic mapping of the mutations conferring resistance to thiazolopyridine ureas. The compounds are bactericidal in vitro and efficacious in vivo in an acute murine model of tuberculosis.

  DOI：

  10.1021/jm401268f