1'-isopropyl-5'-nitro-2'-oxo-1',2'-dihydro-[3,3'-bipyridine]-5-carbonitrile | 1588768-52-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡啶及其衍生物
• 英文名称: 1'-isopropyl-5'-nitro-2'-oxo-1',2'-dihydro-[3,3'-bipyridine]-5-carbonitrile
• CAS: 1588768-52-8
• 化学式: C₁₄H₁₂N₄O₃
• 分子量: 284.274
• InChiKey: WMUOIPXWFVYLOL-UHFFFAOYSA-N

物化性质

• 沸点：
  477.3±45.0 °C(predicted)
• 密度：
  1.36±0.1 g/cm3(Temp: 20 °C; Press: 760 Torr)(predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.27
• 重原子数：
  21.0
• 可旋转键数：
  3.0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  101.82
• 氢给体数：
  0.0
• 氢受体数：
  6.0

反应信息

• 作为反应物：
  描述：

  1'-isopropyl-5'-nitro-2'-oxo-1',2'-dihydro-[3,3'-bipyridine]-5-carbonitrile 在 palladium on activated charcoal 、 氢气 、 溴 、 二正丁基氧化锡 、 三乙胺 作用下， 以 乙醇 、 溶剂黄146 为溶剂， 10.0~110.0 ℃ 、275.8 kPa 条件下， 反应 0.5h， 生成 1-ethyl-3-(6-(5-cyanopyridin-3-yl)-4-isopropyl-5-oxo-4,5-dihydrothiazolo[5,4-b]pyridin-2-yl)urea
  参考文献：
  名称：

  Thiazolopyridone ureas as DNA gyrase B inhibitors: Optimization of antitubercular activity and efficacy

  摘要：

  Scaffold hopping from the thiazolopyridine ureas led to thiazolopyridone ureas with potent antitubercular activity acting through inhibition of DNA GyrB ATPase activity. Structural diversity was introduced, by extension of substituents from the thiazolopyridone N-4 position, to access hydrophobic interactions in the ribose pocket of the ATP binding region of GyrB. Further optimization of hydrogen bond interactions with arginines in site-2 of GyrB active site pocket led to potent inhibition of the enzyme (IC50 2 nM) along with potent cellular activity (MIC = 0.1 mu M) against Mycobacterium tuberculosis (Mtb). Efficacy was demonstrated in an acute mouse model of tuberculosis on oral administration. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.12.080
• 作为产物：
  描述：

  3-溴-5-硝基-2-羟基吡啶 在 碳酸氢钠 、 sodium carbonate 作用下， 以 乙二醇二甲醚 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 0.25h， 生成 1'-isopropyl-5'-nitro-2'-oxo-1',2'-dihydro-[3,3'-bipyridine]-5-carbonitrile
  参考文献：
  名称：

  Thiazolopyridone ureas as DNA gyrase B inhibitors: Optimization of antitubercular activity and efficacy

  摘要：

  Scaffold hopping from the thiazolopyridine ureas led to thiazolopyridone ureas with potent antitubercular activity acting through inhibition of DNA GyrB ATPase activity. Structural diversity was introduced, by extension of substituents from the thiazolopyridone N-4 position, to access hydrophobic interactions in the ribose pocket of the ATP binding region of GyrB. Further optimization of hydrogen bond interactions with arginines in site-2 of GyrB active site pocket led to potent inhibition of the enzyme (IC50 2 nM) along with potent cellular activity (MIC = 0.1 mu M) against Mycobacterium tuberculosis (Mtb). Efficacy was demonstrated in an acute mouse model of tuberculosis on oral administration. (C) 2014 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmcl.2013.12.080