ethyl 6-(phenyl)ethynyl-1-(pyridin-4-yl)methyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylate | 1227077-06-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡唑并吡啶类
• 英文名称: ethyl 6-(phenyl)ethynyl-1-(pyridin-4-yl)methyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylate
• 英文别名: Ethyl 6-(2-phenylethynyl)-1-(pyridin-4-ylmethyl)pyrazolo[3,4-b]pyridine-4-carboxylate；ethyl 6-(2-phenylethynyl)-1-(pyridin-4-ylmethyl)pyrazolo[3,4-b]pyridine-4-carboxylate
• CAS: 1227077-06-6
• 化学式: C₂₃H₁₈N₄O₂
• 分子量: 382.422
• InChiKey: QBTRDIIGFKAULO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.6
• 重原子数：
  29
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.13
• 拓扑面积：
  69.9
• 氢给体数：
  0
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  ethyl 6-(phenyl)ethynyl-1-(pyridin-4-yl)methyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylate 在 sodium hydroxide 、 盐酸 作用下， 以 四氢呋喃 、 水 为溶剂， 反应 4.0h， 以65%的产率得到6-(2-Phenylethynyl)-1-(pyridin-4-ylmethyl)pyrazolo[3,4-b]pyridine-4-carboxylic acid
  参考文献：
  名称：

  Non-Nucleoside Inhibitors of BasE, an Adenylating Enzyme in the Siderophore Biosynthetic Pathway of the Opportunistic PathogenAcinetobacter baumannii

  摘要：

  Siderophores are small-molecule iron chelators produced by bacteria and other microorganisms for survival under iron limiting conditions such as found in a mammalian host. Siderophore biosynthesis is essential for the virulence of many important Gram-negative pathogens including Acinetobacter baumannii, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Escherichia coli. We performed high-throughput screening against BasE, which is involved in siderophore biosynthesis in A. baumannii, and identified 6-phenyl-1-(pyridin-4-ylmethyl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid 15. Herein we report the synthesis, biochemical, and microbiological evaluation of a systematic series of analogues of the HTS hit 15. Analogue 67 is the most potent analogue with a K-D of 2 nM against BasE. Structural characterization of the inhibitors with BasE reveals that they bind in a unique orientation in the active site, occupying all three substrate binding sites, and thus can be considered as multisubstrate inhibitors. These results provide a foundation for future studies aimed at increasing both enzyme potency and antibacterial activity.

  DOI：

  10.1021/jm301709s
• 作为产物：
  描述：

  ethyl 6-oxo-1-(pyridin-4-ylmethyl)-6,7-dihydro-1H-pyrazolo[3,4-b]pyridine-4-carboxylate 、 苯乙炔 在 三乙胺 、 bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate 、 双(乙腈)氯化钯(II) 、 caesium carbonate 、 2-(二环己基膦基)联苯 作用下， 以 1,4-二氧六环 为溶剂， 反应 2.0h， 以87%的产率得到ethyl 6-(phenyl)ethynyl-1-(pyridin-4-yl)methyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylate
  参考文献：
  名称：

  Efficient Pd-Catalyzed Coupling of Tautomerizable Heterocycles with Terminal Alkynes via C−OH Bond Activation Using PyBrOP

  摘要：

  The direct alkynylation of tautomerizable heterocycles is described via a two-step process involving in situ C OH activation with bromotripyrrolidinophosphonium hexafluorophosphate (PyBrOP) followed by Sonogashira coupling with a wide range of alkyl or aryl terminal alkynes using a copper-free system employing PdCl2(CH3CN)(2) and 2-(dicyclohexylphosphino)biphenyl.

  DOI：

  10.1021/ol100657n