ethyl 1-(4-methoxybenzyl)-6-(phenylamino)-1H-pyrazolo[3,4-b]pyridine-4-carboxylate | 1446114-13-1

• 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 1-(4-methoxybenzyl)-6-(phenylamino)-1H-pyrazolo[3,4-b]pyridine-4-carboxylate
• 英文别名: Ethyl 6-anilino-1-[(4-methoxyphenyl)methyl]pyrazolo[3,4-b]pyridine-4-carboxylate；ethyl 6-anilino-1-[(4-methoxyphenyl)methyl]pyrazolo[3,4-b]pyridine-4-carboxylate
• CAS: 1446114-13-1
• 化学式: C₂₃H₂₂N₄O₃
• 分子量: 402.453
• InChiKey: ZRSOZTYFHOFCGO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.5
• 重原子数：
  30
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  78.3
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  ethyl 1-(4-methoxybenzyl)-6-(phenylamino)-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 3.0h， 以69%的产率得到6-Anilino-1-[(4-methoxyphenyl)methyl]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：

  3-{N'-[1-(4-Methoxy-phenyl)-meth-(E)-ylidene]-hydrazino}-propionitrile 在 2,6-二叔丁基-4-甲基吡啶 、 palladium diacetate 、 caesium carbonate 、 溶剂黄146 、 sodium butanolate 、 S-1,1'-联-2-萘酚 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 正丁醇 、 苯 为溶剂， 反应 52.0h， 生成 ethyl 1-(4-methoxybenzyl)-6-(phenylamino)-1H-pyrazolo[3,4-b]pyridine-4-carboxylate
  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