1-(pyridin-4-ylmethyl)-1H-pyrazol-5-amine | 202344-41-0

• 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-(pyridin-4-ylmethyl)-1H-pyrazol-5-amine
• 英文别名: 4-(Pyrazol-1-ylmethyl)pyridine
• CAS: 202344-41-0
• 化学式: C₉H₉N₃
• 分子量: 159.191
• InChiKey: RWZOGWBXJGNXIU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  12
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  30.7
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  1-(pyridin-4-ylmethyl)-1H-pyrazol-5-amine 在 溶剂黄146 、 三乙胺 、 bromo-tris(1-pyrrolidinyl)phosphonium hexafluorophosphate 作用下， 以 1,4-二氧六环 、 苯 为溶剂， 反应 25.0h， 生成 6-(1H-indol-5-yl)-1-(pyridin-4-ylmethyl)-1H-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-(2-(吡啶-4-基亚甲基)肼基)丙腈 在 sodium butanolate 作用下， 以 正丁醇 为溶剂， 以10.6 g的产率得到1-(pyridin-4-ylmethyl)-1H-pyrazol-5-amine
  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

文献信息

• Bhatti, Inayat A.; Busby, Reginald E.; Bin Mohamed, Murtedza, Journal of the Chemical Society. Perkin transactions I, 1997, # 24, p. 3581 - 3585
  作者：Bhatti, Inayat A.、Busby, Reginald E.、Bin Mohamed, Murtedza、Parrick, John、Shaw, C. J. Granville

  DOI：——

  日期：——
• SMALL MOLECULE MYRISTATE INHIBITORS OF BCR-ABL AND METHODS OF USE
  申请人：Dana Farber Cancer Institute

  公开号：EP2222162A2

  公开（公告）日：2010-09-01
• EP2545055B1
  申请人：——

  公开号：EP2545055B1

  公开（公告）日：2017-08-09
• [EN] SMALL MOLECULE MYRISTATE INHIBITORS OF BCR-ABL AND METHODS OF USE<br/>[FR] INHIBITEURS MYRISTATE À PETITES MOLÉCULES DE BCR-ABL ET PROCÉDÉS D'UTILISATION
  申请人：DANA FARBER CANCER INST INC

  公开号：WO2009073153A2

  公开（公告）日：2009-06-11

  The present invention provides novel heteroaryl compounds that are linked to an aryl group via an amine linker. Such compounds are useful for the treatment of cancers.
• Non-Nucleoside Inhibitors of BasE, an Adenylating Enzyme in the Siderophore Biosynthetic Pathway of the Opportunistic Pathogen<i>Acinetobacter baumannii</i>
  作者：João Neres、Curtis A. Engelhart、Eric J. Drake、Daniel J. Wilson、Peng Fu、Helena I. Boshoff、Clifton E. Barry、Andrew M. Gulick、Courtney C. Aldrich

  DOI：10.1021/jm301709s

  日期：2013.3.28

  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.