1,2-Bis-(4'-fluorphenyl)-pyrazolidin-3,5-dion | 16858-27-8

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯和取代衍生物
• 英文名称: 1,2-Bis-(4'-fluorphenyl)-pyrazolidin-3,5-dion
• 英文别名: 1,2-bis-(4-fluoro-phenyl)-pyrazolidine-3,5-dione；1,2-bis(4-fluorophenyl)pyrazolidine-3,5-dione
• CAS: 16858-27-8
• 化学式: C₁₅H₁₀F₂N₂O₂
• 分子量: 288.253
• InChiKey: IENHKOXCJLCCJO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  21
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.07
• 拓扑面积：
  40.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为产物：
  描述：

  bis(4-fluorophenyl)diazene 在 sodium ethanolate 、 氯化铵 、 锌 作用下， 以 乙醇 、 丙酮 为溶剂， 反应 9.5h， 生成 1,2-Bis-(4'-fluorphenyl)-pyrazolidin-3,5-dion
  参考文献：
  名称：

  Pyrazolidine-3,5-diones and 5-Hydroxy-1H-pyrazol-3(2H)-ones, Inhibitors of UDP-N-acetylenolpyruvyl Glucosamine Reductase

  摘要：

  A series of pyrazolidine-3,5-dione and 5-hydroxy-1H-pyrazol-3(2H)-one inhibitors of Escherichia coli UDP-N-acetylenolpyruvyl glucosamine reductase (MurB) has been prepared. The 5-hydroxy-1H-pyrazol-3(2H)ones show low micromolar IC50 values versus E. coli MurB and submicromolar minimal inhibitory concentrations ( MIC) against Staphylococcus aureus GC 1131, Enterococcus faecalis GC 2242, Streptococcus pneumoniae GC 1894, and E. coli GC 4560 imp, a strain with increased outer membrane permeability. None of these compounds show antimicrobial activity against Candida albicans, a marker of eukaryotic toxicity. Moreover, these compounds inhibit peptidoglycan biosynthesis, as assessed by measuring the amount of soluble peptidoglycan produced by Streptococcus epidermidis upon incubation with compounds. A partial least squares projection to latent structures analysis shows that improving MurB potency and MIC values correlate with increasing lipophilicity of the C-4 substituent of the 5-hydroxy-1H-pyrazol-3(2H)-one core. Docking studies using FLO and PharmDock produced several binding orientations for these molecules in the MurB active site.

  DOI：

  10.1021/jm060499t

文献信息

• Pyrazolidine-3,5-diones and 5-Hydroxy-1<i>H</i>-pyrazol-3(2<i>H</i>)-ones, Inhibitors of UDP-<i>N</i>-acetylenolpyruvyl Glucosamine Reductase
  作者：Adam M. Gilbert、Amedeo Failli、Jay Shumsky、Youjun Yang、Anatoly Severin、Guy Singh、William Hu、David Keeney、Peter J. Petersen、Alan H. Katz

  DOI：10.1021/jm060499t

  日期：2006.10.1

  A series of pyrazolidine-3,5-dione and 5-hydroxy-1H-pyrazol-3(2H)-one inhibitors of Escherichia coli UDP-N-acetylenolpyruvyl glucosamine reductase (MurB) has been prepared. The 5-hydroxy-1H-pyrazol-3(2H)ones show low micromolar IC50 values versus E. coli MurB and submicromolar minimal inhibitory concentrations ( MIC) against Staphylococcus aureus GC 1131, Enterococcus faecalis GC 2242, Streptococcus pneumoniae GC 1894, and E. coli GC 4560 imp, a strain with increased outer membrane permeability. None of these compounds show antimicrobial activity against Candida albicans, a marker of eukaryotic toxicity. Moreover, these compounds inhibit peptidoglycan biosynthesis, as assessed by measuring the amount of soluble peptidoglycan produced by Streptococcus epidermidis upon incubation with compounds. A partial least squares projection to latent structures analysis shows that improving MurB potency and MIC values correlate with increasing lipophilicity of the C-4 substituent of the 5-hydroxy-1H-pyrazol-3(2H)-one core. Docking studies using FLO and PharmDock produced several binding orientations for these molecules in the MurB active site.