2-[4-(propyloxy)phenyl]quinolin-4-ol | 1260244-03-8

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 喹啉及其衍生物
• 英文名称: 2-[4-(propyloxy)phenyl]quinolin-4-ol
• 英文别名: 2-(4-propoxyphenyl)-4-hydroxyquinoline；2-(4-propoxyphenyl)quinolin-4-ol；2-(4-propoxyphenyl)-1H-quinolin-4-one
• CAS: 1260244-03-8
• 化学式: C₁₈H₁₇NO₂
• 分子量: 279.338
• InChiKey: WXEXTSSBSXMNNU-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  21
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.17
• 拓扑面积：
  38.3
• 氢给体数：
  1
• 氢受体数：
  3

反应信息

• 作为反应物：
  描述：

  2-[4-(propyloxy)phenyl]quinolin-4-ol 在 potassium carbonate 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 生成 4-[2-(1-azepanyl)ethoxy]-2-(4-propoxyphenyl)quinoline
  参考文献：
  名称：

  Re-evolution of the 2-Phenylquinolines: Ligand-Based Design, Synthesis, and Biological Evaluation of a Potent New Class of Staphylococcus aureus NorA Efflux Pump Inhibitors to Combat Antimicrobial Resistance

  摘要：

  Overexpression of efflux pumps is an important mechanism by which bacteria evade the effects of antimicrobial agents that are substrates. NorA is a Staphylococcus aureus efflux pump that confers reduced susceptibility to many structurally unrelated agents, including fluoroquinolones, biocides, and dyes, resulting in a multidrug resistant (MDR) phenotype. In this work, a series of 2-phenylquinoline derivatives was designed by means of ligand-based pharmacophore modeling in an attempt to identify improved S. aureus NorA efflux pump inhibitors (EPIs). Most of the 2-phenylquinoline derivatives displayed potent EPI activity against the norA overexpressing strain SA-1199B. The antibacterial activity of ciprofloxacin, when used in combination with some of the synthesized compounds, was completely restored in SA-1199B and SA-K2378, a strain overexpressing norA from a multicopy plasmid. Compounds 3m and 3q also showed potent synergistic activity with the ethidium bromide dye in a strain overexpressing the MepA MDR efflux pump.

  DOI：

  10.1021/jm400262a
• 作为产物：
  描述：

  4-丙氧基苯甲酸 在 potassium tert-butylate 、 三乙胺 、 叔丁醇 作用下， 以 四氢呋喃 为溶剂， 反应 6.0h， 生成 2-[4-(propyloxy)phenyl]quinolin-4-ol
  参考文献：
  名称：

  Evolution from a Natural Flavones Nucleus to Obtain 2-(4-Propoxyphenyl)quinoline Derivatives As Potent Inhibitors of the S. aureus NorA Efflux Pump

  摘要：

  Overexpression of efflux pumps is an important mechanism by which bacteria evade the effects of substrate antimicrobial agents. Inhibition of such pumps is a promising strategy to circumvent this resistance mechanism. NorA is a Staphylococcus aureus efflux pump that confers reduced susceptibility to many structurally unrelated agents, including fluoroquinolones, resulting in a multidrug resistant phenotype. In this work, a series of 2-phenyl-4(1H)-quinolone and 2-phenyl-4-hydroxyquinoline derivatives, obtained by modifying the flavone nucleus of known efflux pump inhibitors (EPIs), were synthesized in an effort to identify more potent S. aureus NorA EPIs. The 2-phenyl-4-hydroxyquinoline derivatives 28f and 29f display potent EPI activity against SA-1199B, a strain that overexpresses norA, in an ethidium bromide efflux inhibition assay. The same compounds, in combination with ciprofloxacin, were able to completely restore its antibacterial activity against both S. aureus SA-K2378 and SA-1199B, narA-overexpressing strains.

  DOI：

  10.1021/jm200370y

文献信息

• Evolution from a Natural Flavones Nucleus to Obtain 2-(4-Propoxyphenyl)quinoline Derivatives As Potent Inhibitors of the <i>S. aureus</i> NorA Efflux Pump
  作者：Stefano Sabatini、Francesca Gosetto、Giuseppe Manfroni、Oriana Tabarrini、Glenn W. Kaatz、Diixa Patel、Violetta Cecchetti

  DOI：10.1021/jm200370y

  日期：2011.8.25

  Overexpression of efflux pumps is an important mechanism by which bacteria evade the effects of substrate antimicrobial agents. Inhibition of such pumps is a promising strategy to circumvent this resistance mechanism. NorA is a Staphylococcus aureus efflux pump that confers reduced susceptibility to many structurally unrelated agents, including fluoroquinolones, resulting in a multidrug resistant phenotype. In this work, a series of 2-phenyl-4(1H)-quinolone and 2-phenyl-4-hydroxyquinoline derivatives, obtained by modifying the flavone nucleus of known efflux pump inhibitors (EPIs), were synthesized in an effort to identify more potent S. aureus NorA EPIs. The 2-phenyl-4-hydroxyquinoline derivatives 28f and 29f display potent EPI activity against SA-1199B, a strain that overexpresses norA, in an ethidium bromide efflux inhibition assay. The same compounds, in combination with ciprofloxacin, were able to completely restore its antibacterial activity against both S. aureus SA-K2378 and SA-1199B, narA-overexpressing strains.
• Re-evolution of the 2-Phenylquinolines: Ligand-Based Design, Synthesis, and Biological Evaluation of a Potent New Class of Staphylococcus aureus NorA Efflux Pump Inhibitors to Combat Antimicrobial Resistance
  作者：Stefano Sabatini、Francesca Gosetto、Nunzio Iraci、Maria Letizia Barreca、Serena Massari、Luca Sancineto、Giuseppe Manfroni、Oriana Tabarrini、Mirjana Dimovska、Glenn W. Kaatz、Violetta Cecchetti

  DOI：10.1021/jm400262a

  日期：2013.6.27

  Overexpression of efflux pumps is an important mechanism by which bacteria evade the effects of antimicrobial agents that are substrates. NorA is a Staphylococcus aureus efflux pump that confers reduced susceptibility to many structurally unrelated agents, including fluoroquinolones, biocides, and dyes, resulting in a multidrug resistant (MDR) phenotype. In this work, a series of 2-phenylquinoline derivatives was designed by means of ligand-based pharmacophore modeling in an attempt to identify improved S. aureus NorA efflux pump inhibitors (EPIs). Most of the 2-phenylquinoline derivatives displayed potent EPI activity against the norA overexpressing strain SA-1199B. The antibacterial activity of ciprofloxacin, when used in combination with some of the synthesized compounds, was completely restored in SA-1199B and SA-K2378, a strain overexpressing norA from a multicopy plasmid. Compounds 3m and 3q also showed potent synergistic activity with the ethidium bromide dye in a strain overexpressing the MepA MDR efflux pump.