2-heptyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid | 1357004-25-1

• 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-heptyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
• 英文别名: 2-heptyl-4-oxo-1H-quinoline-3-carboxylic acid
• CAS: 1357004-25-1
• 化学式: C₁₇H₂₁NO₃
• 分子量: 287.359
• InChiKey: LJKUYDZOWKIUHC-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  21
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.41
• 拓扑面积：
  66.4
• 氢给体数：
  2
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-heptyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 在 ammonium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 5.0h， 生成 2-heptyl-4-oxo-1,4-dihydroquinoline-3-carboxamide
  参考文献：
  名称：

  Optimization of anti-virulence PqsR antagonists regarding aqueous solubility and biological properties resulting in new insights in structure–activity relationships

  摘要：

  Increasing antibiotic resistance urgently requires novel therapeutic options to combat bacterial infections. The anti-virulence therapy selectively intervening with pathogenicity without affecting bacterial viability is such a strategy to overcome resistance. We consider the virulence regulator PqsR as an attractive target in the human pathogen Pseudomonas aeruginosa, and recently discovered the first PqsR antagonists, which, however, suffered from poor aqueous solubility. In this work, the antagonists were structurally modified to become more soluble, and their structure-activity as well as structure-property relationships were studied. A novel promising compound with improved solubility and enhanced antivirulence activity was discovered (IC50: 3.8 mu M, pyocyanin). Our findings emphasize the crucial role of substituents at the 3-position and the carbonyl group at the 4-position for ligand receptor interactions, and illuminate the way for further optimization of PqsR antagonists as anti-virulence agents. (c) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.04.016
• 作为产物：
  描述：

  3-羰基癸酸乙酯 在 水 、 sodium hydride 、 sodium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 2-heptyl-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
  参考文献：
  名称：

  Optimization of anti-virulence PqsR antagonists regarding aqueous solubility and biological properties resulting in new insights in structure–activity relationships

  摘要：

  Increasing antibiotic resistance urgently requires novel therapeutic options to combat bacterial infections. The anti-virulence therapy selectively intervening with pathogenicity without affecting bacterial viability is such a strategy to overcome resistance. We consider the virulence regulator PqsR as an attractive target in the human pathogen Pseudomonas aeruginosa, and recently discovered the first PqsR antagonists, which, however, suffered from poor aqueous solubility. In this work, the antagonists were structurally modified to become more soluble, and their structure-activity as well as structure-property relationships were studied. A novel promising compound with improved solubility and enhanced antivirulence activity was discovered (IC50: 3.8 mu M, pyocyanin). Our findings emphasize the crucial role of substituents at the 3-position and the carbonyl group at the 4-position for ligand receptor interactions, and illuminate the way for further optimization of PqsR antagonists as anti-virulence agents. (c) 2014 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2014.04.016

文献信息

• METHODS AND USES RELATING TO THE IDENTIFICATION OF COMPOUND ASSOCIATED WITH BACTERIAL INFECTION
  申请人：Müller Rolf

  公开号：US20130123360A1

  公开（公告）日：2013-05-16

  The present invention relates to a method of identifying a compound useful for the treating, reducing or preventing pathogenic infection caused by a microorganism and to the use of the PqsD protein or a functional fragment or variant thereof for the identification of a compound having said effect.
• Optimization of anti-virulence PqsR antagonists regarding aqueous solubility and biological properties resulting in new insights in structure–activity relationships
  作者：Cenbin Lu、Benjamin Kirsch、Christine K. Maurer、Johannes C. de Jong、Andrea Braunshausen、Anke Steinbach、Rolf W. Hartmann

  DOI：10.1016/j.ejmech.2014.04.016

  日期：2014.5

  Increasing antibiotic resistance urgently requires novel therapeutic options to combat bacterial infections. The anti-virulence therapy selectively intervening with pathogenicity without affecting bacterial viability is such a strategy to overcome resistance. We consider the virulence regulator PqsR as an attractive target in the human pathogen Pseudomonas aeruginosa, and recently discovered the first PqsR antagonists, which, however, suffered from poor aqueous solubility. In this work, the antagonists were structurally modified to become more soluble, and their structure-activity as well as structure-property relationships were studied. A novel promising compound with improved solubility and enhanced antivirulence activity was discovered (IC50: 3.8 mu M, pyocyanin). Our findings emphasize the crucial role of substituents at the 3-position and the carbonyl group at the 4-position for ligand receptor interactions, and illuminate the way for further optimization of PqsR antagonists as anti-virulence agents. (c) 2014 Elsevier Masson SAS. All rights reserved.