ethyl 2-heptyl-4-oxo-1,4-dihydroquinoline-3-carboxylate | 1609401-96-8

• 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: ethyl 2-heptyl-4-oxo-1,4-dihydroquinoline-3-carboxylate
• 英文别名: ethyl 2-heptyl-4-oxo-1H-quinoline-3-carboxylate
• CAS: 1609401-96-8
• 化学式: C₁₉H₂₅NO₃
• 分子量: 315.412
• InChiKey: CFWAVRMLMILPFK-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.3
• 重原子数：
  23
• 可旋转键数：
  9
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  55.4
• 氢给体数：
  1
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  ethyl 2-heptyl-4-oxo-1,4-dihydroquinoline-3-carboxylate 在 ammonium hydroxide 、 水 、 sodium hydroxide 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 9.0h， 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：

  靛红酸酐 、 3-羰基癸酸乙酯 在 sodium hydride 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 以57%的产率得到ethyl 2-heptyl-4-oxo-1,4-dihydroquinoline-3-carboxylate
  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

• PQSR modulators
  申请人：HELMHOLTZ-ZENTRUM FÜR INFEKTIONSFORSCHUNG GMBH

  公开号：US10472326B2

  公开（公告）日：2019-11-12

  The present invention relates to compounds according to general formula (I); to pharmaceutical compositions comprising one or more of the compound(s); and to the use of the compound(s) as anti-infectives.

  本发明涉及符合通式（I）的化合物；含有一种或多种该化合物的药物组合物；以及该化合物作为抗感染药的用途。
• PQSR MODULATORS
  申请人：HELMHOLTZ-ZENTRUM FÜR INFEKTIONSFORSCHUNG GMBH

  公开号：US20170022165A1

  公开（公告）日：2017-01-26

  The present invention relates to compounds according to general formula (I); to pharmaceutical compositions comprising one or more of the compound(s); and to the use of the compound(s) as anti-infectives.
• 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.