2-heptyl-6-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid | 1593849-61-6

• 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-6-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
• 英文别名: 2-heptyl-6-nitro-4-oxo-1H-quinoline-3-carboxylic acid
• CAS: 1593849-61-6
• 化学式: C₁₇H₂₀N₂O₅
• 分子量: 332.356
• InChiKey: GBXTUMVGCMBUFH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5
• 重原子数：
  24
• 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：
  112
• 氢给体数：
  2
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  2-heptyl-6-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 在 N,N'-羰基二咪唑 、 N-甲基吗啉 、 盐酸羟胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 以15%的产率得到2-heptyl-N-hydroxy-6-nitro-4-oxo-1,4-dihydroquinoline-3-carboxamide
  参考文献：
  名称：

  [EN] PQSR MODULATORS
  [FR] MODULATEURS DU PQSR

  摘要：

  本发明涉及一般式（I）的化合物；含有一种或多种化合物的制药组合物；以及将该化合物用作抗感染剂的用途。

  公开号：

  WO2015149821A1
• 作为产物：
  描述：

  3-氧代癸酸甲酯 在 sodium hydride 、 sodium hydroxide 作用下， 以 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 4.0h， 生成 2-heptyl-6-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
  参考文献：
  名称：

  The requirements at the C-3 position of alkylquinolones for signalling in Pseudomonas aeruginosa

  摘要：

  细菌对抗生素的耐药性越来越强，而新抗生素的发现却越来越少，这种 "完美风暴 "使得我们必须寻找新的创新策略来治疗细菌感染。

  DOI：

  10.1039/c6ob01930g

文献信息

• Structure–functionality relationship and pharmacological profiles of Pseudomonas aeruginosa alkylquinolone quorum sensing modulators
  作者：Ahmed A. M. Kamal、Lucia Petrera、Jens Eberhard、Rolf W. Hartmann

  DOI：10.1039/c7ob00263g

  日期：——

  Alkylquinolone derived compounds revealed four pharmacological profiles for PqsR modulation. Molecular docking illuminated the structural requirements. Only inverse agonists were effective pathoblockers inhibiting pyocyanin.

  烷基喹啉衍生物揭示了PqsR调节的四种药理特性。分子对接揭示了结构要求。只有逆向激动剂才是有效的病原体阻断剂，能抑制吡啶蓝素的产生。
• Overcoming the Unexpected Functional Inversion of a PqsR Antagonist in<i>Pseudomonas aeruginosa</i>: An In Vivo Potent Antivirulence Agent Targeting<i>pqs</i>Quorum Sensing
  作者：Cenbin Lu、Christine K. Maurer、Benjamin Kirsch、Anke Steinbach、Rolf W. Hartmann

  DOI：10.1002/anie.201307547

  日期：2014.1.20

  The virulence regulator PqsR of Pseudomonas aeruginosa is considered as an attractive target for attenuating the bacterial pathogenicity without eliciting resistance. However, despite efforts and desires, no promising PqsR antagonist has been discovered thus far. Now, a surprising functionality change of a highly affine PqsR antagonist in P. aeruginosa is revealed, which is mediated by a bacterial

  铜绿假单胞菌的毒力调节剂PqsR被认为是在不引起耐药性的情况下减弱细菌致病性的诱人靶标。然而，尽管作出了努力和期望，迄今为止尚未发现有希望的PqsR拮抗剂。现在，揭示了铜绿假单胞菌中一种高度亲和力的PqsR拮抗剂的功能发生了令人惊讶的变化，这是由细菌信号分子合酶介导的，并导致细胞效力低下。易感位置的封锁导致发现了第一种在体内有效并靶向PqsR的抗毒化合物，因此为这种新型抗毒疗法提供了概念验证。
• 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。
• 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.
• PQSR MODULATORS
  申请人：Helmholtz-Zentrum für Infektionsforschung GmbH

  公开号：EP3126333B1

  公开（公告）日：2018-08-01