2-heptyl-3-(hydroxymethyl)-6-nitroquinolin-4(1H)-one | 1593849-58-1

• 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-3-(hydroxymethyl)-6-nitroquinolin-4(1H)-one
• 英文别名: 2-heptyl-3-(hydroxymethyl)-6-nitro-1H-quinolin-4-one
• CAS: 1593849-58-1
• 化学式: C₁₇H₂₂N₂O₄
• 分子量: 318.373
• InChiKey: IJCSNVRTCJOFHH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  4.4
• 重原子数：
  23
• 可旋转键数：
  7
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.47
• 拓扑面积：
  95.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  2-heptyl-3-(hydroxymethyl)-6-nitroquinolin-4(1H)-one 在 manganese(IV) oxide 作用下， 以 四氢呋喃 为溶剂， 以80 mg的产率得到2-heptyl-6-nitro-4-oxo-1,4-dihydroquinoline-3-carbaldehyde
  参考文献：
  名称：

  克服铜绿假单胞菌中PqsR拮抗剂的意外功能反转：靶向pqs群体感应的体内有效抗毒剂

  摘要：

  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。

  DOI：

  10.1002/anie.201307547
• 作为产物：
  描述：

  5-硝基靛红酸酐 在 lithium aluminium tetrahydride 、 sodium hydride 作用下， 以 四氢呋喃 、 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 生成 2-heptyl-3-(hydroxymethyl)-6-nitroquinolin-4(1H)-one
  参考文献：
  名称：

  克服铜绿假单胞菌中PqsR拮抗剂的意外功能反转：靶向pqs群体感应的体内有效抗毒剂

  摘要：

  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。

  DOI：

  10.1002/anie.201307547

文献信息

• [EN] PQSR MODULATORS<br/>[FR] MODULATEURS DU PQSR
  申请人：HELMHOLTZ ZENTRUM FÜR INFEKTIONSFORSCHUNG GMBH

  公开号：WO2015149821A1

  公开（公告）日：2015-10-08

  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。
• 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。
• Design, synthesis, and evaluation of compounds capable of reducing Pseudomonas aeruginosa virulence
  作者：Mohammad Anwar Hossain、Narsimha Sattenapally、Hardik I. Parikh、Wei Li、Kendra P. Rumbaugh、Nadezhda A. German

  DOI：10.1016/j.ejmech.2019.111800

  日期：2020.1

  Anti-virulence approaches in the treatment of Pseudomonas aeruginosa (PA)-induced infections have shown clinical potential in multiple in vitro and in vivo studies. However, development of these compounds is limited by several factors, including the lack of molecules capable of penetrating the membrane of gram-negative organisms. Here, we report the identification of novel structurally diverse compounds that inhibit PqsR and LasR-based signaling and diminish virulence factor production and biofilm growth in two clinically relevant strains of P. aeruginosa. It is the first report where potential antivirulent agents were evaluated for inhibition of several virulence factors of PA. Finally, co-treatment with these inhibitors significantly reduced the production of virulence factors induced by the presence of subinhibitory levels of ciprofioxacin. Further, we have analyzed the drug-likeness profile of designed compounds using quantitative estimates of drug-likeness (QED) and confirmed their potential as hit molecules for further development. Published by Elsevier Masson SAS.
• 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