1-o-fluorophenyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-quinoline-3-carboxylic acid | 164662-38-8

• 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: 1-o-fluorophenyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-quinoline-3-carboxylic acid
• 英文别名: 3-Quinolinecarboxylic acid, 6-fluoro-1-(2-fluorophenyl)-1,4-dihydro-4-oxo-7-(1-piperazinyl)-；6-fluoro-1-(2-fluorophenyl)-4-oxo-7-piperazin-1-ylquinoline-3-carboxylic acid
• CAS: 164662-38-8
• 化学式: C₂₀H₁₇F₂N₃O₃
• 分子量: 385.37
• InChiKey: ARZDSVFJNIANND-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.3
• 重原子数：
  28
• 可旋转键数：
  3
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.2
• 拓扑面积：
  72.9
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为产物：
  描述：

  2,4,5-三氟苯甲酰乙酸乙酯 在 盐酸 、 乙酸酐 、 sodium hydride 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 生成 1-o-fluorophenyl-6-fluoro-1,4-dihydro-4-oxo-7-(1-piperazinyl)-quinoline-3-carboxylic acid
  参考文献：
  名称：

  Effect of Lipophilicity at N-1 on Activity of Fluoroquinolones against Mycobacteria

  摘要：

  The dramatic increase in drug resistant Mycobacterium tuberculosis has caused a resurgence in research targeted toward these organisms. As part of a systematic study to optimize the quinolone antibacterials against mycobacteria, we have prepared a series of N-1-phenylsubstituted derivatives to explore the effect of increasing lipophilicity on potency at this position. The compounds, synthesized by the modification of a literature procedure, were evaluated for activity against Gram-negative and Gram-positive bacteria, Mycobacterium fortuitum and Mycobacterium smegmatis, and the results correlated with log P, pK(a), and other attributes. The activity of the compounds against the rapidly growing, less hazardous organism M. fortuitum was used as a measure of M, tuberculosis activity. The results demonstrate that increasing lipophilic character by itself does not correlate with increased potency against mycobacteria. Rather, intrinsic activity against Gram-negative and/or Gram-positive bacteria is the governing factor for corresponding activity against mycobacteria.

  DOI：

  10.1021/jm00015a021

文献信息

• Syntheses and Biological Activities of NewN1-Aryl Substituted Quinolone Antibacterials
  作者：Jens Jürgens、Holger Schedletzky、Peter Heisig、Joachim K. Seydel、Bernd Wiedemann、Ulrike Holzgrabe

  DOI：10.1002/ardp.19963290403

  日期：——

  A series of quinolones with a systematically varied substitution at the phenyl ring at N1 has been synthesized. Three lipophilicity descriptors (log K, log P, Rm) and the pKa values have been determined as well as the microbiological activity: The MIC values for eight different strains of three Gram‐positive and three Gram‐negative species and the inhibitory concentrations of DNA supercoiling (IC90

  已经合成了一系列在 N1 苯环上具有系统变化取代的喹诺酮类药物。已经确定了三个亲脂性描述符（log K、log P、Rm）和 pKa 值以及微生物活性：三种革兰氏阳性菌和三种革兰氏阴性菌的八种不同菌株的 MIC 值以及测定 DNA 超螺旋（IC90 和 IC100）的抑制浓度。从主成分和 QSAR 分析可以推导出与全细胞系统相关的抗菌活性与电子特性以及苯环上的取代基长度之间的关系。无细胞系统中的活性受替代品的亲脂性和宽度控制。据推测，喹诺酮类药物在以极性氨基酸为特征的 DNA 促旋酶-DNA 复合物中占据特定位置。这与突变回旋酶研究的结果一致。
• Quinoline antibacterial compounds
  申请人：ABBOTT LABORATORIES

  公开号：EP0131839B1

  公开（公告）日：1989-02-01
• US4730000A
  申请人：——

  公开号：US4730000A

  公开（公告）日：1988-03-08
• US4994599A
  申请人：——

  公开号：US4994599A

  公开（公告）日：1991-02-19
• US5262559A
  申请人：——

  公开号：US5262559A

  公开（公告）日：1993-11-16