ethyl 6,7-difluoro-1-(4-fluorophenyl)-4-oxo-1,4-dihydroquinoline-3-carboxylate | 108138-16-5

• 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 6,7-difluoro-1-(4-fluorophenyl)-4-oxo-1,4-dihydroquinoline-3-carboxylate
• 英文别名: 1-(p-fluorophenyl)-6,7-difluoro-1,4-dihydro-4-oxo-quinoline-3-carboxylic acid ethyl ester；ethyl 1-(4-fluorophenyl)-6,7-difluoro-1,4-dihydro-4-oxoquinoline-3-carboxylate；ethyl 1-(4-fluorophenyl)-6,7-difluoro-1,4-dihydro-4-oxoquinolin-3-carboxylate；6,7-Difluoro-1-(4-fluorophenyl)-1,4-dihydro-4-oxo-quinoline-3-carboxylic acid ethyl ester；ethyl 6,7-difluoro-1-(4-fluorophenyl)-4-oxoquinoline-3-carboxylate
• CAS: 108138-16-5
• 化学式: C₁₈H₁₂F₃NO₃
• 分子量: 347.293
• InChiKey: ADFROHOWXJREBY-UHFFFAOYSA-N

物化性质

• 沸点：
  470.7±45.0 °C(Predicted)
• 密度：
  1.411±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.11
• 拓扑面积：
  46.6
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl 6,7-difluoro-1-(4-fluorophenyl)-4-oxo-1,4-dihydroquinoline-3-carboxylate 在 盐酸 、 溶剂黄146 作用下， 以86%的产率得到6,7-二氟-1-(4-氟苯基)-4-氧代-1,4-二氢喹啉-3-羧酸
  参考文献：
  名称：

  Heterocycylic-substituted quinoline-carboxylic acids

  摘要：

  1-取代-6-氟-7-杂环-1,4-二氢喹诺-1-(或二氢萘啉)-4-酮羧酸具有抗菌性能。7-杂环基团是一个双环基团，其中一个环是饱和的，另一个环是不饱和的。

  公开号：

  US05037834A1
• 作为产物：
  描述：

  2,4,5-三氟苯甲酰乙酸乙酯 在 乙酸酐 、 sodium hydride 作用下， 以 四氢呋喃 、 二氯甲烷 、 mineral oil 为溶剂， 生成 ethyl 6,7-difluoro-1-(4-fluorophenyl)-4-oxo-1,4-dihydroquinoline-3-carboxylate
  参考文献：
  名称：

  Synthesis of [1-15N,2-13C]-labeled difloxacin

  摘要：

  The synthesis of [1-N-15,2-C-13]-difloxacin, an arylfluoroquinolone antibacterial agent, is reported. As a crucial initial step, the starting materials ethyl 2,4,5-trifluorobenzoylacetate, [formyl-C-13]-triethyl orthoformate, and [N-15]-4-fluoroaniline were reacted to ethyl [N-15,3-C-13]-3-(4-fluoroanilino)-2-(2,4,5-trifluorobenzoyl) acrylate. After cyclization and ester cleavage, the resulting intermediate was reacted with 1-methylpiperazine to [1-N-15,2-C-13]-1-(4-fluorophenyl)-6-fluoro-7-(4-methyl-1-piperazinyl)-1,4-dihydro-4-oxoquinoline-3-carboxylate, i.e., [1-N-15,2-C-13]-difloxacin. The overall yield was 62% based on the non-labeled and 43% based on the labeled starting materials (both used in 1.4 molar excess). The product was identified by H-1-, C-13-, and N-15-NMR spectroscopy and by cochromatography (TLC, HPLC) with an authentic reference; its purity (HPLC) was above 98%. Prior to synthesis of [1-N-15,2-C-13]-difloxacin, non-labeled difloxacin was synthesized in order to optimize procedures and to identify and characterize all intermediates.

  DOI：

  10.1007/s00706-009-0158-y

文献信息

• Design, synthesis, and properties of (4S)-7-(4-amino-2-substituted-pyrrolidin-1-yl)quinolone-3-carboxylic acids
  作者：Terry Rosen、Daniel T. W. Chu、Isabella M. Lico、Prabhavathi B. Fernandes、Kennan Marsh、Linus Shen、Valerie G. Cepa、Andre G. Pernet

  DOI：10.1021/jm00403a020

  日期：1988.8

  The quinolonecarboxylic acids constitute a class of extremely potent and orally active broad-spectrum antibacterial agents. These compounds have been shown to inhibit DNA gyrase, a key enzyme in bacterial DNA replication. The 7-(3-aminopyrrolidinyl)quinolone A-60969 (1) is a particularly potent member of this class and is currently undergoing clinical evaluation. We have studied a series of enantiomerically

  喹诺酮羧酸构成一类非常有效且具有口服活性的广谱抗菌剂。这些化合物已显示出抑制DNA回旋酶的作用，而DNA回旋酶是细菌DNA复制中的关键酶。7-（3-氨基吡咯烷基）喹诺酮A-60969（1）是此类中特别有效的成员，目前正在临床评估中。我们已经研究了一系列对映体均质的（4S）-7-（4-氨基-2-取代的吡咯烷基）喹诺酮类药物，以利用吡咯烷部分的2位改善此类药物的溶解度和药代动力学性质化合物，同时仍保持有效的抗菌活性。我们已经发现，在吡咯烷环的2-位上的绝对立体化学对于维持这种活性至关重要。在本文中，我们报告了该系列化合物的不对称合成以及体外和体内结构-活性关系的完整详细信息，以及与结构修饰相关的理化特性，例如水溶性和logP。我们还讨论了这些化合物中的几种在小鼠中的药代动力学特性，以及在本研究中在狗中具有最佳药物总体特性的59的药代动力学。
• 一种高效环保制备喹诺酮类化合物的方法
  申请人：云南民族大学

  公开号：CN108892639B

  公开（公告）日：2021-05-14

  本发明公开了一种高效环保制备喹诺酮类化合物的方法。氟苯甲酰乙酸乙酯、原甲酸三乙酯、胺类化合物为原料，在无溶剂和无催化剂的条件下维持温度130℃反应24h合成喹诺酮类化合物。同时在反应完成后，通过减压抽滤使用乙酸乙酯、石油醚和甲醇洗涤，产品纯度能到98.9%以上。本发明所述的喹诺酮的合成工艺简单、操作方便、收率较高、绿色环保。本发明所述的高效环保合成喹诺酮类化合物的制备方法是以简单易得的二羰基化合物、原甲酸三乙酯和胺类化合物三组分化合物一起投料降低原料成本，且反应过程无任何溶剂和催化剂的使用，从根本上解决了原路线污染较大、操作难度高等问题。
• Fluorinated benzoyl compounds
  申请人：Asahi Glass Company Ltd.

  公开号：US05093515A1

  公开（公告）日：1992-03-03

  A 2-chloro-4,5-difluorobenzoyl compound of the formula: ##STR1## wherein R.sup.2 is a lower alkyl group, and R.sup.7 is a 2,4-difluorophenyl group or a 4-fluorophenyl group.

  公式为：##STR1## 其中R.sup.2是较低的烷基基团，R.sup.7是2,4-二氟苯基基团或4-氟苯基基团的2-氯-4,5-二氟苯甲酰化合物。
• Thiazolyl and oxazolyl[5,4-c]piperidyl-substituted quinolone-carboxylic
  申请人：Pfizer Inc.

  公开号：US05214051A1

  公开（公告）日：1993-05-25

  Thiazolyl and oxazolyl [5,4-c] piperidyl-substituted quinolone-carboxylic acids and related analogs thereof having antibacterial properties are disclosed.

  本发明揭示了具有抗菌性的噻唑基和氧唑基[5,4-c]哌啶取代的喹诺酸羧酸及其相关类似物。
• Effect of Lipophilicity at N-1 on Activity of Fluoroquinolones against Mycobacteria
  作者：Thomas E. Renau、Joseph P. Sanchez、Martin A. Shapiro、Julie A. Dever、Stephen J. Gracheck、John M. Domagala

  DOI：10.1021/jm00015a021

  日期：1995.7

  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.