1-(2,4-二氟苯基)-6,7-二氟-1,4-二氢-4-氧代喹啉-3-羧酸 | 103995-01-3

• 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
• 中文名称: 1-(2,4-二氟苯基)-6,7-二氟-1,4-二氢-4-氧代喹啉-3-羧酸
• 中文别名: 1-(2,4-二氟苯基)-6,7-二氟-4-氧代-1,4-二氢喹啉-3-甲酸
• 英文名称: 6,7-difluoro-1-(2,4-difluorophenyl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
• 英文别名: 6,7-difluoro-1-(2,4-difluorophenyl)-1,4-dihydro-4-oxo-3-quinoline-carboxylic acid；1-(2,4-difluorophenyl)-6,7-difluoro-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid；1-(2,4-difluorophenyl)-6,7-difluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid；1-(2,4-difluorophenyl)-6,7-difluoro-4-oxoquinoline-3-carboxylic acid
• CAS: 103995-01-3
• 化学式: C₁₆H₇F₄NO₃
• 分子量: 337.23
• InChiKey: BNYMEXVJUDGTJS-UHFFFAOYSA-N

物化性质

• 熔点：
  239-241 °C(Solv: chloroform (67-66-3); ethanol (64-17-5))
• 沸点：
  472.2±45.0 °C(Predicted)
• 密度：
  1.618±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  24
• 可旋转键数：
  2
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.0
• 拓扑面积：
  57.6
• 氢给体数：
  1
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1-(2,4-二氟苯基)-6,7-二氟-1,4-二氢-4-氧代喹啉-3-羧酸 在 palladium on activated charcoal N-甲基吗啉 、 吡啶 、 氢气 、 三乙胺 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 35.0h， 生成 7-[(2S,3R)-3-[[(2S)-2-aminopropanoyl]amino]-2-methylazetidin-1-yl]-1-(2,4-difluorophenyl)-6-fluoro-4-oxoquinoline-3-carboxylic acid
  参考文献：
  名称：

  7-氮杂环丁烷基喹诺酮类作为抗菌剂。3.含有7-（3-氨基-2-甲基-1-氮杂环丁烷基）部分的立体异构体的合成，性质和结构-活性关系。

  摘要：

  一系列立体化学纯的7-（3-氨基-2-甲基-1-氮杂环丁烷基）-1,4-二氢-6-氟-4-氧代喹啉-和-1,8-萘啶-3-羧酸制备了位于1、5和8位的取代基，以确定手性相对于外消旋混合物的效价和体内功效的影响（第2部分，参见：J. Med.Chem。1994，37， 4195-4210）。一系列手性9-氟-2,3-二氢-3-甲基-7-氧-10-（取代的1-氮杂环丁烷基）-7H-吡啶[1,2,3-de] -1,4-苯并恶嗪合成-6-羧酸以研究氮杂环丁烷部分对三环喹诺酮抗菌剂的作用。制备了一系列手性萘啶24a和24b以及喹诺酮33a（cetefloxacin）的氨基酸前药，并评估了其抗菌活性，溶解度和药代动力学行为。通过对拆分的氮杂环丁醇（15）和化合物25a（E-4767）的一种非对映异构盐进行X射线分析，可以确定新的氮杂环丁烷基喹诺酮类化合物的绝对构型，该化合物在体外和体内的总体情况最佳。

  DOI：

  10.1021/jm00007a017
• 作为产物：
  描述：

  2,4,5-三氟苯甲酰氯 在 盐酸 、 正丁基锂 、 biquinoline 、 乙酸酐 、 sodium hydride 作用下， 以 四氢呋喃 、 三氟乙酸 为溶剂， 反应 64.25h， 生成 1-(2,4-二氟苯基)-6,7-二氟-1,4-二氢-4-氧代喹啉-3-羧酸
  参考文献：
  名称：

  Synthesis, antibacterial activities, and pharmacological properties of enantiomers of temafloxacin hydrochloride

  摘要：

  Temafloxacin hydrochloride [(+/-)-7-(3-methylpiperazin-1-yl)-6-fluro-1-(2,4-difluorophenyl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid hydrochloride] is a potent member of the 4-pyridone-3-carboxylic acid class of antibacterial agents and is currently under clinical development as a broad-spectrum antimicrobial agent. It is a racemate having a chiral center at the C3 of the 7-piperazin-1-yl group. The two enantiomers were synthesized and tested for their antibacterial activities. Although no difference in in vitro antibacterial activities was observed, a minor difference in in vivo antibacterial activities was observed. However, they both exhibited similar pharmacological profiles.

  DOI：

  10.1021/jm00105a025

文献信息

• Structure−Activity Relationships of the Quinolone Antibacterials against Mycobacteria:  Effect of Structural Changes at N-1 and C-7
  作者：Thomas E. Renau、Joseph P. Sanchez、Jeffrey W. Gage、Julie A. Dever、Martin A. Shapiro、Stephen J. Gracheck、John M. Domagala

  DOI：10.1021/jm9507082

  日期：1996.1.1

  smegmatis as well as Gram-negative and Gram-positive bacteria. The activity of the compounds against M. fortuitum was used as a barometer of M. tuberculosis activity. The results demonstrate that (i) the activity against mycobacteria was related more to antibacterial activity than to changes in the lipophilicity of the compounds, (ii) the antimycobacterial activity imparted by the N-1 substituent was in the

  对常规药物治疗有抵抗力的结核感染的再次出现表明需要针对结核分枝杆菌的替代化学疗法。作为优化针对结核分枝杆菌的喹诺酮类抗菌药物研究的一部分，我们准备了一系列N-1-和C-7取代的喹诺酮类化合物，以研究这两个位置上喹诺酮类修饰物与活性之间的特定结构-活性关系。对抗分枝杆菌。通过文献方法合成的化合物被评估了对福分枝杆菌和耻垢分枝杆菌以及革兰氏阴性和革兰氏阳性细菌的活性。化合物对堡垒分枝杆菌的活性用作结核分枝杆菌活性的晴雨表。
• 7-isoindolinyl-quinolone-carboxylic acid derivatives
  申请人：Bayer Aktiengesellschaft

  公开号：US05464796A1

  公开（公告）日：1995-11-07

  The invention relates to new quinolone- and naphthyridonecarboxylic acid derivatives which are substituted in the 7-position by a partly hydrogenated isoindolinyl ring, processes for their preparation and antibacterial agents and feed additives containing these compounds.

  本发明涉及新的7-位部分氢化的异喹啉基取代的喹诺酮和萘啶酮羧酸衍生物，它们的制备方法，以及含有这些化合物的抗菌剂和饲料添加剂。
• [EN] PROCESSES FOR PREPARING QUINOLONECARBOXYLATE DERIVATIVES<br/>[FR] PROCEDE DE PREPARATION DE DERIVES DE QUINOLONECARBOXYLATE
  申请人：YUHAN CORP

  公开号：WO2004056781A1

  公开（公告）日：2004-07-08

  The present invention provides a process for preparing quinolonecarboxylate derivatives under a mild condition in high yield, so as to be favorably applied to a large-scale mass production thereof.

  本发明提供了一种在温和条件下以高收率制备喹诺酮羧酸酯衍生物的方法，从而有利于其大规模量产的应用。
• Quinoline, naphthyridine and pyridobenzoxazine derivatives
  申请人：Abbott Laboratories

  公开号：US05137892A1

  公开（公告）日：1992-08-11

  Novel antibacterial compounds are disclosed having the formula ##STR1## as well as pharmaceutically acceptable salts, esters, amide and prodrugs thereof, wherein R.sup.1 is selected from the group consisting of (a) lower alkyl, (b) halo(lower alkyl), (c) lower alkyl(alkynyl), (d) lower cycloalkyl, (e) lower alkylamino, (f) nitrogen-containing aromatic heterocycle, (g) bicyclic alkyl and (h) phenyl; R.sup.2 is selected from the group consisting of hydrogen, lower alkyl, a pharmaceutically acceptable cation, and a prodrug ester group; R.sup.3 and R.sup.4 are independently selected from the group consisting of hydrogen, halogen, amino, and lower alkyl; R.sup.5 is either a nitrogen-containing heterocycle or a nitrogen-containing spiro-bicyclic-heterocycle; and A is N or C--R.sup.6, wherein R.sup.6 is selected from the group consisting of hydrogen, halogen, lower alkyl, and lower alkoxy, or R.sup.1 and R.sup.6 taken together with the atoms to which they are attached form a 6-membered ring which may contain an oxygen or sulfur atom and which may be substituted with lower alkyl; as well as pharmaceutical compositions comprising such novel compounds and the thereapeutic use thereof.

  披露了具有公式##STR1##的新型抗菌化合物，以及药学上可接受的盐、酯、酰胺和前药，其中R.sup.1选自以下组：(a)低级烷基，(b)卤代(低级烷基)，(c)低级烷基(炔基)，(d)低级环烷基，(e)低级烷基氨基，(f)含氮的芳香杂环，(g)双环烷基和(h)苯基；R.sup.2选自氢、低级烷基、药学上可接受的阳离子和前药酯基组；R.sup.3和R.sup.4独立选自氢、卤素、氨基和低级烷基；R.sup.5是含氮杂环或含氮螺环双杂环；A是N或C--R.sup.6，其中R.sup.6选自氢、卤素、低级烷基和低级烷氧基，或者R.sup.1和R.sup.6与它们所连接的原子一起形成一个可能含有氧或硫原子的6元环，该6元环可能被低级烷基取代；以及包含这些新型化合物的药物组合物及其治疗用途。
• Syntheses and antibacterial activity of novel 6-fluoro-7-(<i>gem</i>-disubstituted piperazin-1-yl)-quinolines
  作者：Daniel T. W. Chu、Akiyo K. Claiborne、Jacob J. Clement、Jacob J. Plattner

  DOI：10.1139/v92-171

  日期：1992.5.1

  A series of quinoline and naphthyridine antibacterial agents possessing an acyclic or cyclic gem-disubstituted piperazine substituent at the C-7 position have been prepared and evaluated in vitro and in vivo for antibacterial activity against a variety of Gram-positive and Gram-negative organisms. They are, however, not as active as quinolones or naphthyridines with a monosubstituted piperazine substituent at C-7. The chemical synthesis of these derivatives is also described.

  已经制备并评估了一系列含有在C-7位置带有非环状或环状的双取代哌嗪基团的喹啉和萘啶类抗菌剂，用于对多种革兰氏阳性菌和革兰氏阴性菌的体外和体内抗菌活性的研究。然而，它们并不像在C-7位置带有单取代哌嗪基团的喹诺酮或萘啶那样有效。这些衍生物的化学合成也被描述了。