1-ethyl-6-fluoro-1,4-dihydro-7-methyl-4-oxo-1,8-naphthyridine-3-carboxylic acid | 99726-90-6

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氮杂萘
• 英文名称: 1-ethyl-6-fluoro-1,4-dihydro-7-methyl-4-oxo-1,8-naphthyridine-3-carboxylic acid
• 英文别名: nalidixic acid；1-Ethyl-6-fluoro-4-keto-7-methyl-1,8-naphthyridine-3-carboxylic acid；1-ethyl-6-fluoro-7-methyl-4-oxo-1,8-naphthyridine-3-carboxylic acid
• CAS: 99726-90-6
• 化学式: C₁₂H₁₁FN₂O₃
• 分子量: 250.229
• InChiKey: PBOFAIFJAUDXEA-UHFFFAOYSA-N

物化性质

• 熔点：
  252-254 °C
• 沸点：
  422.4±45.0 °C(Predicted)
• 密度：
  1.400±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.5
• 重原子数：
  18
• 可旋转键数：
  2
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.25
• 拓扑面积：
  70.5
• 氢给体数：
  1
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1-ethyl-6-fluoro-1,4-dihydro-7-methyl-4-oxo-1,8-naphthyridine-3-carboxylic acid 在 sodium hydroxide 、 氯化亚砜 、 三氯氧磷 作用下， 反应 9.67h， 生成 依诺沙星杂质3
  参考文献：
  名称：

  有效合成6-氟萘啶酸并将其转化为依诺沙星

  摘要：

  通过高效方法大量制备了1-乙基-6-氟-1,4-二氢-7-甲基-4-氧代-1,8-萘啶-3-羧酸（8）。依次将其降解，得到7-氯-1-乙基-6-氟-1,4-二氢-4-氧代-1,8-萘啶-3-羧酸（11）。该中间体已经与哌嗪反应得到已知的抗菌剂依诺沙星（12）。

  DOI：

  10.1002/jhet.5570240139
• 作为产物：
  描述：

  2-氨基-5-氟-6-甲基吡啶 在 sodium hydroxide 、 potassium carbonate 作用下， 以 乙醇 、 N,N-二甲基甲酰胺 、 xylene 为溶剂， 反应 25.5h， 生成 1-ethyl-6-fluoro-1,4-dihydro-7-methyl-4-oxo-1,8-naphthyridine-3-carboxylic acid
  参考文献：
  名称：

  有效合成6-氟萘啶酸并将其转化为依诺沙星

  摘要：

  通过高效方法大量制备了1-乙基-6-氟-1,4-二氢-7-甲基-4-氧代-1,8-萘啶-3-羧酸（8）。依次将其降解，得到7-氯-1-乙基-6-氟-1,4-二氢-4-氧代-1,8-萘啶-3-羧酸（11）。该中间体已经与哌嗪反应得到已知的抗菌剂依诺沙星（12）。

  DOI：

  10.1002/jhet.5570240139

文献信息

• New structure-activity relationships of the quinolone antibacterials using the target enzyme. The development and application of a DNA gyrase assay
  作者：John M. Domagala、Lori Doyle Hanna、Carl L. Heifetz、Marland P. Hutt、Thomas F. Mich、Joseph P. Sanchez、Marjorie Solomon

  DOI：10.1021/jm00153a015

  日期：1986.3

  A series of 60 newly synthesized and known quinolone antibacterials, including quinoline- and 1,8-naphthyridine-3-carboxylic acids, pyrido[2,3-d]pyrimidine-6-carboxylic acids, and some monocyclic 4-pyridone-3-carboxylic acids, were tested and compared in a newly established, easy to perform, DNA gyrase assay. The results were correlated with minimum inhibitory concentrations (MICs) against a variety of organisms. Among the known quinolones were 14 clinically significant drugs (oxolinic acid, norfloxacin, ciprofloxacin, enoxacin, etc.) which were used as standards and compared side-by-side. The study focused on the changes in DNA gyrase inhibition brought about by certain features of the molecules, namely, the C6-fluorine or the nature of the C7 substituent. The intrinsic gyrase inhibition of the fused parent rings, quinoline vs. naphthyridine vs. pyrido[2,3-d]pyrimidine, was also explored. In all cases, loss of enzyme inhibition produced poor MICs, but some compounds with good DNA gyrase inhibition did not correspondingly inhibit bacterial growth. Possible explanations for this phenomena and the benefits of a DNA gyrase-MIC strategy for developing future structure-activity relationships are discussed.
• SANCHEZ J. P.; ROGOWSKI J. W., J. HETEROCYCL. CHEM., 24,(1987) N 1, 215-217
  作者：SANCHEZ J. P.、 ROGOWSKI J. W.

  DOI：——

  日期：——
• An efficient synthesis of 6-fluoronalidixic acid and its conversion to enoxacin
  作者：Joseph P. Sanchez、John W. Rogowski

  DOI：10.1002/jhet.5570240139

  日期：1987.1

  1-Ethyl-6-fluoro-1,4-dihydro-7-methyl-4-oxo-1,8-naphthyridine-3-carboxylic acid (8) has been prepared in large quantities by a highly efficient process. It has in turn been degraded to give 7-chloro-1-ethyl-6-fluoro-1,4-dihydro-4-oxo-1,8-naphthyridine-3-carboxylic acid (11). This intermediate has been reacted with piperazine to give the known antibacterial agent, enoxacin (12).

  通过高效方法大量制备了1-乙基-6-氟-1,4-二氢-7-甲基-4-氧代-1,8-萘啶-3-羧酸（8）。依次将其降解，得到7-氯-1-乙基-6-氟-1,4-二氢-4-氧代-1,8-萘啶-3-羧酸（11）。该中间体已经与哌嗪反应得到已知的抗菌剂依诺沙星（12）。