ethyl 1-(2,4-difluorophenyl)-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinoline-carboxylate | 114214-48-1

• 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: ethyl 1-(2,4-difluorophenyl)-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinoline-carboxylate
• 英文别名: Ethyl 1-(2,4-difluorophenyl)-6,7-difluoro-8-methoxy-1,4-dihydro-4-oxoquinoline-3-carboxylate；Ethyl 1-(2,4-difluorophenyl)-6,7-difluoro-8-methoxy-4-oxoquinoline-3-carboxylate
• CAS: 114214-48-1
• 化学式: C₁₉H₁₃F₄NO₄
• 分子量: 395.31
• InChiKey: KWAGMPYFVMXYGR-UHFFFAOYSA-N

物化性质

• 熔点：
  186-187 °C
• 沸点：
  499.3±45.0 °C(Predicted)
• 密度：
  1.441±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.1
• 重原子数：
  28
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.16
• 拓扑面积：
  55.8
• 氢给体数：
  0
• 氢受体数：
  9

反应信息

• 作为反应物：
  描述：

  ethyl 1-(2,4-difluorophenyl)-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinoline-carboxylate 在 三氟化硼乙醚 作用下， 以 四氢呋喃 为溶剂， 反应 48.0h， 以78%的产率得到(1-(2,4-difluorophenyl)-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinoline-carboxylato-O3,O4)difluoro-boron
  参考文献：
  名称：

  Design, synthesis and activity against Toxoplasma gondii, Plasmodium spp., and Mycobacterium tuberculosis of new 6-fluoroquinolones

  摘要：

  This paper reports on the rational design of a series of new 6-fluoroquinolones by QSAR analysis against Toxoplasma (T.) gondii, their synthesis, their biological evaluation against T. gondii and Plasmodium (P.) spp., and their effect on Mycobacterium (M.) tuberculosis DNA gyrase and growth inhibition. Of the 12 computer-designed 8-ethyl(or methoxy)- and 5-ethyl-8-methoxy-6-fluoroquinolones predicted to be active against T. gondii, we succeeded in the synthesis of four 6-fluoro-8-methoxy-quinolones. The four 6-fluoro-8-methoxy-quinolones are active on T. gondii but only one is as active as predicted. One of these four compounds appears to be an antiparasitical drug of great potential with inhibitory activities comparable to or higher than that of trovafloxacin, gatifloxacin, and moxifloxacin. They also inhibit DNA supercoiling by M. tuberculosis gyrase with an efficiency comparable to that of the most active quinolones but are poor inhibitors of M. tuberculosis growth. (c) 2006 Elsevier Masson SAS. All rights reserved.

  DOI：

  10.1016/j.ejmech.2006.07.003
• 作为产物：
  描述：

  2,4-二氟苯胺 在 potassium carbonate 作用下， 以 乙醚 、 乙醇 、 N,N-二甲基甲酰胺 为溶剂， 反应 8.0h， 生成 ethyl 1-(2,4-difluorophenyl)-6,7-difluoro-1,4-dihydro-8-methoxy-4-oxo-3-quinoline-carboxylate
  参考文献：
  名称：

  新型氟喹诺酮类化合物的合成及其对弓形虫和疟原虫的体外活性评估。

  摘要：

  描述了四种新的计算机设计的氟喹诺酮的合成，这些合成的氟喹诺酮已通过QSAR分析预测对弓形虫原虫具有活性。这些化合物在体外对弓形虫有抑制作用。这些化合物之一具有与曲伐沙星相当的高活性。它结合了加替沙星或莫西沙星的基本环丙基喹啉结构与托伐沙星的C-7 6-氨基-3-氮杂双环[3.1.0]己基侧链。这四种化合物即使在高浓度下也对恶性疟原虫的血液阶段具有抑制作用。这些结果证实了喹诺酮类药物具有抗T的潜力。刚地和抗疟药，但也表明不能可靠地扩展刚地弓形虫的QSAR模型来筛选抗疟活性。

  DOI：

  10.1016/j.bmcl.2004.03.070

文献信息

• Quinoline-3-carboxylic acid derivatives, their preparation and use
  申请人：Sankyo Company Limited

  公开号：EP0241206A2

  公开（公告）日：1987-10-14

  Compounds of formula (I): (in which R1 is alkoxy, R is alkyl, haloalkyl, alkylammo, cycloalkyl or optionally substituted phenyl, X is chlorine or fluorine and Y is selected from certain specific heterocycles) have excellent antibacterial activity. They may be prepared by introducing the group represented by Y into the corresponding compound in which Y is replaced by a halogen atom.

  式(I)化合物： (其中 R1 为烷氧基，R 为烷基、卤代烷基、烷基酰胺基、环烷基或任选取代的苯基，X 为氯或氟，Y 选自某些特定杂环）具有极佳的抗菌活性。它们可以通过将 Y 所代表的基团引入相应的化合物中来制备，其中 Y 被卤素原子取代。
• US4997943A
  申请人：——

  公开号：US4997943A

  公开（公告）日：1991-03-05
• Synthesis of new fluoroquinolones and evaluation of their in vitro activity on Toxoplasma gondii and Plasmodium spp
  作者：G. Anquetin、M. Rouquayrol、N. Mahmoudi、M. Santillana-Hayat、R. Gozalbes、J. Greiner、K. Farhati、F. Derouin、R. Guedj、P. Vierling

  DOI：10.1016/j.bmcl.2004.03.070

  日期：2004.6

  6-amino-3-azabicyclo[3.1.0]hexyl side chain of trovafloxacin. The four compounds are also inhibitory for blood stages of Plasmodium falciparum though at high concentration. These results confirm the potential of quinolones as anti-T. gondii and antimalarial drugs but also show that the QSAR models for T. gondii cannot be reliably extended for screening antimalarial activity.

  描述了四种新的计算机设计的氟喹诺酮的合成，这些合成的氟喹诺酮已通过QSAR分析预测对弓形虫原虫具有活性。这些化合物在体外对弓形虫有抑制作用。这些化合物之一具有与曲伐沙星相当的高活性。它结合了加替沙星或莫西沙星的基本环丙基喹啉结构与托伐沙星的C-7 6-氨基-3-氮杂双环[3.1.0]己基侧链。这四种化合物即使在高浓度下也对恶性疟原虫的血液阶段具有抑制作用。这些结果证实了喹诺酮类药物具有抗T的潜力。刚地和抗疟药，但也表明不能可靠地扩展刚地弓形虫的QSAR模型来筛选抗疟活性。
• Design, synthesis and activity against Toxoplasma gondii, Plasmodium spp., and Mycobacterium tuberculosis of new 6-fluoroquinolones
  作者：Guillaume Anquetin、Jacques Greiner、Nassira Mahmoudi、Maud Santillana-Hayat、Rafael Gozalbes、Khemais Farhati、Francis Derouin、Alexandra Aubry、Emmanuelle Cambau、Pierre Vierling

  DOI：10.1016/j.ejmech.2006.07.003

  日期：2006.12

  This paper reports on the rational design of a series of new 6-fluoroquinolones by QSAR analysis against Toxoplasma (T.) gondii, their synthesis, their biological evaluation against T. gondii and Plasmodium (P.) spp., and their effect on Mycobacterium (M.) tuberculosis DNA gyrase and growth inhibition. Of the 12 computer-designed 8-ethyl(or methoxy)- and 5-ethyl-8-methoxy-6-fluoroquinolones predicted to be active against T. gondii, we succeeded in the synthesis of four 6-fluoro-8-methoxy-quinolones. The four 6-fluoro-8-methoxy-quinolones are active on T. gondii but only one is as active as predicted. One of these four compounds appears to be an antiparasitical drug of great potential with inhibitory activities comparable to or higher than that of trovafloxacin, gatifloxacin, and moxifloxacin. They also inhibit DNA supercoiling by M. tuberculosis gyrase with an efficiency comparable to that of the most active quinolones but are poor inhibitors of M. tuberculosis growth. (c) 2006 Elsevier Masson SAS. All rights reserved.