ethyl 1-cyclopropyl-7-fluoro-8-methyl-6-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylate | 173315-59-8

• 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: ethyl 1-cyclopropyl-7-fluoro-8-methyl-6-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylate
• 英文别名: Ethyl 1-cyclopropyl-7-fluoro-8-methyl-6-nitro-4-oxoquinoline-3-carboxylate
• CAS: 173315-59-8
• 化学式: C₁₆H₁₅FN₂O₅
• 分子量: 334.304
• InChiKey: UQWVYXHQUYNLHJ-UHFFFAOYSA-N

物化性质

• 沸点：
  516.7±50.0 °C(Predicted)
• 密度：
  1.463±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  3
• 重原子数：
  24
• 可旋转键数：
  4
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.38
• 拓扑面积：
  92.4
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  ethyl 1-cyclopropyl-7-fluoro-8-methyl-6-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylate 在 镍 氢气 作用下， 以 乙二醇甲醚 为溶剂， 反应 1.0h， 以92%的产率得到6-Amino-1-cyclopropyl-7-fluoro-8-methyl-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  Studies on 6-Aminoquinolones:  Synthesis and Antibacterial Evaluation of 6-Amino-8-methylquinolones

  摘要：

  The 6-aminoquinolone had previously been identified as a new class of quinolone antibacterial agents. To continue our structure-activity relationship (SAR) study in this series, novel 6-amino-8-methylquinolone derivatives have now been synthesized and evaluated for in vitro antibacterial activity. We have shown that the coupled presence of a methyl group at the C-8 position with an amino group at C-6 is effective for enhancing antibacterial activity, particularly against Gram-positive bacteria. The SARs associated with the N-1, C-6, and C-7 are discussed. The 1,2,3,4-tetrahydroisoquinolinyl derivative 19v showed the highest antibacterial activity with MIC values on Gram-positive bacteria superior to that of ciprofloxacin, especially against Staphylococcus aureus strains, including those strains which are methicillin- and ciprofloxacin-resistant.

  DOI：

  10.1021/jm950558v
• 作为产物：
  描述：

  2-chloro-4-fluoro-3-methyl-5-nitrobenzoic acid 在 氯化亚砜 、 potassium carbonate 、 三乙胺 作用下， 以 乙醚 、 乙醇 、 N,N-二甲基甲酰胺 、 甲苯 为溶剂， 反应 5.92h， 生成 ethyl 1-cyclopropyl-7-fluoro-8-methyl-6-nitro-4-oxo-1,4-dihydroquinoline-3-carboxylate
  参考文献：
  名称：

  Studies on 6-Aminoquinolones:  Synthesis and Antibacterial Evaluation of 6-Amino-8-methylquinolones

  摘要：

  The 6-aminoquinolone had previously been identified as a new class of quinolone antibacterial agents. To continue our structure-activity relationship (SAR) study in this series, novel 6-amino-8-methylquinolone derivatives have now been synthesized and evaluated for in vitro antibacterial activity. We have shown that the coupled presence of a methyl group at the C-8 position with an amino group at C-6 is effective for enhancing antibacterial activity, particularly against Gram-positive bacteria. The SARs associated with the N-1, C-6, and C-7 are discussed. The 1,2,3,4-tetrahydroisoquinolinyl derivative 19v showed the highest antibacterial activity with MIC values on Gram-positive bacteria superior to that of ciprofloxacin, especially against Staphylococcus aureus strains, including those strains which are methicillin- and ciprofloxacin-resistant.

  DOI：

  10.1021/jm950558v

文献信息

• Advantageous Use of Ionic Liquids for the Synthesis of Pharmaceutically Relevant Quinolones
  作者：Rolando Cannalire、Matteo Tiecco、Violetta Cecchetti、Raimondo Germani、Giuseppe Manfroni

  DOI：10.1002/ejoc.201800415

  日期：2018.6.22

  The use of ILs instead of DMF in the Grohe cycloaracylation for the synthesis of pharmaceutically relevant quinolones has several advantages. [TBMA][MsO] was the most favourable IL and was used in a one‐pot/three‐step procedure for the preparation of a quinolone acid by a totally green procedure. Our procedure represents an alternative approach to the industrial production of quinolones.

  在Grohe环酰化反应中使用IL代替DMF合成药物相关喹诺酮具有若干优势。[TBMA] [MsO]是最有利的IL，用于一锅/三步程序中，通过完全绿色的程序制备喹诺酮酸。我们的程序代表了喹诺酮类工业生产的替代方法。
• From 6-Aminoquinolone Antibacterials to 6-Amino-7-thiopyranopyridinylquinolone Ethyl Esters as Inhibitors of <i>Staphylococcus aureus</i> Multidrug Efflux Pumps
  作者：Marco Pieroni、Mirjana Dimovska、Jean Pierre Brincat、Stefano Sabatini、Emanuele Carosati、Serena Massari、Glenn W. Kaatz、Arnaldo Fravolini

  DOI：10.1021/jm1003304

  日期：2010.6.10

  poor substrates for NorA was investigated further. Several quinolone ester intermediates, devoid of any intrinsic antibacterial activity, were tested for their abilities to inhibit the activities of NorA (MFS family) and MepA (MATE family) S. aureus MDR efflux pumps. Selected quinolone esters were capable of inhibiting both MDR pumps more efficiently than the reference compound reserpine. Moreover, they

  硫代吡喃吡啶部分被合成为新的杂环碱基，插入选定的喹诺酮核的C-7位置，然后确定对金黄色葡萄球菌菌株的抗菌活性。选定的硫吡喃并吡啶基喹诺酮类药物显示出显着的抗菌活性，包括在gyrA和grlA中具有突变的菌株以及其他过表达NorA多药（MDR）外排泵的菌株。大多数衍生物似乎不是NorA底物。进一步研究了硫代吡喃并吡啶基取代基使这些喹诺酮类药物成为NorA不良底物的作用。测试了几种不含任何固有抗菌活性的喹诺酮酯中间体抑制NorA（MFS家族）和MepA（MATE家族）金黄色葡萄球菌MDR外排泵的活性。与参考化合物利血平相比，所选的喹诺酮酯能够更有效地抑制两种MDR泵。而且，它们还能够恢复甚至增强环丙沙星对某些基因修饰的抗金黄色葡萄球菌菌株的活性。