1-Cyclopropyl-7-[3-(diethylcarbamoyloxymethyl)piperazin-1-yl]-6-fluoro-4-oxo-quinoline-3-carboxylic acid | 1422285-32-2

• 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: 1-Cyclopropyl-7-[3-(diethylcarbamoyloxymethyl)piperazin-1-yl]-6-fluoro-4-oxo-quinoline-3-carboxylic acid
• 英文别名: 1-cyclopropyl-7-[3-(diethylcarbamoyloxymethyl)piperazin-1-yl]-6-fluoro-4-oxoquinoline-3-carboxylic acid
• CAS: 1422285-32-2
• 化学式: C₂₃H₂₉FN₄O₅
• 分子量: 460.505
• InChiKey: NCXYCPHKIPJSIH-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.4
• 重原子数：
  33
• 可旋转键数：
  8
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.52
• 拓扑面积：
  102
• 氢给体数：
  2
• 氢受体数：
  9

反应信息

• 作为产物：
  描述：

  1-环丙基-6,7-二氟-4-氧代-1,4-二氢喹啉-3-羧酸乙酯 在 三氟化硼乙醚 、 potassium carbonate 、 三乙胺 作用下， 以 四氢呋喃 、 乙腈 为溶剂， 生成 1-Cyclopropyl-7-[3-(diethylcarbamoyloxymethyl)piperazin-1-yl]-6-fluoro-4-oxo-quinoline-3-carboxylic acid
  参考文献：
  名称：

  Synthesis of gatifloxacin derivatives and their biological activities against Mycobacterium leprae and Mycobacterium tuberculosis

  摘要：

  Novel 3'-piperazinyl derivatives of the 8-hydrogeno and 8-methoxy-6-fluoro-1-cyclopropyl-4quinolone-3-carboxylic acid scaffolds were designed, synthesized and characterized by H-1, C-13 and F-19 NMR, and HRMS. The activity of these derivatives against pathogenic mycobacteria (M. leprae and M. tuberculosis), wild-type (WT) strains or strains harboring mutations implicated in quinolone resistance, were determined by measuring drug concentrations inhibiting cell growth (MIC) and/or DNA supercoiling by DNA gyrase (IC50), or inducing 25% DNA cleavage by DNA gyrase (CC25). Compound 4 (with a methoxy in R-8 and a secondary carbamate in R-3') and compound 5 (with a hydrogen in R-8 and an ethyl ester in R-3') displayed biological activities close to those of ofloxacin but inferior to those of gatifloxacin and moxifloxacin against M. tuberculosis and M. leprae WT DNA gyrases, whereas all of the compounds were less active in inhibiting M. tuberculosis growth and M. leprae mutant DNA gyrases. Since R-3' substitutions have been poorly investigated previously, our results may help to design new quinolone derivatives in the future. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.12.011

文献信息

• Synthesis of gatifloxacin derivatives and their biological activities against Mycobacterium leprae and Mycobacterium tuberculosis
  作者：Catherine Gomez、Prishila Ponien、Nawal Serradji、Aazdine Lamouri、Alix Pantel、Estelle Capton、Vincent Jarlier、Guillaume Anquetin、Alexandra Aubry

  DOI：10.1016/j.bmc.2012.12.011

  日期：2013.2

  Novel 3'-piperazinyl derivatives of the 8-hydrogeno and 8-methoxy-6-fluoro-1-cyclopropyl-4quinolone-3-carboxylic acid scaffolds were designed, synthesized and characterized by H-1, C-13 and F-19 NMR, and HRMS. The activity of these derivatives against pathogenic mycobacteria (M. leprae and M. tuberculosis), wild-type (WT) strains or strains harboring mutations implicated in quinolone resistance, were determined by measuring drug concentrations inhibiting cell growth (MIC) and/or DNA supercoiling by DNA gyrase (IC50), or inducing 25% DNA cleavage by DNA gyrase (CC25). Compound 4 (with a methoxy in R-8 and a secondary carbamate in R-3') and compound 5 (with a hydrogen in R-8 and an ethyl ester in R-3') displayed biological activities close to those of ofloxacin but inferior to those of gatifloxacin and moxifloxacin against M. tuberculosis and M. leprae WT DNA gyrases, whereas all of the compounds were less active in inhibiting M. tuberculosis growth and M. leprae mutant DNA gyrases. Since R-3' substitutions have been poorly investigated previously, our results may help to design new quinolone derivatives in the future. (C) 2012 Elsevier Ltd. All rights reserved.