7-(4-(2-(3-(4-methoxyphenyl)furan-2(5H)-one-4-yloxy)ethyl)piperazin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid | 1514777-94-6

• 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: 7-(4-(2-(3-(4-methoxyphenyl)furan-2(5H)-one-4-yloxy)ethyl)piperazin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
• 英文别名: 1-cyclopropyl-6-fluoro-7-[4-[2-[[4-(4-methoxyphenyl)-5-oxo-2H-furan-3-yl]oxy]ethyl]piperazin-1-yl]-4-oxoquinoline-3-carboxylic acid
• CAS: 1514777-94-6
• 化学式: C₃₀H₃₀FN₃O₇
• 分子量: 563.583
• InChiKey: FWFKAPLWSGTEFG-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  0.7
• 重原子数：
  41
• 可旋转键数：
  9
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  109
• 氢给体数：
  1
• 氢受体数：
  11

反应信息

• 作为产物：
  描述：

  (4-Methoxy-phenyl)-acetic acid ethoxycarbonylmethyl ester 在 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 丙酮 为溶剂， 生成 7-(4-(2-(3-(4-methoxyphenyl)furan-2(5H)-one-4-yloxy)ethyl)piperazin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
  参考文献：
  名称：

  Novel 3-arylfuran-2(5H)-one-fluoroquinolone hybrid: Design, synthesis and evaluation as antibacterial agent

  摘要：

  3-Arylfuran-2(5H)-one, a novel antibacterial pharmacophore targeting tyrosyl-tRNA synthetase (TyrRS), was hybridized with the clinically used fluoroquinolones to give a series of novel multi-target antimicrobial agents. Thus, twenty seven 3-arylfuran-2(5H)-one-fluoroquinolone hybrids were synthesized and evaluated for their antimicrobial activities. Some of the hybrids exhibited merits from both parents, displaying a broad spectrum of activity against resistant strains including both Gram-negative and Gram-positive bacteria. The most potent compound (11) in antibacterial assay shows MIC50 of 0.11μg/mL against Multiple drug resistant Escherichia coli, being about 51-fold more potent than ciprofloxacin. The enzyme assays reveal that 11 is a potent multi-target inhibitor with IC50 of 1.15±0.07μM against DNA gyrase and 0.12±0.04μM against TyrRS, respectively. Its excellent inhibitory activities against isolated enzymes and intact cells strongly suggest that 11 deserves to further research as a novel antibiotic.

  DOI：

  10.1016/j.bmc.2014.05.018

文献信息

• Novel 3-arylfuran-2(5H)-one-fluoroquinolone hybrid: Design, synthesis and evaluation as antibacterial agent
  作者：Xu-Dong Wang、Wei Wei、Peng-Fei Wang、Yun-Tao Tang、Rui-Cheng Deng、Biao Li、Sha-Sha Zhou、Jing-Wen Zhang、Lei Zhang、Zhu-Ping Xiao、Hui Ouyang、Hai-Liang Zhu

  DOI：10.1016/j.bmc.2014.05.018

  日期：2014.7

  3-Arylfuran-2(5H)-one, a novel antibacterial pharmacophore targeting tyrosyl-tRNA synthetase (TyrRS), was hybridized with the clinically used fluoroquinolones to give a series of novel multi-target antimicrobial agents. Thus, twenty seven 3-arylfuran-2(5H)-one-fluoroquinolone hybrids were synthesized and evaluated for their antimicrobial activities. Some of the hybrids exhibited merits from both parents, displaying a broad spectrum of activity against resistant strains including both Gram-negative and Gram-positive bacteria. The most potent compound (11) in antibacterial assay shows MIC50 of 0.11μg/mL against Multiple drug resistant Escherichia coli, being about 51-fold more potent than ciprofloxacin. The enzyme assays reveal that 11 is a potent multi-target inhibitor with IC50 of 1.15±0.07μM against DNA gyrase and 0.12±0.04μM against TyrRS, respectively. Its excellent inhibitory activities against isolated enzymes and intact cells strongly suggest that 11 deserves to further research as a novel antibiotic.