1-Cyclopropyl-7-((S)-4-{4-[4-(3-ethyl-4-methyl-phenylamino)-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-butyl}-3-methyl-piperazin-1-yl)-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid ethyl ester | 1026866-47-6

• 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: 1-Cyclopropyl-7-((S)-4-{4-[4-(3-ethyl-4-methyl-phenylamino)-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-butyl}-3-methyl-piperazin-1-yl)-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid ethyl ester
• 英文别名: ethyl 1-cyclopropyl-7-[(3S)-4-[4-[6-(3-ethyl-4-methylanilino)-2,4-dioxo-1H-pyrimidin-3-yl]butyl]-3-methylpiperazin-1-yl]-6-fluoro-4-oxoquinoline-3-carboxylate
• CAS: 1026866-47-6
• 化学式: C₃₇H₄₅FN₆O₅
• 分子量: 672.8
• InChiKey: XFZLZHIWQVKHMV-DEOSSOPVSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.8
• 重原子数：
  49
• 可旋转键数：
  13
• 环数：
  6.0
• sp3杂化的碳原子比例：
  0.46
• 拓扑面积：
  115
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  1-Cyclopropyl-7-((S)-4-{4-[4-(3-ethyl-4-methyl-phenylamino)-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-butyl}-3-methyl-piperazin-1-yl)-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid ethyl ester 在 lithium hydroxide 作用下， 以 甲醇 为溶剂， 生成 1-Cyclopropyl-7-((S)-4-{4-[4-(3-ethyl-4-methyl-phenylamino)-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-butyl}-3-methyl-piperazin-1-yl)-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid
  参考文献：
  名称：

  Hybrid Antibacterials. DNA Polymerase−Topoisomerase Inhibitors

  摘要：

  Novel Gram-positive (Gram+) antibacterial compounds consisting of a DNA polymerase IIIC (pol IIIC) inhibitor covalently connected to a topoisomerase/gyrase inhibitor are described. Specifically, 3-substituted 6-(3-ethyl-4-methylanilino)uracils (EMAUs) in which the 3-substituent is a fluoroquinolone moiety (FQ) connected by various linkers were synthesized. The resulting "AU-FQ" hybrid compounds were significantly more potent than the parent EMAU compounds as inhibitors of pol IIIC and were up to 64-fold more potent as antibacterials in vitro against Gram+ bacteria. The hybrids inhibited the FQ targets, topoisomerase IV and gyrase, with potencies similar to norfloxacin but 10-fold lower than newer agents, for example, ciprofloxacin and sparfloxacin. Representative hybrids protected mice from lethal Staphylococcus aureus infection after intravenous dosing, and one compound showed protective effect against several antibiotic-sensitive and -resistant Gram+ infections in mice. The AU-FQ hybrids are a promising new family of antibacterials for treatment of antibiotic-resistant Gram+ infections.

  DOI：

  10.1021/jm0510023
• 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 碳酸氢钠 作用下， 以 二甲基亚砜 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 1-Cyclopropyl-7-((S)-4-{4-[4-(3-ethyl-4-methyl-phenylamino)-2,6-dioxo-3,6-dihydro-2H-pyrimidin-1-yl]-butyl}-3-methyl-piperazin-1-yl)-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid ethyl ester
  参考文献：
  名称：

  Hybrid Antibacterials. DNA Polymerase−Topoisomerase Inhibitors

  摘要：

  Novel Gram-positive (Gram+) antibacterial compounds consisting of a DNA polymerase IIIC (pol IIIC) inhibitor covalently connected to a topoisomerase/gyrase inhibitor are described. Specifically, 3-substituted 6-(3-ethyl-4-methylanilino)uracils (EMAUs) in which the 3-substituent is a fluoroquinolone moiety (FQ) connected by various linkers were synthesized. The resulting "AU-FQ" hybrid compounds were significantly more potent than the parent EMAU compounds as inhibitors of pol IIIC and were up to 64-fold more potent as antibacterials in vitro against Gram+ bacteria. The hybrids inhibited the FQ targets, topoisomerase IV and gyrase, with potencies similar to norfloxacin but 10-fold lower than newer agents, for example, ciprofloxacin and sparfloxacin. Representative hybrids protected mice from lethal Staphylococcus aureus infection after intravenous dosing, and one compound showed protective effect against several antibiotic-sensitive and -resistant Gram+ infections in mice. The AU-FQ hybrids are a promising new family of antibacterials for treatment of antibiotic-resistant Gram+ infections.

  DOI：

  10.1021/jm0510023