7-[4-(3-methyl-butyryl)-piperazin-1-yl]-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-quinoline-3-carboxylic acid

• 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-(3-methyl-butyryl)-piperazin-1-yl]-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-quinoline-3-carboxylic acid
• 英文别名: 1-Cyclopropyl-6-fluoro-7-[4-(3-methylbutanoyl)piperazin-1-yl]-4-oxoquinoline-3-carboxylic acid
• 化学式: C₂₂H₂₆FN₃O₄
• 分子量: 415.465
• InChiKey: XHBXNVODDZODTI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.4
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  81.2
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为产物：
  描述：

  异戊酸酐 、 环丙沙星 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.25h， 生成 7-[4-(3-methyl-butyryl)-piperazin-1-yl]-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-quinoline-3-carboxylic acid
  参考文献：
  名称：

  Studies on the antimicrobial properties of N-acylated ciprofloxacins

  摘要：

  Fluoroquinolone antibiotics have been a mainstay in the treatment of bacterial diseases. The most notable representative, ciprofloxacin, possesses potent antimicrobial activity; however, a rise in resistance to this agent necessitates development of novel derivatives to prolong the clinical lifespan of these antibiotics. Herein we have synthesized and analyzed the antimicrobial properties of a library of N-acylated ciprofloxacin analogues. We find that these compounds are broadly effective against Gram-positive and Gram-negative bacteria, with many proving more effective than the parental drug, and several possessing MICs <= 1.0 mu g/ml against methicillin-resistant Staphylococcus aureus and Bartonella species. An analysis of spontaneous mutation frequencies reveals very low potential for resistance in MRSA compared to existing fluoroquinolones. Mode of action profiling reveals that modification of the piperazinyl nitrogen by acylation does not alter the effect of these molecules towards their bacterial target. We also present evidence that these N-acylated compounds are highly effective at killing intracellular bacteria, suggesting the suitability of these antibiotics for therapeutic treatment. (c) 2012 Published by Elsevier

  DOI：

  10.1016/j.bmcl.2012.05.026

文献信息

• Chinoloncarbonsäuren, Verfahren zu ihrer Herstellung sowie diese enthaltende antibakterielle Mittel
  申请人：BAYER AG

  公开号：EP0117473A1

  公开（公告）日：1984-09-05

  Chinoloncarbonsäuren der allgemeinen Formel mit den in der Beschreibung angegebenen Bedeutungen von X und R1-R5 haben gute antibakterielle Wirkung und sollen als Wirkstoffe für Arzneimittel verwendet werden.

  通式中的喹啉羧酸（X 和 R1-R5 的含义见说明）具有良好的抗菌活性，可用作药物的活性成分。
• Bakterizide Mittel auf Chinoloncarbonsäure-Basis
  申请人：BAYER AG

  公开号：EP0121727A1

  公开（公告）日：1984-10-17

  Die Erfindung betrifft die bakterizide Verwendung von neuen 1-Cyclopropyl-1,4-dihydro-4-oxo-3-chinolincarbonsäure-Derivaten der Formel (I) in der R', R2; R3, R", R5 und X die in der Beschreibung gegebene Bedeutung haben.

  本发明涉及式 (I) 的新 1-环丙基-1,4-二氢-4-氧代-3-喹啉羧酸衍生物的杀菌用途 其中 R'、R2；R3、R"、R5 和 X 具有描述中给出的含义。
• US4559341A
  申请人：——

  公开号：US4559341A

  公开（公告）日：1985-12-17
• Studies on the antimicrobial properties of N-acylated ciprofloxacins
  作者：Ryan Cormier、Whittney N. Burda、Lacey Harrington、Jordan Edlinger、Karthik M. Kodigepalli、John Thomas、Rebecca Kapolka、Glen Roma、Burt E. Anderson、Edward Turos、Lindsey N. Shaw

  DOI：10.1016/j.bmcl.2012.05.026

  日期：2012.10

  Fluoroquinolone antibiotics have been a mainstay in the treatment of bacterial diseases. The most notable representative, ciprofloxacin, possesses potent antimicrobial activity; however, a rise in resistance to this agent necessitates development of novel derivatives to prolong the clinical lifespan of these antibiotics. Herein we have synthesized and analyzed the antimicrobial properties of a library of N-acylated ciprofloxacin analogues. We find that these compounds are broadly effective against Gram-positive and Gram-negative bacteria, with many proving more effective than the parental drug, and several possessing MICs <= 1.0 mu g/ml against methicillin-resistant Staphylococcus aureus and Bartonella species. An analysis of spontaneous mutation frequencies reveals very low potential for resistance in MRSA compared to existing fluoroquinolones. Mode of action profiling reveals that modification of the piperazinyl nitrogen by acylation does not alter the effect of these molecules towards their bacterial target. We also present evidence that these N-acylated compounds are highly effective at killing intracellular bacteria, suggesting the suitability of these antibiotics for therapeutic treatment. (c) 2012 Published by Elsevier