1-cyclopropyl-6-fluoro-4-oxo-7-(4-propionylpiperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid | 93594-21-9

• 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-6-fluoro-4-oxo-7-(4-propionylpiperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid
• 英文别名: 7-(4-propionylpiperazin-1-yl)-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid；1-Cyclopropyl-6-fluoro-1,4-dihydro-4-oxo-7-[4-(1-oxopropyl)-1-piperazinyl]-3-quinolinecarboxylic acid；1-cyclopropyl-6-fluoro-4-oxo-7-(4-propanoylpiperazin-1-yl)quinoline-3-carboxylic acid
• CAS: 93594-21-9
• 化学式: C₂₀H₂₂FN₃O₄
• 分子量: 387.411
• InChiKey: INFGMYYEVWVBQF-UHFFFAOYSA-N

物化性质

• 熔点：
  258 °C
• 沸点：
  648.6±55.0 °C(Predicted)
• 密度：
  1.437±0.06 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  28
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  81.2
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  N-甲基哌嗪 、 1-cyclopropyl-6-fluoro-4-oxo-7-(4-propionylpiperazin-1-yl)-1,4-dihydroquinoline-3-carboxylic acid 在 O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate 作用下， 以 二氯甲烷 为溶剂， 反应 4.0h， 以59%的产率得到1-cyclopropyl-6-fluoro-3-(4-methylpiperazine-1-carbonyl)-7-(4-propionylpiperazin-1-yl)quinolin-4(1H)-one
  参考文献：
  名称：

  新型环丙沙星衍生物的设计，合成和抗分枝杆菌活性。

  摘要：

  结核病是影响人类的最致命的传染病，2016年造成约170万人死亡。致病性病原体多药耐药菌株结核分枝杆菌（Mtb）的流行增加，导致目前疗法的有效性降低，强调了迫切需要开发新的抗结核药物。在寻找此类药物时，我们研究了环丙沙星（CPX）衍生物的两个系列（类似物和杂种）。我们在此报告了这些系列在体外对人强毒性Mtb H37Rv菌株的设计，合成和生物学活性。小型丙酰基类似物11（MIC 901.6μM; SI> 61）和大型胆固醇基杂种32（MIC 90 2.0μM; SI> 6）是最活跃的衍生物，与CPX（MIC 90 1.8μM）相当。但是，活性稍弱但无细胞毒性的对-氟苄基杂种28（MIC 90 3.7μM; SI 27）对细菌的选择性比对32更具选择性。因此，CPX衍生物11和28被确定为首选的抗结核药物，需要进一步研究，包括动物模型中的分布，代谢和药代动力学参数确定以及体内活性评估。

  DOI：

  10.1111/cbdd.13534
• 作为产物：
  描述：

  环丙沙星 、 丙酸酐 在 三乙胺 作用下， 以 二氯甲烷 为溶剂， 反应 0.25h， 生成 1-cyclopropyl-6-fluoro-4-oxo-7-(4-propionylpiperazin-1-yl)-1,4-dihydroquinoline-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。
• 7-((4-Substituted)piperazin-1-yl) derivatives of ciprofloxacin: Synthesis and in vitro biological evaluation as potential antitumor agents
  作者：Joëlle Azéma、Brigitte Guidetti、Janique Dewelle、Benjamin Le Calve、Tatjana Mijatovic、Alexander Korolyov、Julie Vaysse、Myriam Malet-Martino、Robert Martino、Robert Kiss

  DOI：10.1016/j.bmc.2009.06.053

  日期：2009.8

  Ciprofloxacin (CP), an antibiotic has been shown to have antiproliferative and apoptotic activities in several cancer cell lines. Moreover, several reports have highlighted the interest of increasing the lipophilicity to improve the antitumor efficacy. These studies have led us to synthesize new CP derivatives of various lipophilicities and to evaluate their activity in five human cancer cell lines. With an easy and cost-efficient procedure, 31 7-((4-substituted)piperazin-1-yl) derivatives of CP were prepared that displayed IC50 values ranging from mu M to mM concentrations and are non-toxic in vivo in healthy mice as shown by their maximal tolerated dose (MTD) indices >80 mg/kg. Several derivatives displayed higher in vitro antitumor activity than parent CP however this was not dependent on the lipophilicity of the substituent. Among all synthesized derivatives, the most potent were 2 and 6h whose IC50 values were <= 10 mu M in three (derivative 2) or four (derivative 6h) cancer cell lines. (C) 2009 Elsevier Ltd. All rights reserved.
• 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