7-(4-decanoylpiperazin-1-yl)-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid | 1044145-99-4

• 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-decanoylpiperazin-1-yl)-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid
• 英文别名: 1-Cyclopropyl-7-(4-decanoylpiperazin-1-yl)-6-fluoro-4-oxoquinoline-3-carboxylic acid
• CAS: 1044145-99-4
• 化学式: C₂₇H₃₆FN₃O₄
• 分子量: 485.599
• InChiKey: SFYUTWWSUHXVSI-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  5.2
• 重原子数：
  35
• 可旋转键数：
  11
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.59
• 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：

  7-(4-decanoylpiperazin-1-yl)-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxoquinoline-3-carboxylic acid 、 [Ru(η6-pcym)Cl2]2 在 三乙胺 、 sodium methylate 作用下， 以 甲醇 、 氯仿 为溶剂， 反应 48.25h， 以55.4%的产率得到[Ru(η6-p-cymene)(CipA-H)Cl]
  参考文献：
  名称：

  一种新型双功能钌 (II)-芳烃复合物的抗菌环丙沙星衍生物 — 抗增殖和抗菌活性

  摘要：

  7-(4-(癸酰基)哌嗪-1-基)-环丙沙星, CipA, ( 1 ) 是抗生素环丙沙星的类似物及其钌 (II) 络合物 [Ru(η 6 - p -cymene)(CipA -H )Cl], ( 2 ) 合成了1 ·1.3H 2 O·0.6CH 3 OH和2 ·CH 3 OH·0.5H 2 O的X射线晶体结构。该配合物采用典型的伪八面体“钢琴凳”几何形状，Ru(II) π-键合到p-甲基异丙基苯环和 σ-键合到螯合的氟喹诺酮配体的一个氯原子和两个氧原子上。该复合物在低 μM 范围内具有高度细胞毒性，并且与临床药物顺铂一样对人类癌细胞系 A2780、A549、HCT116 和 PC3 有效。它对顺铂和奥沙利铂耐药细胞系也具有高度细胞毒性，表明其作用机制不同。该复合物还保留了对人结肠癌细胞系 HCT116p53 的低 μM 细胞毒性，其中肿瘤抑制基因 p53 已被敲除，这表明与该复合物相关的有效抗增殖特性与

  DOI：

  10.1016/j.jinorgbio.2016.02.018
• 作为产物：
  描述：

  正癸酸酐 、 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-decanoylpiperazin-1-yl)-1-cyclopropyl-6-fluoro-1,4-dihydro-4-oxoquinoline-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

• A new class of prophylactic metallo-antibiotic possessing potent anti-cancer and anti-microbial properties
  作者：Ziga Ude、Kevin Kavanagh、Brendan Twamley、Milan Pour、Nicholas Gathergood、Andrew Kellett、Celine J. Marmion

  DOI：10.1039/c9dt00250b

  日期：——

  human prostate carcinoma cell line (DU145) with low micromolar and, in some cases, nanomolar cytotoxicities observed. Selective targeting of Gram positive bacteria was also identified by this complex class with one lead compound having an order of magnitude greater potency against Methicillin-resistant S. aureus (MRSA) as compared to the CipA ligand. Importantly, from a clinical stand point, these complexes

  免疫功能低下的癌症患者通常处于发生感染的高风险中。需要采取标准的感染控制措施来预防感染的发生，但是在某些情况下，必须采取抗菌措施。我们已经开发了一系列创新的通式[Cu（N，N）（CipA）Cl]的金属抗生素，其中N，N代表菲配体，CipA代表临床上使用的氟喹诺酮抗生素环丙沙星的衍生物。还报道了该家族的一个成员[Cu（phen）（CipA）Cl]（其中phen为1,10-菲咯啉）的X射线晶体结构。这些复合物将具有DNA结合和DNA氧化特性的Cu-N，N-框架与具有已知抗增殖和抗微生物活性的抗生素衍生物结合为一个药物实体。7 M（bp） -1。涉及小牛胸腺DNA的生物物理研究表明，复合物可通过小沟嵌入或半嵌入DNA。所有复合物均表现出优异的核酸酶活性，DNA链断裂主要通过超氧化物和羟基自由基介导。发现该复合物对人乳腺腺癌细胞系（MCF-7）和人前列腺癌细胞系（DU145）具有低微摩尔，在某些情
• Fluoroquinolones and use thereof to treat bacterial infections
  申请人：UNIVERSITÉ PIERRE ET MARIE CURIE—PARIS 6 (UPMC)

  公开号：US10087165B2

  公开（公告）日：2018-10-02

  The present invention relates to novel fluoroquinolones, pharmaceutical compositions or medicament containing them and use thereof to treat bacterial infection.

  本发明涉及新型氟喹诺酮类药物、药物组合物或含有它们的药物以及使用它们治疗细菌感染。
• 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.
• NOVEL FLUOROQUINOLONES AND USE THEREOF TO TREAT BACTERIAL INFECTIONS
  申请人：Université Pierre et Marie Curie - Paris 6 (UPMC)

  公开号：EP3157911A1

  公开（公告）日：2017-04-26
• [EN] NOVEL FLUOROQUINOLONES AND USE THEREOF TO TREAT BACTERIAL INFECTIONS<br/>[FR] NOUVEAUX FLUOROQUINOLONES ET LEUR UTILISATION POUR TRAITER DES INFECTIONS BACTÉRIENNES
  申请人：UNIVERSITÉ PIERRE ET MARIE CURIE PARIS 6 UPMC

  公开号：WO2015193454A1

  公开（公告）日：2015-12-23

  The present invention relates to novel fluoroquinolones, pharmaceutical compositions or medicament containing them and use thereof to treat bacterial infection.