benzyl 1-cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylate 2,2,2-trifluoroacetate salt

• 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: benzyl 1-cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylate 2,2,2-trifluoroacetate salt
• 英文别名: benzyl 1-cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylate trifluoroacetate；Benzyl 1-cyclopropyl-6-fluoro-4-oxo-7-piperazin-1-ylquinoline-3-carboxylate;2,2,2-trifluoroacetic acid；benzyl 1-cyclopropyl-6-fluoro-4-oxo-7-piperazin-1-ylquinoline-3-carboxylate;2,2,2-trifluoroacetic acid
• 化学式: C₂HF₃O₂*C₂₄H₂₄FN₃O₃
• 分子量: 535.495
• InChiKey: APMLJXFFBKPNBJ-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.88
• 重原子数：
  38
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.35
• 拓扑面积：
  99.2
• 氢给体数：
  2
• 氢受体数：
  12

反应信息

• 作为反应物：
  描述：

  benzyl 1-cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylate 2,2,2-trifluoroacetate salt 在 PL-HCO₃ MP StratoSphere SPE column 作用下， 以 甲醇 为溶剂， 生成 benzyl 1-cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylate
  参考文献：
  名称：

  Optimizing Solubility and Permeability of a Biopharmaceutics Classification System (BCS) Class 4 Antibiotic Drug Using Lipophilic Fragments Disturbing the Crystal Lattice

  摘要：

  Esterification was used to simultaneously increase solubility and permeability of ciprofloxacin, a biopharmaceutics classification system (BCS) class 4 drug (low solubility/low permeability) with solid-state limited solubility. Molecular flexibility was increased to disturb the crystal lattice, lower the melting point, and thereby improve the solubility, whereas lipophilicity was increased to enhance the intestinal permeability. These structural changes resulted in BCS class 1 analogues (high solubility/high permeability) emphasizing that simple medicinal chemistry may improve both these properties.

  DOI：

  10.1021/jm301721e
• 作为产物：
  描述：

  环丙沙星 在 potassium carbonate 、 sodium hydroxide 作用下， 以 四氢呋喃 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 生成 benzyl 1-cyclopropyl-6-fluoro-4-oxo-7-(piperazin-1-yl)-1,4-dihydroquinoline-3-carboxylate 2,2,2-trifluoroacetate salt
  参考文献：
  名称：

  光活化环丙沙星和胆汁酸对胆管导管生物膜的影响

  摘要：

  这项研究探讨了一种新型光活化环丙沙星对抗细菌感染和与胆道疾病相关的微生物组的潜力。它还通过结合胆汁酸和抗生素对生物膜的影响来评估治疗。评估了创新策略，以解决难以捉摸的胆管微生物组，导致与胆管导管相关的生物膜相关感染。健康的胆道系统被认为是无菌的，但胆汁微生物组可以在疾病中出现，并且这些与肝胆疾病相关。原因包括内外胆道引流导管上形成的生物膜。这些胆管导管用于非侵入性地研究原本难以捉摸的胆汁微生物组，以进行初步研究。测试了一种新型光活化抗生素对人源性致病细菌分离株和导管源性胆管微生物组的功效。此外，使用结晶紫染色、共焦激光扫描显微镜和生物膜图像分析来量化胆汁酸对生物膜抗生素治疗的影响。测试了两种针对胆汁生物膜的新方法。基于环丙沙星的光活化抗生素显示出在防止生物膜形成和降低细菌活力而不损害真核细胞方面的功效。此外，抗生素与胆汁酸（例如熊去氧胆酸）的联合治疗会轻微影响生物膜生物量，但会降低生物膜内

  DOI：

  10.1016/j.ijantimicag.2024.107086

文献信息

• [EN] BORON CONTAINING SMALL MOLECULES<br/>[FR] PETITES MOLÉCULES CONTENANT DU BORE
  申请人：ANACOR PHARMACEUTICALS INC

  公开号：WO2011037731A1

  公开（公告）日：2011-03-31

  This invention provides, among other things, novel compounds useful for treating bacterial infections, pharmaceutical compositions containing such compounds, as well as combinations of these compounds with at least one additional therapeutically effective agent.

  这项发明提供了用于治疗细菌感染的新化合物，包含这些化合物的药物组合物，以及这些化合物与至少一种其他治疗有效剂的组合。
• A Salmochelin S4-Inspired Ciprofloxacin Trojan Horse Conjugate
  作者：Thomas J. Sanderson、Conor M. Black、James W. Southwell、Ellis J. Wilde、Apurva Pandey、Reyme Herman、Gavin H. Thomas、Eszter Boros、Anne-Kathrin Duhme-Klair、Anne Routledge

  DOI：10.1021/acsinfecdis.0c00568

  日期：2020.9.11

  reduced DNA gyrase inhibition, as confirmed by in vitro DNA gyrase assays, and reduced bacterial uptake. Uptake was monitored using radiolabeling with iron-mimetic 67Ga3+, which revealed limited cellular uptake in E. coli K12. In contrast, previously reported staphyloferrin-based conjugates displayed a measurable uptake in analogous 67Ga3+ labeling studies. These results suggest that, in the design of

  一种新的环丙沙星-铁载体Trojan Horse抗菌剂是通过结合salmochelin的主要设计特征而制成的，salmochelin是一种隐身的铁载体，可通过其糖基化的邻苯二酚单元逃避哺乳动物铁丹参的捕获。对缀合物的抗微生物活性的评估表明，与铁环氧氟沙星相比，在铁充足和贫乏的条件下，沙门菌素模拟物的附着导致对两种大肠杆菌K12和Nissle 1917菌株的效力降低。该观察结果可以归因于降低的DNA促旋酶抑制作用（如体外DNA促旋酶测定法所证实）和细菌吸收降低的综合作用。使用仿铁67 Ga 3+进行放射标记监测摄取，这表明大肠杆菌K12中的细胞摄取受到限制。相反，先前报道的基于葡萄铁蛋白的缀合物在类似的67 Ga 3+标记研究中显示出可测量的摄取。这些结果表明，在特洛伊木马抗菌剂的设计中，铁载体的选择以及接头的性质和长度仍然是一个重大挑战。
• Artificial Siderophores with a Trihydroxamate‐DOTAM Scaffold Deliver Iron and Antibiotic Cargo into the Bacterial Pathogen <i>Escherichia coli</i>
  作者：Isabell Schneider、Verena Fetz、Hans‐Peter Prochnow、Mark Brönstrup

  DOI：10.1002/ijch.202300057

  日期：2023.8

  siderophore-mediated iron uptake and its use in Trojan horse conjugates. The siderophore is depicted as a black closed or open circle, and the drug as a grey-red ellipse. B) Structures of 1, 2, and 3. Iron-binding hydroxamates are shown in red, the DOTAM core in blue, and the antibiotic moiety in green. We have embarked on designing artificial siderophores as Trojan Horses, which are featured by advantages such

  介绍 多重耐药细菌感染是一个日益严重的医疗保健问题，最近被称为“无声的流行病”。1抗生素耐药性不仅会损害社区获得性感染患者成功治愈的机会，还会使化疗、器官移植或其他与感染易感性增加相关的手术等现代医学成果面临风险。新型抗药性抗生素的研发渠道薄弱且整体不足，加剧了这一问题。2对于革兰氏阴性病原体来说尤其如此，它们具有不对称的外膜，具有独特的化学成分，对于大多数小“药物样”分子来说是不可渗透的。为了获得对细菌易位更深刻的科学理解一直是大量研究工作的主题，这是寻找治疗解决方案的先决条件。3一种合理的方法是针对特洛伊木马策略中革兰氏阴性菌营养物质的入口之一（图 1）：4三价铁对于细菌生长至关重要，但由于三价铁的溶解度较低，因此在体内极为稀缺。主机的金属和竞争的铁存储系统。5因此，细菌生物合成铁载体，这是一种对铁具有高亲和力的低分子量配体，被分泌到环境中，并作为全复合物主动重新输入细菌中。6通过将抗
• Synthesis of ciprofloxacin dimers for evaluation of bacterial permeability in atypical chemical space
  作者：Audrey G. Ross、Bret M. Benton、Donovan Chin、Gianfranco De Pascale、John Fuller、Jennifer A. Leeds、Folkert Reck、Daryl L. Richie、Jason Vo、Matthew J. LaMarche

  DOI：10.1016/j.bmcl.2015.07.010

  日期：2015.9

  We describe the synthesis and evaluation of a library of variably-linked ciprofloxacin dimers. These structures unify and expand on the use of fluoroquinolones as probes throughout the antibiotic literature. A dimeric analog (19) showed enhanced inhibition of its intracellular target (DNA gyrase), and translation to antibacterial activity in whole cells was demonstrated. Overall, cell permeation was governed by physicochemical properties and bacterial type. A principal component analysis demonstrated that the dimers occupy a unique and privileged region of chemical space most similar to the macrolide class of antibiotics. (C) 2015 Elsevier Ltd. All rights reserved.
• Optimizing Solubility and Permeability of a Biopharmaceutics Classification System (BCS) Class 4 Antibiotic Drug Using Lipophilic Fragments Disturbing the Crystal Lattice
  作者：Ulrika Tehler、Jonas H. Fagerberg、Richard Svensson、Mats Larhed、Per Artursson、Christel A. S. Bergström

  DOI：10.1021/jm301721e

  日期：2013.3.28

  Esterification was used to simultaneously increase solubility and permeability of ciprofloxacin, a biopharmaceutics classification system (BCS) class 4 drug (low solubility/low permeability) with solid-state limited solubility. Molecular flexibility was increased to disturb the crystal lattice, lower the melting point, and thereby improve the solubility, whereas lipophilicity was increased to enhance the intestinal permeability. These structural changes resulted in BCS class 1 analogues (high solubility/high permeability) emphasizing that simple medicinal chemistry may improve both these properties.