7-(4-(3-azido-2-hydroxypropyl)piperazin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid | 1144106-75-1

• 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-azido-2-hydroxypropyl)piperazin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
• 英文别名: 7-[4-(3-Azido-2-hydroxypropyl)piperazin-1-yl]-1-cyclopropyl-6-fluoro-4-oxoquinoline-3-carboxylic acid
• CAS: 1144106-75-1
• 化学式: C₂₀H₂₃FN₆O₄
• 分子量: 430.439
• InChiKey: YMGNWADINUWTDR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.3
• 重原子数：
  31
• 可旋转键数：
  7
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  98.7
• 氢给体数：
  2
• 氢受体数：
  10

反应信息

• 作为反应物：
  描述：

  7-(4-(3-azido-2-hydroxypropyl)piperazin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 、 在 tetrakis(actonitrile)copper(I) hexafluorophosphate 、 三乙胺 作用下， 以 水 为溶剂， 反应 0.01h， 以35%的产率得到
  参考文献：
  名称：

  共价连接的卡那霉素-环丙沙星混合抗生素作为抵抗细菌耐药性的工具。

  摘要：

  为了解决日益增长的抗生素耐药性问题，合成了一组共价连接氟喹诺酮（环丙沙星）和氨基糖苷（卡那霉素A）抗生素的12种杂合化合物，并确定了它们对革兰氏阴性和革兰氏阳性细菌的活性，包括耐药性株。杂种相对于环丙沙星具有拮抗作用，但相对于亲本卡那霉素对革兰氏阴性细菌的效力要强得多，并且克服了对氨基糖苷类的最主要的抗性机制。选定的杂种是细菌蛋白合成抑制剂的效果比亲代卡那霉素低42-640倍，而它们显示出与环丙沙星类似的对DNA促旋酶和拓扑异构酶IV酶的抑制活性。杂种在两个大肠杆菌中均显示出明显的抗性发育延迟。大肠埃希菌和枯草芽孢杆菌与单独的成分药物或其1：1混合物相比。更一般地，数据表明氨基糖苷-氟喹诺酮杂化物的拮抗组合可以导致减慢/防止耐药性出现的新化合物。

  DOI：

  10.1016/j.bmc.2017.02.068
• 作为产物：
  描述：

  环丙沙星 、 (+/-)-1-azido-3-bromo-2-propanol 在 碳酸氢钠 作用下， 以 乙腈 为溶剂， 以31%的产率得到7-(4-(3-azido-2-hydroxypropyl)piperazin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
  参考文献：
  名称：

  Conjugated antimicrobial agents

  摘要：

  本文提供了两种抗生素的抗菌结合物，展现出对抗耐药细菌的改善活性，相比单独使用每种抗生素或它们的混合物，并且基本上没有产生抗性，以及制备这些结合物的过程、含有这些结合物的组合物，以及在医疗治疗中对抗病原微生物的用途。所披露的抗菌结合物由氨基糖苷类和非核糖体活性抗生素组成。其中一些抗菌结合物是通过“click”化学方法制备的。

  公开号：

  US09149536B2

文献信息

• Design, Synthesis, and Evaluation of Novel Fluoroquinolone−Aminoglycoside Hybrid Antibiotics
  作者：Varvara Pokrovskaya、Valery Belakhov、Mariana Hainrichson、Sima Yaron、Timor Baasov

  DOI：10.1021/jm900028n

  日期：2009.4.23

  A series of new hybrid structures containing fluoroquinolone (ciprofloxacin) and aminoglycoside (neomycin) antibiotics linked via 1,2,3-triazole moiety were designed and synthesized, and their antibacterial activities were determined against both Gram-negative and Gram-positive bacteria, including resistant strains. The nature of spacers in both the ciprofloxacin and neomycin parts greatly influenced the antibacterial activity. The majority of hybrids was significantly more potent than the parent neomycin and overcame most prevalent types of resistance associated with aminoglycosides. Selected hybrids inhibited bacterial protein synthesis with the potencies similar to or better than that of neomycin and were up to 32-fold more potent inhibitors than ciprofloxacin for the fluoroquinolone targets, DNA gyrase and toposiomerase IV, indicating a balanced dual mode of action. Significant delay of resistance formation was observed in both E. coli and B. subtilis to the treatment with ciprofloxacin-neomycin hybrid in comparison to that of each drug separately or their 1: 1 mixture.
• CONJUGATED ANTIMICROBIAL AGENTS
  申请人：Technion Research & Development Foundation Ltd.

  公开号：EP2413974A1

  公开（公告）日：2012-02-08
• US8809286B2
  申请人：——

  公开号：US8809286B2

  公开（公告）日：2014-08-19
• US9149536B2
  申请人：——

  公开号：US9149536B2

  公开（公告）日：2015-10-06
• [EN] CONJUGATED ANTIMICROBIAL AGENTS<br/>[FR] AGENTS ANTIMICROBIENS CONJUGUÉS
  申请人：TECHNION RES & DEV FOUNDATION

  公开号：WO2010113151A1

  公开（公告）日：2010-10-07

  Provided herein are antimicrobial conjugates of two antibiotic agents, exhibiting improved activity also against resistant bacteria, compared to each of the agents separately or their mixture, and having substantially no resistance emerged thereagainst, as well as processes for preparation the same, compositions containing the same, and uses thereof in medical treatments against pathogenic microorganisms. The disclosed antimicrobial conjugates are composed of aminoglycosides and non-ribosomal active antibiotics. Some of the antimicrobial conjugates are prepared via "click" chemistry.