7-(4-(4-(chloromethyl)benzyl)piperazin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid | 599171-74-1

• 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-(4-(chloromethyl)benzyl)piperazin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
• 英文别名: 7-[4-[[4-(Chloromethyl)phenyl]methyl]piperazin-1-yl]-1-cyclopropyl-6-fluoro-4-oxoquinoline-3-carboxylic acid
• CAS: 599171-74-1
• 化学式: C₂₅H₂₅ClFN₃O₃
• 分子量: 469.943
• InChiKey: XMCIJPWXPOLAGR-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  33
• 可旋转键数：
  6
• 环数：
  5.0
• sp3杂化的碳原子比例：
  0.36
• 拓扑面积：
  64.1
• 氢给体数：
  1
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  6-chloronorharmane 、 7-(4-(4-(chloromethyl)benzyl)piperazin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid 以 异丙醇 为溶剂， 反应 12.0h， 以48%的产率得到2-{4-[4-(3-Carboxy-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-quinolin-7-yl)-piperazin-1-ylmethyl]-benzyl}-6-chloro-9H-β-carbolin-2-ium; chloride
  参考文献：
  名称：

  Potent Algicides Based on the Cyanobacterial Alkaloid Nostocarboline

  摘要：

  Nostocarboline and seven derivatives were prepared and displayed minimal inhibitory concentration (MIC) values >= 100 nM against the growth of Microcystis aeruginosa PCC 7806, Synechococcus PCC 6911, and Kirchneriella contorta SAG 11.81, probably via the inhibition of photosynthesis. The natural product hybrid nostocarboline/ciprofloxacin displayed additional antibacterial activity against several Gram-negative bacteria (MICs >= 0.7 mu M). Nostocarboline can thus be considered a potent, selective, readily available, natural algicide.

  DOI：

  10.1021/ol052968b
• 作为产物：
  描述：

  环丙沙星 、 1,4-对二氯苄 在 碳酸氢钠 作用下， 以 N,N-二甲基甲酰胺 、 乙腈 为溶剂， 反应 24.0h， 以70%的产率得到7-(4-(4-(chloromethyl)benzyl)piperazin-1-yl)-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydroquinoline-3-carboxylic acid
  参考文献：
  名称：

  通过端基将环丙沙星与聚（2-恶唑啉）和聚乙二醇共轭

  摘要：

  将抗生素环丙沙星（CIP）共价连接到聚（2-甲基恶唑啉）（PMOx），聚（2-乙基恶唑啉）（PEtOx）和聚乙二醇（PEG）的链端，并测试这些缀合物的抗菌活性用于金黄色葡萄球菌，变形链球菌，大肠杆菌，铜绿假单胞菌和肺炎克雷泽菌。结合物的化学结构由1证明1 H NMR和电子喷雾电离质谱。PMOx和CIP的直接偶联导致较低的抗菌活性。通过间隔基的偶联提供了分子量依赖性的活性，其摩尔最小抑制浓度甚至高于原始CIP的摩尔抑制浓度。结合物的抗菌活性按PMOx

  DOI：

  10.1021/acs.bioconjchem.5b00393

文献信息

• Insights into the Kinetics of the Resistance Formation of Bacteria against Ciprofloxacin Poly(2-methyl-2-oxazoline) Conjugates
  作者：Martin Schmidt、Alina Romanovska、Youssef Wolf、Thanh-Duong Nguyen、Anna Krupp、Hannah L. Tumbrink、Jonas Lategahn、Jan Volmer、Daniel Rauh、Stephan Luetz、Christian Krumm、Joerg C. Tiller

  DOI：10.1021/acs.bioconjchem.8b00361

  日期：2018.8.15

  The influence on the resistance formation of polymers attached to antibiotics has rarely been investigated. In this study, ciprofloxacin (CIP) was conjugated to poly(2-methyl-2-oxazoline)s with an ethylene diamine end group (Me-PMOx28-EDA) via two different spacers (CIP modified with α,α′-dichloro-p-xylene—xCIP, CIP modified with chloroacetyl chloride—eCIP). The antibacterial activity of the conjugates against a number of bacterial strains shows a great dependence on the nature of the spacer. The Me-PMOx39-EDA-eCIP, containing a potentially cleavable linker, does not exhibit a molecular weight dependence on antibacterial activity in contrast to Me-PMOx27-EDA-xCIP. The resistance formation of both conjugates against Staphylococcus aureus and Escherichia coli was investigated. Both conjugates showed the potential to significantly delay the formation of resistant bacteria compared to the unmodified CIP. Closer inspection of a possible resistance mechanism by genome sequencing of the topoisomerase IV region of resistant S. aureus revealed that this bacterium mutates at the same position when building up resistance to CIP and to Me-PMOx27-EDA-xCIP. However, the S. aureus cells that became resistant against the polymer conjugate are fully susceptible to CIP. Thus, conjugation of CIP with PMOx seems to alter the resistance mechanism.

  与抗生素结合的聚合物对耐药性形成的影响很少被研究。在本研究中，环丙沙星（CIP）通过两种不同的间隔器与端基为乙烯二胺的聚（2-甲基-2-噁唑啉）(Me-PMOx28-EDA)结合（CIP修饰的α,α'-二氯对二甲苯—xCIP，CIP修饰的氯乙酰氯—eCIP）。结合物对多种细菌株的抗菌活性显示出对间隔器性质的高度依赖。包含潜在可裂解连接子的Me-PMOx39-EDA-eCIP与Me-PMOx27-EDA-xCIP相比，抗菌活性不表现出分子量的依赖性。对这两种结合物在金黄色葡萄球菌和大肠杆菌中的耐药性形成进行了研究。与未修饰的CIP相比，这两种结合物均表现出显著延迟耐药细菌形成的潜力。通过对耐药金黄色葡萄球菌的拓扑异构酶IV区域进行基因组测序，进一步检查了可能的耐药机制，发现该细菌在对CIP和Me-PMOx27-EDA-xCIP形成耐药时，需要在相同位置发生突变。然而，对聚合物结合物产生耐药性的金黄色葡萄球菌细胞对CIP仍然完全敏感。因此，将CIP与PMOx结合似乎改变了耐药机制。
• Piperazinyl-linked fluoroquinolone dimers possessing potent antibacterial activity against drug-resistant strains of Staphylococcus aureus
  作者：Robert J. Kerns、Michael J. Rybak、Glenn W. Kaatz、Flamur Vaka、Raymond Cha、Richard G. Grucz、Veena U. Diwadkar、Tracey D. Ward

  DOI：10.1016/s0960-894x(03)00208-7

  日期：2003.5

  The synthesis of symmetric and asymmetric piperazinyl-linked dimers of the fluoroquinolone class of antibiotics is described. Specific dimers are shown to possess potent antibacterial activity against drug-resistant strains of Staphylococcus aureus, including strains possessing resistance due to the NorA multidrug efflux pump and a mutation in the quinolone resistance-determining region of topoisomerase IV. (C) 2003 Elsevier Science Ltd. All rights reserved.
• Structural features of piperazinyl-linked ciprofloxacin dimers required for activity against drug-resistant strains of Staphylococcus aureus
  作者：Robert J Kerns、Michael J Rybak、Glenn W Kaatz、Flamur Vaka、Raymond Cha、Richard G Grucz、Veena U Diwadkar

  DOI：10.1016/s0960-894x(03)00376-7

  日期：2003.7

  We previously demonstrated that piperazinyl-linked fluoroquinolone dimers possess potent antibacterial activity against drug-resistant strains of Staphylococcus aureus. In this study, we report the preparation and evaluation of a series of incomplete dimers toward ascertaining structural features of piperazinyl-linked ciprofloxacin dimers that render these agents refractory to fluoroquinolone-resistance mechanisms in Staphylococcus aureus. (C) 2003 Elsevier Science Ltd. All rights reserved.