N-甲酰基诺氟沙星 | 70459-04-0

• 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
• 中文名称: N-甲酰基诺氟沙星
• 中文别名: 诺氟沙星杂质G(EP)标准品；诺氟沙星EP杂质G
• 英文名称: 1-ethyl-6-fluoro-7-(4-formylpiperazin-1-yl)-1,4-dihydro-4-oxoquinoline-3-carboxylic acid
• 英文别名: 1-ethyl-6-fluoro-7-(4-formylpiperazin-1-yl)-4-oxo-1,4-dihydroquinoline-3-carboxylic acid；1-ethyl-6-fluoro-7-(4-formylpiperazinyl)-4-oxo-1,4-dihydro-3-quinolinecarboxylic acid；1-ethyl-6-fluoro-7-(4-formyl-piperazin-1-yl)-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid；1-ethyl-6-fluoro-7-(4-formyl)-piperazinyl-1,4-dihydro-4-oxo-quinoline-3-carboxylic acid；N-Formylnorfloxacin；1-ethyl-6-fluoro-7-(4-formylpiperazin-1-yl)-4-oxoquinoline-3-carboxylic acid
• CAS: 70459-04-0
• 化学式: C₁₇H₁₈FN₃O₄
• 分子量: 347.346
• InChiKey: BFGDJPQDLMOZQQ-UHFFFAOYSA-N

物化性质

• 熔点：
  292-293 °C(Solv: methanol (67-56-1))
• 沸点：
  622.1±55.0 °C(Predicted)
• 密度：
  1.453±0.06 g/cm3(Predicted)
• 溶解度：
  DMSO（轻微）、甲醇（轻微、加热、超声处理）

计算性质

• 辛醇/水分配系数(LogP)：
  1.2
• 重原子数：
  25
• 可旋转键数：
  3
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.35
• 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-甲酰基诺氟沙星 在 sodium hydroxide 作用下， 以 水 为溶剂， 生成 诺氟沙星
  参考文献：
  名称：

  Process for the preparation of quinoline-carboxylic acid derivatives

  摘要：

  本发明涉及一种制备喹啉羧酸衍生物的新的简单过程，其化学结构式为(I) ##STR1## 以及其水合物和治疗上可接受的盐。在公式中，取代基的含义如下：R是氢原子或甲酰基，R.sup.1是氢原子或直链或支链烷基，其具有1至4个碳原子，可以被羟基、卤素原子或氨基取代；或者是CH.sub.3 --NH基团，R.sup.2是氢原子或具有1至4个碳原子的烷基。根据本发明，通式(II) ##STR2## 或其酸加成盐与哌嗪在二甲基甲酰胺中反应，如果需要，所得到的通式(III) ##STR3## 可以经过酸性或碱性处理，或者优选地与肼或更优选地与肼水合物反应。

  公开号：

  US04935512A1
• 作为产物：
  描述：

  二乙基[[(3-氯-4-氟苯基)氨基]亚甲基]丙二酸酯 在 sodium hydroxide 、 potassium carbonate 、 三乙胺 作用下， 以 二苯醚 、 N,N-二甲基甲酰胺 为溶剂， 反应 18.0h， 生成 N-甲酰基诺氟沙星
  参考文献：
  名称：

  抗菌的6,7-和7,8-二取代的1-烷基-1,4-二氢-4-氧代喹啉-3-羧酸的结构活性关系。

  摘要：

  先前在抗菌单取代的1-乙基-1,4-二氢-4-氧代喹啉3-羧酸中进行的定量和定性结构活性研究促使我们合成了6,7,8-多取代的化合物。在本文中，描述了6,7-和7,8-二取代化合物及其衍生物的制备和抗菌活性。在这些化合物中，1-乙基-6-氟-1,4-二氢-4-氧代-7-（1-哌嗪基）喹啉-3-羧酸（34）具有许多显着的活性，并且比草酸（ 84）对抗革兰氏阳性和革兰氏阴性细菌。讨论了构效关系。

  DOI：

  10.1021/jm00186a014

文献信息

• Improved method for the synthesis of norfloxacin
  作者：G. A. Mokrushina、S. K. Kotovskaya、Z. M. Baskakova、G. M. Petrova、T. V. Kolmakova、V. N. Charushin、V. L. Rusinov、O. N. Chupakhin

  DOI：10.1007/bf02334643

  日期：1996.8

  by hydrolysis of the ester to acid. The reaction can be performed in boiling pyridine, picoline, pyridine toluene mixture, or triethylamine [5]. However, the above approaches to the synthesis of norfloxacin cannot be considered as perfect from the standpoint of chemistry because the relatively low mobility of the chlorine atom in position 7 of acid II or its ester III allows a competitive process of

  近年来，以氟喹诺酮类药物为通用名，出现了一批重要的临床抗菌药物，本质上是1,4-二氢-4-氧代-3-喹啉羧酸的氟衍生物。1983 年进入医药市场的第一种氟喹诺酮类药物是诺氟沙星，即 l-乙基-6-氟-7(哌嗪基)-4-氧代1,4-二氢-3-喹啉羧酸 (I) [1]。尽管与其他现代氟喹诺酮类药物相比，诺氟沙星对厌氧微生物的活性较低，但在治疗急性和慢性泌尿道感染方面非常有效，因此仍然是氟喹诺酮类药物中最畅销的制剂之一。此外，只有诺氟沙星被证明可用于婴儿治疗，没有负面副作用的风险。在文献描述的大部分合成途径中，诺氟沙星是通过在作用下置换l-乙基-6-氟-7-氯-4-氧代1,4-二氢-3-喹啉甲酸(II)中的氯原子而得到的无水哌嗪 [I 5 ] 或六水哌嗪 [5]。使用N-乙氧基羰基哌嗪代替哌嗪，然后将所得的I-乙基-6-氟-7-(4-乙氧基羰基哌嗪-基)4-氧代-1,4-二氢-3皂化，可以提高诺氟沙星的质量-喹啉羧酸与碱
• Discovery of membrane active benzimidazole quinolones-based topoisomerase inhibitors as potential DNA-binding antimicrobial agents
  作者：Ling Zhang、Dinesh Addla、Jeyakkumar Ponmani、Ao Wang、Dan Xie、Ya-Nan Wang、Shao-Lin Zhang、Rong-Xia Geng、Gui-Xin Cai、Shuo Li、Cheng-He Zhou

  DOI：10.1016/j.ejmech.2016.01.052

  日期：2016.3

  A series of novel benzimidazole quinolones as potential antimicrobial agents were designed and synthesized. Most of the prepared compounds exhibited good or even stronger antimicrobial activities in comparison with reference drugs. The most potent compound 15m was membrane active and did not trigger the development of resistance in bacteria. It not only inhibited the formation of biofilms but also disrupted the established Staphylococcus aureus and Escherichia coli biofilms. It was able to inhibit the relaxation activity of E. coli topoisomerase IV at 10 mu M concentration. Moreover, this compound also showed low toxicity against mammalian cells. Molecular modeling and experimental investigation of compound 15m with DNA suggested that this compound could effectively bind with DNA to form a steady 15m-DNA complex which might further block DNA replication to exert the powerful bioactivities. (C) 2016 Elsevier Masson SAS. All rights reserved.
• Discovery of the Highly Potent Fluoroquinolone-Based Benzothiazolyl-4-thiazolidinone Hybrids as Antibacterials
  作者：Rahul V. Patel、Se Won Park

  DOI：10.1111/cbdd.12299

  日期：2014.7

  A new series of fluoroquinolone‐based benzothiazolyl‐4‐thiazolidinone hybrids has been yielded via sulfated tungstate‐promoted highly accelerated N‐formylation at a piperazine residue of ciprofloxacin and norfloxacin entities. The formylated fluoroquinolone moieties were then coupled with substituted 2‐aminobenzothiazoles, which were generated from their respective para‐substituted amines to form corresponding Schiff base intermediates. The Schiff bases were then treated with thioglycolic acid to equip a new class of 4‐thiazolidinones to be analyzed for their antibacterial effects against two Gram‐positive (Staphylococcus aureus and Bacillus subtilis) and two Gram‐negative (Escherichia coli and Pseudomonas aeruginosa) bacterial strains and were found highly potent with lowest Minimum inhibitory concentrations (MIC), 1–2 μg/mL, that is, more potent than control drugs ciprofloxacin (3.12–6.25 μg/mL). Initial outcomes provided for these novel molecular systems will aid researchers to design and develop new antibacterial drugs. The structural assignments of the new products were done on the basis of FT‐IR, 1H NMR and 13C NMR spectroscopy, and elemental analysis.
• Design, synthesis, antibacterial activity and physicochemical parameters of novel N-4-piperazinyl derivatives of norfloxacin
  作者：Gamal El-Din A.A. Abuo-Rahma、Hatem. A. Sarhan、Gamal F.M. Gad

  DOI：10.1016/j.bmc.2009.04.027

  日期：2009.6

  We report herein the synthesis of some N-Mannich bases in addition to different N-4 substituents of norfloxacin. The antibacterial activities of the newly synthesized compounds were evaluated and correlated with their physicochemical properties. Results revealed that some of the tested compounds exhibited better inhibitory activities than the reference antibiotic norfloxacin against Pseudomonas aeruginosa, Escherichia coli, Klebsiella pneumonia and Staphylococcus aureus strains. Correlation results showed that there is no single physicochemical parameter that can determine the effect of N-4 piperazinyl group on the activity of these fluoroquinolones, where lipophilicity, molecular mass and electronic factors may influence the activity. (C) 2009 Elsevier Ltd. All rights reserved.
• Studies on prodrugs. 10. Possible mechanism of N-dealkylation of N-masked norfloxacins having several active methylene groups
  作者：Hirosato Kondo、Fumio Sakamoto、Yoshimasa Inoue、Goro Tsukamoto

  DOI：10.1021/jm00123a031

  日期：1989.3

  As a prodrug approach to norfloxacin (NFLX, 2), we have prepared several N-masked NFLXs (1a-f) and studied the cleavage mechanism of the C-N bond of N-masked NFLXs utilizing the following experiments: (1) the oxidation of N-masked NFLXs (1a-f) with m-chloroperbenzoic acid (MCPBA) and their subsequent cleavage to 2 in chloroform at room temperature or at 50 degrees C; (2) the liberation of NFLX from N-masked NFLXs after oral administration in mice. It was found that the chemical oxidative dealkylation of N-masked NFLXs proceeded when anion-stabilizing groups (e.g., CN, COR, COOR) are present on the alpha carbon of the nitrogen atom. In in vivo experiments, N-masked NFLXs having acidic hydrogens on the alpha carbon to the nitrogen atom also liberated NFLX (2) after oral administration.