1-Cyclopropyl-7-(3-ethylamino-azetidin-1-yl)-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid | 132770-51-5

• 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: 1-Cyclopropyl-7-(3-ethylamino-azetidin-1-yl)-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid
• 英文别名: 1-Cyclopropyl-7-[3-(ethylamino)azetidin-1-yl]-6-fluoro-4-oxoquinoline-3-carboxylic acid
• CAS: 132770-51-5
• 化学式: C₁₈H₂₀FN₃O₃
• 分子量: 345.374
• InChiKey: CZKWJYBHLZFPAO-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  -0.6
• 重原子数：
  25
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.44
• 拓扑面积：
  72.9
• 氢给体数：
  2
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  1-Cyclopropyl-7-(3-ethylamino-azetidin-1-yl)-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid 、 碘甲烷 以 乙醇 、 氯仿 为溶剂， 反应 24.0h， 以58%的产率得到[1-(3-Carboxy-1-cyclopropyl-6-fluoro-4-oxo-1,4-dihydro-quinolin-7-yl)-azetidin-3-yl]-ethyl-dimethyl-ammonium; iodide
  参考文献：
  名称：

  7-氮杂环丁烷基喹诺酮类作为抗菌剂。2. 7-（2,3-二取代-1-氮杂环丁烷基）-4-氧代喹啉-和-1,8-萘啶-3-羧酸的合成及生物活性。喹诺酮与氮杂环丁烷部分的性质和构效关系。

  摘要：

  一系列7-（2,3-二取代-1-氮杂环丁烷基）-1,4-二氢-6-氟-4-氧代喹啉-和-1,8-萘啶-3-羧酸，在1处具有不同的取代基制备5-，5-和8-位，以研究对氮杂环丁烷部分2位上的取代基的效能和理化性质的影响。在体外确定针对革兰氏阳性和革兰氏阴性细菌的标题化合物的活性，并使用小鼠感染模型确定所选衍生物的体内功效。发现6b，6c和6d的X射线晶体结构与相应的AM1计算的几何结构合理吻合。建立了所有合成的7-氮杂环丁烷基喹诺酮类和萘啶类的抗菌能力与计算出的电子性质和实验容量因子之间的相关性。将所选衍生物的抗菌功效，药代动力学和理化性质与相关的7-（3-氨基-1-氮杂环丁烷基）和7-（3-氨基-3-甲基-1-氮杂环丁烷基）类似物进行了比较（第1部分，请参见： J. Med。Chem。1993，36，801-810）。N-1处的环丙基或取代的苯基与C-7处的反-3-氨基-2-甲基-1-氮杂

  DOI：

  10.1021/jm00050a016
• 作为产物：
  描述：

  1-环丙基-6,7-二氟-1,4-二氢-4-氧喹啉-3-羧酸 在 吡啶 、 sodium hydroxide 、 三乙胺 作用下， 反应 5.0h， 生成 1-Cyclopropyl-7-(3-ethylamino-azetidin-1-yl)-6-fluoro-4-oxo-1,4-dihydro-quinoline-3-carboxylic acid
  参考文献：
  名称：

  7-Azetidinylquinolones as antibacterial agents. Synthesis and structure-activity relationships

  摘要：

  A series of novel antibacterial quinolones and naphthyridones has been prepared which contain 7-azetidinyl substituents in place of the usual piperazine or aminopyrrolidine groups. These azetidinyl derivatives were evaluated for in vitro activity by determining minimum inhibitory concentrations against a variety of bacteria. In vivo efficacy in the mouse infection model and blood levels in the mouse were determined for several compounds. The influence on the structure-activity relationships of varying substituents in the azetidine ring and at position 8 (CH, CF, CCl, N) and N-1 (ethyl, fluoroethyl, cyclopropyl, tert-butyl, 4-fluorophenyl, and 2,4-difluorophenyl) was also studied. Compounds with outstandingly broad-spectrum activity, particularly against Gram-positive organisms, improved in vivo efficacy, and high blood levels were identified in this work. 7-Azetidinyl-8-chloroquinolones were considered as warranting further development.

  DOI：

  10.1021/jm00059a002

文献信息

• 7-Azetidinylquinolones as Antibacterial Agents. 2. Synthesis and Biological Activity of 7-(2,3-Disubstituted-1-azetidinyl)-4-oxoquinoline- and -1,8-naphthyridine-3-carboxylic Acids. Properties and Structure-Activity Relationships of Quinolones with an Azetidine Moiety
  作者：Jordi Frigola、Antoni Torrens、Jose A. Castrillo、Josep Mas、David Vano、Juana M. Berrocal、Carme Calvet、Leonardo Salgado、Jordi Redondo

  DOI：10.1021/jm00050a016

  日期：1994.11

  3-disubstituted-1-azetidinyl)-1,4-dihydro-6-fluoro-4- oxoquinoline- and -1,8-naphthyridine-3-carboxylic acids, with varied substituents at the 1-, 5-, and 8-positions, was prepared to study the effects on potency and physicochemical properties of the substituent at position 2 of the azetidine moiety. The activity of the title compounds was determined in vitro against Gram-positive and Gram-negative bacteria

  一系列7-（2,3-二取代-1-氮杂环丁烷基）-1,4-二氢-6-氟-4-氧代喹啉-和-1,8-萘啶-3-羧酸，在1处具有不同的取代基制备5-，5-和8-位，以研究对氮杂环丁烷部分2位上的取代基的效能和理化性质的影响。在体外确定针对革兰氏阳性和革兰氏阴性细菌的标题化合物的活性，并使用小鼠感染模型确定所选衍生物的体内功效。发现6b，6c和6d的X射线晶体结构与相应的AM1计算的几何结构合理吻合。建立了所有合成的7-氮杂环丁烷基喹诺酮类和萘啶类的抗菌能力与计算出的电子性质和实验容量因子之间的相关性。将所选衍生物的抗菌功效，药代动力学和理化性质与相关的7-（3-氨基-1-氮杂环丁烷基）和7-（3-氨基-3-甲基-1-氮杂环丁烷基）类似物进行了比较（第1部分，请参见： J. Med。Chem。1993，36，801-810）。N-1处的环丙基或取代的苯基与C-7处的反-3-氨基-2-甲基-1-氮杂
• 7-Azetidinylquinolones as antibacterial agents. Synthesis and structure-activity relationships
  作者：Jordi Frigola、Juan Pares、Jordi Corbera、David Vano、Ramon Merce、Antoni Torrens、Josep Mas、Eduard Valenti

  DOI：10.1021/jm00059a002

  日期：1993.4

  A series of novel antibacterial quinolones and naphthyridones has been prepared which contain 7-azetidinyl substituents in place of the usual piperazine or aminopyrrolidine groups. These azetidinyl derivatives were evaluated for in vitro activity by determining minimum inhibitory concentrations against a variety of bacteria. In vivo efficacy in the mouse infection model and blood levels in the mouse were determined for several compounds. The influence on the structure-activity relationships of varying substituents in the azetidine ring and at position 8 (CH, CF, CCl, N) and N-1 (ethyl, fluoroethyl, cyclopropyl, tert-butyl, 4-fluorophenyl, and 2,4-difluorophenyl) was also studied. Compounds with outstandingly broad-spectrum activity, particularly against Gram-positive organisms, improved in vivo efficacy, and high blood levels were identified in this work. 7-Azetidinyl-8-chloroquinolones were considered as warranting further development.