7-取代-1-取代-6,8-二氟-1,4-二氢-4-氧-3-喹啉羧酸化合物的合成及其抗菌活性

Synthesis of 7-substituted-1-substituted-6,8-difluoro-1,4-dihydro-4-oxo-3-quinolonecarboxylic acid compounds and their antibacterial activity in vitro

目的 :研究 7-取代 -1-取代 -6 ,8-二氟 -1,4-二氢 -4 -氧 -3-喹啉羧酸的合成、体外抗菌活性及其构效关系。方法 :通过缩合、Gould-Jacobs环合、亲核取代得到关键中间体 ,然后通过反应制得目标化合物。选用临床常见致病菌的标准菌株进行体外抗菌活性测定。结果 :设计合成 2 6个化合物 ,其中 2 0个化合物为首次报道。抗菌活性实验以氟罗沙星为对照 , i、 j和苯环上无取代的化合物 b1 、 b2 的活性比氟罗沙星稍好 ,特别是化合物 b2 的活性优于氟罗沙星。 结论 :合成的 2 6个化合物中有一些化合物显示了较好的抗菌活性 ,其中化合物 b2 的活性优于氟罗沙星。该类化合物值得进一步研究。

Objective: To study the synthesis, antibacterial activities and structure activity relationship of 7 substituted 1 substituted 6,8 difluoro 1,4 dihydro 4 oxo 3 quinolonecarboxylic acid compounds. Methods: The title compounds were synthesized through the process of condensation, Gould Jacobs cyclization, nucleophilic substitution. Antibacterial activities in vitro were determined with 10 kinds of common pathogenic bacteria. Results: Twenty six compounds of 7 substituted 1 substituted 6,8 difluoro 1,4 dihydro 4 oxo 3 quinolonecarboxylic acids were designed and synthesized. Among them 20 compounds were firstly reported. The chemical structures of all the compounds were determined by IR, 1HNMR and elementary analysis. Especially for type Ⅲ, compound Ⅲ b2 had more potent activity compared with fleroxacin in vitro . Conclusion: Among the 26 kinds of compounds synthesized, some of them have good antibacterial activities, the antibacterial activity of compound Ⅲ b2 is better than fleroracin. The compounds of type Ⅲ should be further studied.