N-芳酰烷基环丙沙星的合成及其抗菌活性

Synthesis and antibacterial activity of N-(aroylalkyl) ciprofloxacin

通过在环丙沙星7位的哌嗪环上引入脂溶性基团,以寻求抗菌谱更广、疗效更强、毒副作用更小的抗菌药物。根据前药设计原理,设计合成目标化合物,并研究其生物活性。获得了10种新化合物。新化合物的结构经1H NMR,13C NMR,MS和元素分析确证。目标化合物比环丙沙星具有更好的脂溶性;体外抗菌活性研究表明,大部分目标化合物对大肠埃希氏菌和铜绿假单孢菌具有较强的抑菌活性,其中化合物3d对大肠埃希氏菌抑菌活性高于环丙沙星。

In order to obtain the drugs with broader antibacterial spectrum,better antibacterial effect and less side-effect,modifications with lipid solublity group at the position of piperazinyl of ciprofloxacin were done.According to the prodrug design principle,a series of analogues were prepared and their biological activities were tested.The structures of the ten new compounds were confirmed by(~1H NMR),(^(13)C NMR),ESI-MS and elemental analysis.The lipid solublility of the new compounds was better than that of ciprofloxacin.The results of antibacterial activity in vitro showed that most of the target compounds possessed relatively high inhibiting activity on Escherichia coli and Pseudomonas aeruginosa.The antibacterial activity of the target compound 3d was higher than that of ciprofloxacin against Escherichia coli.