新型氟喹诺酮类衍生物的设计合成及其体外抗菌活性的初探

The design,synthesis and in vitro antibacterial activities of novel fluoroquinolone derivatives

目的设计、合成系列新型氟喹诺酮类衍生物，并初筛其体外抗菌活性。方法通过酰胺键在洛美沙星、左氧氟沙星和加替沙星的C-7位引入乙酰基、正己酰基、苯乙酰基和三甲氧基苯乙酰基，制备了一系列氟喹诺酮类衍生物，并通过二倍稀释法进行抗菌活性初筛。结果与讨论共制备12个全新目标物，结构经^1HNMR、^13CNMR和HRMS确证。通过对金黄色葡萄球菌、大肠埃希菌和铜绿假单胞菌的体外抗菌活性初筛，发现化合物7的抗菌活性优于阳性对照。此外，在C-7位引入乙酰基的化合物7～9的抗菌活性显著优于母核相同、C-7侧链不同的结构类似物。

OBJECTIVE To design and synthesize a series of novel fluoroquinolone derivatives in order to investigate their in vitro antibacterial effects. METHODS A novel group of fluoroquinolones were synthesized by introducing ethyl, n - hexy[, phenethyl and trimethoxyphenemyl into the C - 7 position of Lomefloxacin, Levofloxacin and Gatifloxacin with an amide bond. Double - dilution method was used to measure the antibacterial activities. RESULTS and CONCLUSION 12 novel compounds were prepared and their struc- ture were confirmed by ^1 HMR, ^13 CNMR and HRMS. The compounds were evaluated for their antibacterial activities against S. aureus, E. coli and P. aeruginosa. Among them, the most potent was compound 7. In addition, it was found that compounds 7 - 9 with an acetyl group introduced into the C -7 position had significant advantages regarding antibacterial activity compared to compounds with the same quinolone moiety but different C -7 side chains.