5-氨基-6,8-二氟-1-(5-氟-2-吡啶基)-7-(3-甲基-1-哌嗪基)-1,4-二氢-4-氧代喹啉-3-羧酸及其类似物的合成及其抗菌作用

SYNTHESIS AND ANTIBACTERIAL ACTIVITY OF 5-AMINO-6, 8-DIFLUORO-1-(5-FLUORO-2-PYRIDYL)-7-(3-METHYL-1-PIPERAZINYL)-1,4-DIHYDRO-4-OXO-3-QUINOLINECARBOXYLIC ACID AND ITS ANALOGUES

摘要: 目的设计合成1-位为5-氟-2-吡啶基的吡酮酸衍生物,并对其抗菌活性进行初步评价.方法以2,3,4,5-四氟-6-硝基苯甲酰基乙酸乙酯和2,4,5-三氟-3-甲氧基苯甲酰基乙酸乙酯为原料,经多步反应合成8个5-氨基-6,8-二氟-1-(5-氟-2-吡啶基)-7-(3-甲基-1-哌嗪基)-1,4-二氢-4-氧代喹啉-3-羧酸及其类似物.结果共合成15个新化合物,经¹HNMR和MS确证其结构,其中8个(8-15)为目标物.结论8个目标物对金黄色葡萄球菌-16、大肠埃希氏菌-26和铜绿假单孢菌-17的体外活性均低于环丙沙星.

Abstract: AIM To design and synthesize 1-(5-fluoro-2-pyridyl) quinolone derivatives, and to study their in vitro antibacterial activities. METHODS Eight new compounds of 5-amino-6,8-difluoro-1-(5-fluoro-2-pyridyl)-7-(3-methyl-1-piperazinyl)-1,4-dihydro-4-oxo-3-quinolinecarboxylic acid and its analogues were synthesized from ethyl 6-nitro-2,3,4,5-terafluorobenzoylacetate and ethyl 3-methoxy 2,4,5-trifluorobenzoylacetate through 5 or 6 steps. RESULTS Fifteen new compounds (1-15) were obtained including 8 desired compounds (8-15). The structures of the compounds were determined by ¹HNMR, MS. CONCLUSION In vitro antibacterial activities of the compounds (8-15) against Staphylococcus aureus-16, Escherichia coli-26 and Pseudomonas aeruginosa-17 were lower than control of ciprofloxacin.