7-(3-甲基-3-甲胺基-4-烷氧亚胺基-1-哌啶基)喹诺酮类化合物的合成与体外抗菌作用(英文)

Synthesis and in vitro antibacterial activity of 7-(4-alkoxyimino-3-methyl-3-methylaminopiperidin-1-yl)quinolones

为寻找新的喹诺酮类抗菌药,设计合成了16个7-(3-甲基-3-甲胺基-4-烷氧亚胺基-1-哌啶基)喹诺酮类化合物,并测定其体外抗菌活性。目标化合物结构经1HNMR和HRMS得到确证,并用单晶X-衍射分析确定其双键构型。化合物14k和14m～14o对所试验的5株革兰阳性菌和5株革兰阴性菌表现出良好的广谱抗菌活性(MIC:0.25～16μg·mL-1),其中活性最强的化合物14o对金葡菌、表葡菌、粪肠球菌和大肠埃希菌的活性(MIC:0.25～1μg·mL-1)与左氧氟沙星相当,对肺炎链球菌的活性(MIC:4μg·mL-1)是左氧氟沙星的8倍,但总体上弱于吉米沙星。

To explore new agents of quinolone derivatives with high antibacterial activity,7-（4-alkoxyimino-3-methyl-3-methylaminopiperidin-1-yl）quinolones were designed and synthesized,and their activity against gram-positive and gram-negative strains was tested in vitro.Sixteen target compounds were obtained.Their structures were established by 1H NMR,HRMS and X-ray crystallographic analysis.Compounds 14k and 14m-14o show good antibacterial activity against the tested five gram-positive strains and five gram-negative strains（MIC：0.25-16 μg·mL-1）,of which the most active compound 14o is 8-fold more potent than levofloxacin against S.pneumoniae（MIC：4 μg·mL-1）,and comparable to levofloxacin against S.aureus,S.epidermidis,E.faecalis and E.coli（MIC：0.25-1 μg·mL-1）,but generally less potent than gemifloxacin.