莫西沙星类似物的合成及其体内外抗菌活性  

Synthesis and antibacterial activity of moxifloxacin analogues in vitro and in vivo

作　　者：王菊仙[1] 曹珏[1] 李素杰[1] 刘明亮[1] 郭慧元[1] 

机构地区：[1]中国医学科学院中国协和医学院医药生物技术研究所,北京100050

出　　处：《中国抗生素杂志》2008年第11期674-677,共4页Chinese Journal of Antibiotics

摘　　要：目的合成具有良好抗菌活性的莫西沙星类似物。方法以盐酸莫西沙星为原料,先与甲基乙烯酮发生加成反应生成N-(3-氧代-1-正丁基)莫西沙星(1),接着经氧化并重排及中和反应得到N-羟基莫西沙星(2)。测定化合物1和2的体内外抗菌活性。结果1的体外活性与对照药莫西沙星基本相当,且优于2(P<0.05);1和2对试验菌株所致小鼠系统感染均具有疗效,其中1的体内疗效与对照药莫西沙星基本相当(P>0.05),且优于2(P<0.05)。结论在莫西沙星7-位侧链的亚氨基上引入3-氧代-1-正丁基后其活性基本保持,但引入羟基后其活性明显降低。Objective To synthesize moxifloxacin analogues which could have high in vivo antibacterial activity. Methods Treatment of moxifioxacin hydrochloride with methyl vinyl ketone provided N-（3- oxobutyl） moxifloxacin （1）, which was converted to N-hydroxy moxifloxacin （2） via oxidation （N-oxide）, spontaneously rearrangement and neutralization. Antibacterial activity of 1 and 2 was evaluated and compared with moxifloxacin. Result The in vitro antibacterial activity against 50 Gram-negative and 110 Gram-positive strains of 1 was comparable to moxifloxacin, but higher than 2 （P〈0. 05）. The in vivo results showed 1 had as good internal protection as moxifloxacin （P〉0.05） against systemic infection model in mice, and higher than 2 （P〈0.05）. Conclusion Introduction of 3-oxohutyl or hydroxyl into moxifloxacin resulted in comparable or decreasing antibacterial activities.

关 键 词：氟喹诺酮 莫西沙星 莫西沙星类似物 合成 体内 外抗菌活性 

分 类 号：R978.19[医药卫生—药品]