门冬氨酸优力沙星的合成和初步药理试验

Synthesis and Preliminary Pharmacological Test of Ulifloxacin Aspartate

6-氟-1-甲基-4-氧代-7-(1-哌嗪基)-1H,4H-[1,3]硫氮杂环丁烷并[3,2-a]喹啉-3-羧酸在水-丙酮中与L-门冬氨酸反应,加丙酮析出结晶,得新化合物门冬氨酸优力沙星,收率87.6%。大鼠尾静脉注射给药28d的毒性实验显示,10mg/kg剂量组有关指标未观察到有毒理学意义的改变。体外抑菌实验表明,本品对金黄色葡萄球菌、大肠埃希菌、铜绿假单胞菌等的MIC值分别为0.25～0.5μg/ml、<0.0313μg/ml和0.25～0.5μg/ml(以优力沙星计),显示出较好的抗菌效果。

Ulifloxacin aspartate was prepared from 6-fluoro-1-methyl-4-oxo-7-（1-piperazinyl）-1H,4H- [ 1,3 ] thiazeto [3,2-α] quinoline-3-carboxylic acid and L-aspartic acid in H2O-acetone with a yield of 87.6 %. The result of toxicity test showed that the no-observed-adverse-effect level of ulifloxacin aspartate was 10mg/kg for 4-week repeated dose in rats. MICs of ulifloxacin aspartate in vitro against Staphylococcus aureus, Escherichia coli. and Pseudomonas aeruginosa were 0.25-0.5μg/ml, 〈0.0313μg/ml and 0.25-0.5μg/ml, respectively （based on ulifloxacin）.