dl-7-(4,4-二甲基-3-氨甲基-吡咯烷-1-基)-喹诺酮类化合物的合成与抗菌作用

目的寻找新的高效抗革兰氏阳性菌的喹诺酮类药物。方法设计合成了dl-7-(4,4-二甲基-3-氨甲基-吡咯烷-1-基)-1-环丙基-6-氟-8-甲氧基-1,4-二氢-4-氧代喹啉-3-羧酸及其类似物，测定其体外活性。结果共合成10个目标化合物，经¹H NMR，MS确证其结构。目标化合物具有良好的抗革兰氏阳性菌的活性，尤其是化合物22不仅对4株革兰氏阳性耐药菌(两株MRSA，两株MRSE)的活性表现突出，MIC值为0.015～0.5 mg·L^-1，其活性是加替沙星(MIC值为0.125～16 mg·L^-1)的4～128倍，而且，对铜绿假单孢菌03-5的MIC值为0.008 mg·L^-1，其活性是加替沙星(MIC值为0.03 mg·L^-1)的4倍。结论化合物22值得进一步深入评价。

Synthesis and antibacterial activity of dl-7-(4,4-dimethyl-3-aminomethylpyrrolidinyl)-quinolones

AIM: To explore new agents of quinolone derivatives with high activity against Gram-positive organisms. METHODS: dl-7-(4,4-Dimethyl-3- aminomethylpyrrolidinyl)-quinolones were designed and synthesized, and their activity against Gram-positive organisms was tested in vitro. RESULTS: Ten target compounds were obtained. The structures of these compounds were confirmed by 1H NMR, MS. The target compounds with dl-4,4-dimethyl-3-( methyl) aminomethylpyrrolidine side chains had high activity against Gram-positive organisms. Especially the MIC values of compound 22 for 4 strains of Gram-positive resistant bacteria (two strains of MRSA and two of MRSE) were 0.015 -0.5 mg x L(-), which exhibited more potent activities than gatifloxacin (4 - 128 times). Its MIC value for Pseudomonas aeruginosa 03-5 (0.008 mg x L(-1)) was 4 times as that of gatifloxacin (0.03 mg x L(-1)). CONCLUSION: The compound 22 showed high activity against Gram-positive organisms in vitro and it is worth of more investigation.