7-[3-氨甲基-4-(脲亚氨基)吡咯烷-1-基]喹诺酮衍生物的合成与抗菌作用研究(英文)  

Synthesis and in vitro antibacterial activity of 7-[3-(aminomethyl)-4-(semicarbazono)pyrrolidin-1-yl]quinolone derivatives

作　　者：郭强[1] 冯连顺[1] 刘明亮[1] 郭慧元[1] 李素杰[1] 

机构地区：[1]中国医学科学院北京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》2011年第6期434-440,共7页Chinese Journal of Antibiotics

基　　金："重大新药创制"科技重大专项(2009ZX09301-003);中央级公益性科研院所基本科研业务专项IMBF200912

摘　　要：目的寻找新的喹诺酮类抗菌药。方法设计合成7-位具有较强亲水性取代基的7个氟喹诺酮衍生物，测定其体外抗菌活性。结果化合物10对金葡菌（包括MRSA）和表葡菌（包括MRSE）的活性（MIC：0．06-4μg/mL）与左氧氟沙星和吉米沙星基本相当。化合物11对肺炎链球菌08-2的活性（MIC：0．25μg／mL）分别是左氧氟沙星和吉米沙星的128倍和32倍，化合物12对肺炎克雷伯菌09—22和09—23的活性（MIC：1μg／mL）分别是左氧氟沙星和吉米沙星的16倍和4倍，但目标物对革兰阴性菌的活性普遍弱于对照药。结论7-位取代基的水溶性并非决定喹诺酮抗菌活性的主要因素。Objective To find new antibacterial agents of quinolones with high activity. Methods Seven fluoroquinolone derivatives with more water solubility substituent at C-7 position were designed, synthesized and evaluated for their in vitro activity against seventeen Gram-positive and thirteen Gram-negative strains. Results The activity of compound 10（MIC： 0.06-4μg/mL） was comparable to levofloxacin and gemifloxacin against S. aureus including MRSA and S. epidermidis including MRSE. Compound I（MIC： 0.25μg/mL） is 32-128 fold more potent than both the reference drugs against S. pneumoniae 08-2, and compound 12（MIC： 1μg/mL） is 16 and 4 fold more potent than levofloxacin and gemifloxacin against both K. pneumoniae 09-22 and 09-23, respectively. Conclusion The water solubility of the substituent at C-7 position is not main parameter affecting antibacterial activity.

关 键 词：氟喹诺酮 合成 体外抗菌活性 

分 类 号：R914.5[医药卫生—药物化学]