Synthesis and antibacterial activity of 7-(3-amino-4-alkoxyimino-1 -piperidyl) -quinolones.
- Author:
Xiu-Yun WANG
1
;
Qiang GUO
;
Yu-Cheng WANG
;
Bing-Quan LIU
;
Ming-Liang LIU
;
Lan-Ying SUN
;
Hui-Yuan GUO
Author Information
1. Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, China.
- Publication Type:Journal Article
- MeSH:
Animals;
Anti-Bacterial Agents;
chemical synthesis;
pharmacology;
therapeutic use;
Female;
Gram-Negative Bacteria;
drug effects;
Gram-Positive Bacteria;
drug effects;
Male;
Methicillin-Resistant Staphylococcus aureus;
drug effects;
Mice;
Microbial Sensitivity Tests;
Molecular Structure;
Pneumococcal Infections;
drug therapy;
Quinolones;
chemical synthesis;
pharmacology;
therapeutic use;
Random Allocation;
Staphylococcal Infections;
drug therapy
- From:
Acta Pharmaceutica Sinica
2008;43(8):819-827
- CountryChina
- Language:Chinese
-
Abstract:
To explore new agents of quinolone derivatives with high activity against Gram-positive and Gram-negative microorganisms, 7-(3-amino-4-alkoxyimino-1-piperidyl) quinolones were designed and synthesized, and their activity against Gram-positive and Gram- negative microorganisms were tested in vivo and in vitro. Twenty one target compounds were obtained. Their structures were established by 1H NMR, HRMS and X-ray crystallographic analysis. The target compounds possess different antimicrobial activities against both Gram-negative and Gram-positive microorganisms. Compounds 14a and 14m have broad spectral antibacterial activities. They show better antibacterial activities against 12 strains Gram-positive bacteria than three references. In particular, their activities against S. aureus and S. epidermidis (including MRSA and MRSE) were 4 - 16 times than that of gemifloxacin and balofloxacin, and 8 - 64 times than that of levofloxacin. The MIC values to S. aureus strains of compounds 14a and 14m were 0.25 - 1 mg x L(-1) and 0.125 - 1 mg x L(-1), to S. epidermidis strains were 0.5 - 4 mg x L(-1) and 1 - 8 mg x L(-1) respectively. The in vivo results showed that they have as good internal protection as gemifloxacin and moxifloxacin against systemic infection model in mice (P > 0.05).
