Synthesis and antibacterial activity of novel 3-O-carbamoyl derivatives of clarithromycin and 11,12-cyclic carbonate azithromycin.
Two series of novel 3-O-carbamoyl derivatives of clarithromycin and 11,12-cyclic carbonate azithromycin were designed, synthesized and evaluated for their in vitro antibacterial activities. Compounds 4j and 4k were the most potent activity against erythromycin-susceptible Staphylococcus aureus, Streptococcus pyogenes and Streptococcus pneumoniae, which were comparable to those of clarithromycin and azithromycin. Compounds 4d, 4h and 4i showed potent activity against erythromycin-resistant S. pneumoniae encoded by the mef gene and compounds 4h and 4i displayed greatly improved activity against erythromycin-resistant S. pneumoniae encoded by the erm gene. Compound 7c exhibited improved activity against erythromycin-resistant S. pneumoniae encoded by the erm and mef genes.
Zhang
Ling
L
Department of Medicinal Chemistry, School of Pharmaceutical Sciences, Shandong University, 44 West Culture Road, Jinan 250012, PR China.
Song
Linchen
L
Liu
Zhaopeng
Z
Li
Hui
H
Lu
Yingdong
Y
Li
Zerong
Z
Ma
Shutao
S
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000494:pharmacology; D017963:Azithromycin / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*; D017291:Clarithromycin / Q000031:analogs & derivatives / Q000138:chemical synthesis* / Q000494:pharmacology*; D004353:Drug Evaluation, Preclinical; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D013296:Streptococcus pneumoniae / Q000145:classification / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D017963:Azithromycin; D017291:Clarithromycin