Discovery of 4 ''-Ether Linked Azithromycin-Quinolone Hybrid Series: Influence of the Central Linker on the Antibacterial Activity

作者：Pavlovic Drazen^*; Mutak Stjepan

来源：ACS Medicinal Chemistry Letters, 2011, 2(5): 331-336.

DOI：10.1021/ml100253p

• Macrolide antibiotics
• C-4 ''-substituted azithromycins
• quinolones
• macrolide resistance

A series of novel C-4"-substituted azithromycins was synthesized and evaluated for in vitro antibacterial activity against a panel of representative erythromycin-susceptible and macrolide-lincosamide-streptogramin (MLS) resistant pathogens. In summary, azithromycin and quinolone substructures merged in a mutually SAR-compatible design gave rise to a new class of antimicrobials with an improved spectrum and potency over azithromycin. Prototypical analogues 71 and, 8f display an improved potency versus azithromycin against Gram-positive and fastidious Gram-negative pathogens. In particular, these new leads maintain activity against MLS-resistant strains of Streptococcus pneumoniae and Streptococcus pyogenes. In addition, they represent an improvement over telithromycin (1) and cethromycin (2) against the fastidious Gram-negative pathogen Haemophilus influenzae.

• 出版日期2011-5