1. Discovery of 4′′-Ether Linked Azithromycin-Quinolone Hybrid Series: Influence of the Central Linker on the Antibacterial Activity
- Author
-
Dražen Pavlović and Stjepan Mutak
- Subjects
Fastidious organism ,medicine.drug_class ,business.industry ,Organic Chemistry ,Telithromycin ,Azithromycin ,medicine.disease_cause ,Quinolone ,Antimicrobial ,Biochemistry ,Cethromycin ,Microbiology ,Haemophilus influenzae ,Drug Discovery ,Streptococcus pyogenes ,medicine ,business ,medicine.drug - Abstract
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 7f 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.
- Published
- 2011