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Discovery of 4''-ether linked azithromycin-quinolone hybrid series: influence of the central linker on the
Dražen Pavlović1, Stjepan Mutak1
1PLIVA Research Institute, Prilaz baruna Filipovića 29, 10000 Zagreb, Croatia.
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.
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