title: Synthesis, characterization and in vitro antimicrobial activity of novel sulfonylureas of 15-membered azalides.
abstract: Three series of the novel sulfonylurea derivatives of 15-membered azalides, i.e. 9a-N-[N'-(aryl)sulfonylcarbamoyl] (4a-4f, 5a-5f), 9a-N-{N'-[(aryl)sulfonylcarbamoyl-gamma-aminopropyl]} (10a-10f, 11a, 11c) and 9a-N-{N'-(beta-cyanoethyl)-N'-[(aryl)sulfonylcarabamoyl-gamma-aminopropyl]} (14a-14f, 15a, 15b, 15f) derivatives of 9-deoxo-9-dihydro-9a-aza-9a-homoerythromycin A (2) and 5-O-desosaminyl-9-deoxo-9-dihydro-9a-aza-9a-homoerythronolide A (3) were prepared and their structures elucidated by NMR and IR spectroscopic methods and mass spectrometry. Minimal inhibitory concentration (MIC) of these compounds was determined on a panel of sensitive and resistant Gram-positive and Gram-negative bacterial strains. Several compounds of the series of 9a-N-[N'-(aryl)sulfonylcarbamoyl] derivatives that showed significant improvements in activity against inducible resistant Streptococcus pyogenes strain were suggested for further optimization.
authors.affiliation: PLIVA-Research and Development Ltd., Prilaz baruna Filipovica 29, HR-10000 Zagreb, Croatia. Mirjana.Bukvic.Krajacic@pliva.hr
authors.forename: Mirjana Bukvić
authors.initials: MB
authors.lastname: Krajacić
authors.forename: Nedjeljko
authors.initials: N
authors.lastname: Kujundzić
authors.forename: Miljenko
authors.initials: M
authors.lastname: Dumić
authors.forename: Mario
authors.initials: M
authors.lastname: Cindrić
authors.forename: Karmen
authors.initials: K
authors.lastname: Brajsa
authors.forename: Biserka
authors.initials: B
authors.lastname: Metelko
authors.forename: Predrag
authors.initials: P
authors.lastname: Novak
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology*; D001372:Aza Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D024881:Drug Resistance, Bacterial; D007202:Indicators and Reagents; D009682:Magnetic Resonance Spectroscopy; D008826:Microbial Sensitivity Tests; D021241:Spectrometry, Mass, Electrospray Ionization; D013055:Spectrophotometry, Infrared; D013297:Streptococcus pyogenes / Q000187:drug effects; D013329:Structure-Activity Relationship; D013453:Sulfonylurea Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D000900:Anti-Bacterial Agents; D001372:Aza Compounds; D007202:Indicators and Reagents; D013453:Sulfonylurea Compounds