Synthesis, characterization and in vitro antimicrobial activity of novel sulfonylureas of 15-membered azalides

• Published in: Journal of antibiotics Vol. 58; no. 6; pp. 380 - 389
• Main Authors: Krajacić, Mirjana Bukvić, Kujundzić, Nedjeljko, Dumić, Miljenko, Cindrić, Mario, Brajsa, Karmen, Metelko, Biserka, Novak, Predrag
• Format: Journal Article
• Language: English
• Published: Japan Nature Publishing Group 01-06-2005
• Subjects: Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - pharmacology; Aza Compounds - chemical synthesis; Aza Compounds - pharmacology; Bacteria - drug effects; Drug Resistance, Bacterial; Indicators and Reagents; Magnetic Resonance Spectroscopy; Mass spectrometry; Microbial Sensitivity Tests; Spectrometry, Mass, Electrospray Ionization; Spectrophotometry, Infrared; Streptococcus pyogenes; Streptococcus pyogenes - drug effects; Structure-Activity Relationship; Sulfonylurea Compounds - chemical synthesis; Sulfonylurea Compounds - pharmacology
• ISSN: 0021-8820; 1881-1469
• DOI: 10.1038/ja.2005.48

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.