Synthesis, Characterization and In Vitro Antimicrobial Activity of Novel Sulfonylureas of 15-Membered Azalides

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-γ-aminopropyl]} ( 10a ∼ 10f , 11a , 11c ) and 9a- N -{ N ′-(β-cyanoethyl)- N ′-[(aryl)sulfonylcarabamoyl-γ-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.