Original Article

Synthesis, Characterization and in vitro Antimicrobial Activity of Novel Sulfonylureas of 15-Membered Azalides

Mirjana BukviO_Bold_long.gif" KrajaO_Bold_long.gif"iO_Bold_long.gif", Nedjeljko KujundO_Bold_long.gif"iO_Bold_long.gif", Miljenko DumiO_Bold_long.gif", Mario CindriO_Bold_long.gif", Karmen BrajO_Bold_long.gif"a, Biserka Metelko, Predrag Novak

Received: February 25, 2005 / Accepted: June 3, 2005
© Japan Antibiotics Research Association

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-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.

Keywords Keywords azalides, sulfonylurea, synthesis, NMR and MS, antimicrobial activity

M. B. KrajaO_Bold_long.gif"iO_Bold_long.gif" (Corresponding authors), M. DumiO_Bold_long.gif", M. CindriO_Bold_long.gif": PLIVA-Research and Development Ltd., Prilaz
baruna Filipovica 29, HR-10000 Zagreb, Croatia, E-mail: Mirjana.Bukvic.Krajacic@pliva.hr
N. KujundO_Bold_long.gif"iO_Bold_long.gif", K. BrajO_Bold_long.gif"a, B. Metelko, P. Novak: PLIVA-Research Institute Ltd., Prilaz baruna Filipovica 29, HR-10000 Zagreb, Croatia