Synthesis and antibacterial activity of novel 11-[3-[(arylcarbamoyl)oxy]propylamino]-11-deoxy-6-O-methyl-3-oxoerythromycin A 11-N, 12-O-cyclic carbamate derivatives

摘要

A series of novel 11-[3-[(arylcarbamoyl)oxy]propylamino]-11-deoxy-6-O-methyl-3-oxoerythromycin A 11-N, 12-O-cyclic carbamate derivatives (6a-h) were designed, synthesized and evaluated for their antibacterial activities in vitro. Most of these compounds had significant antibacterial activity against two groups of pathogens of Methicillin-sensitive Staphylococcus aureus (MIC50 = 0.031-2 mu g ml(-1)) except 6g and Methicillin-sensitive S. epidermidis (MIC50 = 0.031-0.5 mu g ml(-1)). MIC90 of 6d against Methicillin-resistant S. epidermidis was at least 16-fold better than that of erythromycin (EMA), azithromycin (AZM) and ABT-773. 6d and 6e had more potent antibacterial activity against S. pneumoniae than EMA, AZM and ABT-773. In particular, compounds 6d and 6e also showed relatively potent activity against Haemophilus influenzae and Streptococcus hemolyticus.