N-thiolated β-lactam antibacterials:: Defining the role of unsaturation in the C4 side chain

N-Methylthio beta-lactams represent a novel family of antibacterial agents for methicillin-resistant Staphylococcus aureus (MRSA). The structure-activity functions and mechanism of action of these compounds, although still largely undefined, differ dramatically from those of all previously reported beta-lactam antibiotics. Prior work has established that the N-alkylthio moiety is required for antibacterial activity, and that a variety of unsaturated groups can be tolerated at C-4 of the lactam ring. This report describes the effect that unsaturation within the C-4 substituent has on antibacterial activity of these interesting new N-thiolated beta-lactams. (C) 2002 Elsevier Science Ltd. All rights reserved.