Studies on Anti-MRSA parenteral cephalosporins I. Synthesis and antibacterial activity of 7

Article abstract of DOI:10.7164/antibiotics.53.1053

In order to improve the antibacterial activity of cefozopran (CZOP) against methicillin-resistant Staphylococcus aureus (MRSA), we initiated chemical modification to introduce a 2-(5-amino-1,2,4-thiadiazol-3-yl)-2(Z)-hydroxyimino acetyl group at the C-7 position and a 3- or 6-substituted imidazo[1,2-b]pyridazinium or 5-substituted imidazo[1,2-a]pyridinium group at the C-3' position. Although this approach successfully enhanced the anti-MRSA activity of CZOP two to eight times, a slight decrease in the activity against Gram-negative bacteria including Pseudomonas aeruginosa was involved. Among the novel derivatives, 3-(6-aminoimidazo [1,2-b]pyridazinium-1-yl) methyl-7β-[2-(5-amino -1,2,4-thiadiazol-3-yl) -2(Z)-hydroxyiminoacetamidol]-3-cephem-4-carboxylate (44a) showed an excellent balance of activity against MRSA and Gram-negative bacteria.