S-3578, A New Broad Spectrum Parenteral Cephalosporin Exhibiting Potent Activity Against both Methicillin-resistant Staphylococcus aureus (MRSA) and Pseudomonas aeruginosa Synthesis and Structure-activity Relationships

Abstract

A series of 7-aminothiadiazolylcephalosporins having a 1-(substituted)-1H-imidazo[4, 5-b]pyridinium group at the C-3' position of the cephem nucleus were synthesized and evaluated for in vitro antibacterial activities. Among the cephalosporins prepared in this study, 7β-[2-(5-amino-1, 2, 4-thiadiazol-3-yl)-2(Z)-ethoxyiminoacetamido]-3-[1-(3-methylaminopropyl)-1H-imidazo[4, 5-b]pyridinium-4-yl]methyl-3-cephem-4-carboxylate sulfate (S-3578) showed extremely potent broad spectrum activity against both Gram-positive bacteria including methicillin-resistant Staphylococcus aureus (MRSA) and Gram-negative bacteria including Pseudomonas aeruginosa, and good water solubility.