A novel series of parenteral cephalosporins exhibiting potent activities against both Pseudomonas aeruginosa and other Gram-negative pathogens. Part 2: Synthesis and structure–activity relationships Original Research Article

A novel series of 7β-[2-(2-amino-5-chloro-thiazol-4-yl)-2(Z)-((S)-1-carboxyethoxyimino)acetamido]cephalosporins bearing various pyridinium groups at the C-3′ position were synthesized and their in vitro antibacterial activities against Gram-negative pathogens including Pseudomonas aeruginosa and several Gram-positive pathogens were evaluated. Among the cephalosporins prepared, we found that a cephalosporin bearing the 2-amino-1-(3-methylamino-propyl)-1H-imidazo[4,5-b]pyridinium group at the C-3′ position (8a) showed potent and well-balanced antibacterial activities against P. aeruginosa and other Gram-negative pathogens including the strains which produce class C β-lactamase and extended spectrum β-lactamase (ESBL). Compound 8a also showed efficacious in vivo activity and high stability against AmpC β-lactamase. These findings indicate that 2-aminoimidazopyridinium having an aminoalkyl group at the 1-position as a C-3′ side chain is suitable for cephalosporins bearing an aminochlorothiazolyl moiety and a carboxyethoxyimino moiety on the C-7 side chain.