Synthesis and structure-activity relationships of cephalosporins, 2-isocephems, and 2-oxaisocephems with C-3′ or C-7 catechol or related aromatics Original Research Article

A series of cephalosporins, 2-isocephems, and 2-oxaisocephems with C-3′ catechol-containing (pyridinium-4-thio)methyl groups and 2-isocephems with C-7 catechol related aromatics have been prepared and evaluated for antimicrobial activity. It turns out that these compounds have highly potent activity against Gram-negative bacteria, especially resistant pathogens such as Pseudomonas aeruginosa. The most active compound of the series was (6S,7S)-7-[2-(2-aminothiazol-4-yl)-2-[(Z)-[(1,5-dihydroxy-4-pyridon-2-yl)methoxy] imino]acetamido]-3-[[[(4-methyl-5-carboxymethyl)thiazol-2-yl]thio]methyl]-8-oxo-1-aza-4-thiabicyclo [4.2.0] oct-2-ene-2-carboxylic acid which exhibited potent in vitro activity against clinically isolated P. aeruginosa and Acinetobacter baumanii which is also resistant to many anti-infectives, and good in vivo efficacy against clinically isolated P. aeruginosa.