STUDIES ON β-LACTAM ANTIBIOTICS: I. SYNTHESIS AND IN VITRO ANTI-PSEUDOMONAL ACTIVITY OF 3-ISOTHIAZOLE-CEPHALOSPORIN DERIVATIVES

The synthesis and in vitro activity of 7β-[(Z)-2-(2-amino-4-thiazolyl)-2-(2-carboxy-2-alkoxyimino)acetamido]cephalosporins with a (4-carboxy-3-hydroxy-5-isothiazolyl)thiomethyl group at the 3-position are described. These cephalosporins (9a-9i) showed excellent activity against Gram-negative bacteria including β-lactamase producing strains. The most interesting compound of the series was 7β-[(Z)-2-(2-amino-4-thiazolyl)-2-(2-carboxy-2-propoxyimino)acetamido]-3-cephem-4-carboxylic acid (9g, YM-13115) because of its outstanding inhibitory potency against Pseudomonas aeruginosa and highly prolonged plasma half-life in rats.