New broad-spectrum cephalosporins with anti-pseudomonal activity. II. Synthesis and antibacterial activity of 7 beta-[2-acylamino-2-(4-hydroxyphenyl)acetamido]-3-[ (1-methyl-1H-tetrazol-5-yl)thiomethyl]ceph-3-em-4-carboxylic acids.

The influence of the chirality of the 7-acyl side chain and of various N-acyl moieties (A-CO-) on the in vitro activity of 7 beta-[2-acylamino-2-(4-hydroxyphenyl)acetamido ]-3-[(1-methyl-1H-tetrazol-5-yl)thiomethyl]ceph-3-em-4-carboxylic acids (6) was investigated. A cephalosporin having a 7-acyl side chain of S-configuration (6r) was only weakly active against Staphylococcus aureus and Klebsiella pneumoniae and was inactive against the other species tested. Among the various N-acyl moieties in the cephalosporins having a 7-acyl side chain of the R-configuration, the 4-hydroxypyridine-3-carbonyl moiety, unsubstituted or substituted with 5-bromo and/or 6-alkyl groups and the 4-hydroxy-1,5-naphthyridine-3-carbonyl moiety, unsubstituted or substituted with a 6-methyl and a 6-methoxy group gave the most active compounds. N-Ethylation of the 4-hydroxy-1,5-naphthyridine-3-carbonyl derivative and the 4-hydroxypyridine-3-carbonyl derivative (6p, 6q) resulted in a decrease of the in vitro activity.