New broad-spectrum cephalosporins with anti-pseudomonal activity. I. Synthesis and antibacterial activity of 7 beta-[D-2-[(4-hydroxy-1,5-naphthyridine-3-carbonylamino)- and (4-hydroxypyridine-3-carbonylamino)]-2-(4-hydoxyphenyl)acetamido] cephalosporins.

The synthesis and the antibacterial activity of 7 beta-[D-2-[(4-hydroxy-1,5-naphthyridine-3-carbonylamino)- and (4-hydroxypyridine-3-carbonylamino)]-2-(4-hydroxyphenyl)acetamido]-cephalosporins with various substituents at the 3-position in the cephem nucleus are described. These compounds exhibited strong antibacterial activities against a variety of Gram-positive and Gram-negative bacteria, including Pseudomonas aeruginosa and Enterobacter aerogenes, which are insensitive to cefazolin and cefmetazole. The compounds (3e, 4e) having a 1-methyl-1H-tetrazolylthiomethyl group at the 3-position appeared to show the best activity in each series. The 4-hydroxypyridine-3-carbonylamino derivative 4e gave higher peak serum concentrations and urinary recovery rates than those of the 4-hydroxy-1,5-naphthyridine derivative 3e when administered subcutaneously to mice and intramuscularly to rats.