PC-904, sodium 6-{ d (−)-α-(4-hydroxy-1,5-naphthyridine-3-carboxamido) phenylacetamido}-penicillanate, is a novel semisynthetic penicillin derivative that possesses a broad spectrum of in vitro and in vivo antibacterial activities. In low concentrations, PC-904 inhibits growth against large proportions of the gram-positive and gram-negative organisms susceptible to carbenicillin and gentamicin. In addition, PC-904 is several times more potent than carbenicillin against organisms such as Pseudomonas aeruginosa, Klebsiella pneumoniae, Escherichia coli, Proteus vulgaris, Shigella, Salmonella, Neisseria gonorrhoeae , and Bacteroides fragilis . Most striking are the inhibitory effects of PC-904 against P. aeruginosa and K. pneumoniae . Against these two clinical isolates, PC-904 is, respectively, 35 and 100 times more active than carbenicillin. The minimum inhibitory concentrations of PC-904 against P. aeruginosa are comparable to those of gentamicin. PC-904 acts bactericidally. The effect of inoculum size on the antibacterial activity is often small and generally comparable to carbenicillin. The rate of binding to serum protein is high (88 to 98%), but the effect of the addition of serum on the drug's activity is not marked, because such binding is reversible. It is confirmed that PC-904 has a very potent in vivo antibacterial activity against gram-negative and gram-positive organisms. Against systemic infections with P. aeruginosa, K. pneumoniae , and E. coli in mice, PC-904 is 7 to 10 times, over 8 times, and 2 to 15 times more active than carbenicillin, respectively.

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The synthesis and the antibacterial activity of 7;2-[D-2-[(4-hydroxy-1,5-naphthyridine-3carbonylamino)-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-I H-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.

A variety of 5‐mono‐ and 5,6‐disubstituted 1,4‐dihydro‐4‐oxonicotinates were prepared by a novel pyridine synthesis which involves thermal cyclisation of enaminomethylenemalonates 9. The intermediates 9 were readily prepared through a few steps from commercially available starting materials.