Synthesis and antibacterial evaluation of 1,2,3,4-tetrahydro-4-oxo-1,8-naphthyridine-3-carboxylic acid esters, carbonitriles, and carboxamides.
A series of 1,2,3,4-tetrahydro-4-oxo-1,8-naphthyridine-3-carboxylic acid esters, carbonitriles, and carboxamides (2a-k) was synthesized and initially evaluated (dose range 50-400 mg/kg) in mice infected with Escherichia coli. Only two derivatives, the ethyl and butyl esters of 1-ethyl-1,2-dihydro-4-hydroxy-7-methyl-1,8-naphthyridine-3-carboxylic acid, protected the animals against E. coli and several other gram-negative bacterial pathogenic infections. A pro-drug type of mechanism appears to be operable since neither agent showed in vitro activity.
D000577:Amides / Q000138:chemical synthesis / Q000494:pharmacology; D000900:Anti-Bacterial Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002264:Carboxylic Acids / Q000138:chemical synthesis / Q000494:pharmacology; D004926:Escherichia coli / Q000187:drug effects; D004952:Esters; D008826:Microbial Sensitivity Tests; D009287:Naphthyridines / Q000138:chemical synthesis* / Q000494:pharmacology; D009570:Nitriles / Q000138:chemical synthesis / Q000494:pharmacology; D011513:Proteus mirabilis / Q000187:drug effects; D011514:Proteus vulgaris / Q000187:drug effects; D012485:Salmonella typhi / Q000187:drug effects; D012486:Salmonella typhimurium / Q000187:drug effects
D000577:Amides; D000900:Anti-Bacterial Agents; D002264:Carboxylic Acids; D004952:Esters; D009287:Naphthyridines; D009570:Nitriles