STUDIES ON PYRIDONECARBOXYLIC ACIDS. 1. SYNTHESIS AND ANTIBACTERIAL EVALUATION OF 7-SUBSTITUTED-6-HALO-4-OXO-4H-THIAZETOQUINOLINE-3-CARBOXYLIC ACIDS

Article abstract of DOI:10.1021/jm00103a011

A series of <1,3>thiazeto<3,2-a>quinoline-3-carboxylic acids and their esters were prepared and evaluated for antibacterial activity.The derivatives with a hydrogen or methyl group at C-1, fluorine at C-6, and piperazinyl or 4-methyl-1-piperazinyl group at C-7 showed superior in vitro antibacterial activity, and the derivatives with 4-methyl-1-piperazinyl group at C-7 had potent in vivo activity.Compound 29a (NM394) showed excellent in vitro antibacterial activity and low toxicity but poor absorption from the gastrointestinal tract.Compound 29ee (NM441), an N-<(5-methyl-2-oxo-1,3-dioxol-4-yl)methyl> derivative of 29a, was found to possess a favorable pharmacokinetic profile and oral activity superior to that of ciprofloxacin in experimental animals.