STUDIES ON PYRIDONECARBOXYLIC ACIDS. 1. SYNTHESIS AND ANTIBACTERIAL EVALUATION OF 7-SUBSTITUTED-6-HALO-4-OXO-4H-THIAZETOQUINOLINE-3-CARBOXYLIC ACIDS
A series of thiazetoquinoline-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- derivative of 29a, was found to possess a favorable pharmacokinetic profile and oral activity superior to that of ciprofloxacin in experimental animals.