SYNTHESIS AND ANTIBACTERIAL ACTIVITY OF A NEW SERIES OF TETRACYCLIC PYRIDONE CARBOXYLIC-ACIDS

A series of novel tetracyclic pyridone carboxylic acids replacing the 10-position oxygen atom of yl)-5-oxo-5H-thiazolo[3,2-a]quinoline-4-car boxylic acid by imino groups (NR; R = Me, Et, c-Pr, allyl, Ph, benzyl) , a sulfur atom, or a carbonyl group was prepared and evaluated for an tibacterial activity and inhibitory activity on DNA gyrase isolated fr om E. coli KL-16. The in vitro antibacterial potency and DNA gyrase in hibitory activity were found to be in the following order: NMe greater -than-or-equal-to O > S >> C=O. Moreover, a methyl group was the optim al alkyl substituent at the 10-position nitrogen atom for antibacteria l activity and for DNA gyrase inhibitory activity. yl)-5-oxo-5H-thiazo lo[3,2-a]quinoline-4-carboxylic acid (10-NCH3) showed potent in vivo a ntibacterial activity.