SYNTHESIS AND ANTIBACTERIAL ACTIVITIES OF NOVEL DIHYDROOXAZINE AND DIHYDROTHIAZINE RING-FUSED TRICYCLIC QUINOLONECARBOXYLIC ACIDS - 9-FLUORO-3-METHYLENE-10-(4-METHYLPIPERAZIN-1-YL)-7-OXO-2,3-DIHYDRO-7H-PYRIDO[1,2,3-DE][1,4]BENZOXAZINE-6-CARBOXYLIC ACID AND ITS 1-THIA CONGENER

A new synthetic method was developed to obtain two novel tricyclic quinolonecarboxylic acids, 9-fluoro-3-methylene-10-(4-methylpiperazin-1-yl)-7-oxo-2,3-dihydro-7H-pyrido[1,2,3-de][1,4]benzoxazine-6-carboxylic acid (2) and its 1-thia congener 3. The method involves the key intermediate of an oxetane derivative and its cleavage with acids. Evaluation of the antibacterial activities showed that 2 and 3 are excellent against both Gram-positive and Gram-negative organisms in vitro, being comparable to or only slightly less effective than Ofloxacin. In experimental systemic infections in mice, compound 2 showed distinctly higher activity than Ofloxacin, especially against infection caused by Escherichia coli.