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.