FLUORINATED PYRIDO[2,3-C]PYRIDAZINES .2. SYNTHESIS AND ANTIBACTERIAL ACTIVITY OF 1,7-DISUBSTITUTED 6-FLUORO-4(1H)-OXOPYRIDO[2,3-C]PYRIDAZINE-3-CARBOXYLIC ACIDS

Chemical modification of pyridonecarboxylic acid antibacterials with a 1,8-naphthyridine ring, such as enoxacin and tosufloxacin, to their 2-aza derivatives was studied. A new series of 1,7-disubstituted 6-fluro-4(1H)-oxopyrido[2, 3-c]pyridazine-3-carboxylic acids (25-27) was prepared by a route involving either alkylation of ethyl 6-fluoro-4(1H)-oxo-7-(p-tolylthio)pyrido[2, 3-c]pyridazine-3-carboxylate (7) or intramolecular cyclization of ethyl 2-(2,6-dichloro-5-fluoronicotinoyl)-2-[2-(p-fluorophenyl) hydrazono]acetate (20), followed by displacement reaction with cyclic amines at C-7; the N-1 substituent in these compounds included of ethyl, 2-fluoroethyl and p-fluorophenyl groups, and the C-7 functional group comprised variously-substituted piperazines and pyrrolidines. Antibacterial activities of these compounds were markedly inferior to those of enoxacin and tosufloxacin.