Fluorinated pyrido[2,3-c]pyridazines. II. 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-fluoro-4(1H)-oxopyrido[2,3-c]pridazine-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-carbox ylate (7) or intramolecular cyclization of ethyl 2-(2,6-dichloro-5-fluoronicotinoyl)-2-[2-(p-fluorophenyl)hydraz ono]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.
Miyamoto
T
T
Research Laboratories, Dainippon Pharmaceutical Co., Ltd., Osaka, Japan.
Matsumoto
J
J
D042462:4-Quinolones; D000890:Anti-Infective Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D001419:Bacteria / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D011724:Pyridazines / Q000138:chemical synthesis* / Q000494:pharmacology; D011728:Pyridones / Q000138:chemical synthesis* / Q000494:pharmacology
D042462:4-Quinolones; D000890:Anti-Infective Agents; D011724:Pyridazines; D011728:Pyridones