RESUMO
A series of polyfluoro-3-quinolonecarboxylic acids have been synthesized and their in vitro antibacterial activity evaluated. The desired 7-(substituted amino) derivatives were prepared from the 5,6,7,8-tetrafluoroquinolone acids. Conversely, amine displacement occurred primarily at the 5-position when the ester was used. Structure-activity studies indicated that the antibacterial activity was greatest when the N-1 substituent was cyclopropyl and the 7-substituent was 4-methyl-1-piperazinyl. All 5-(substituted amino) derivatives showed poor in vitro activity.
Assuntos
Ciprofloxacina/análogos & derivados , Norfloxacino/análogos & derivados , Animais , Fenômenos Químicos , Química , Ciprofloxacina/síntese química , Ciprofloxacina/farmacologia , Enterobacter/efeitos dos fármacos , Enterococcus faecalis/efeitos dos fármacos , Escherichia coli/efeitos dos fármacos , Infecções por Escherichia coli/tratamento farmacológico , Klebsiella pneumoniae/efeitos dos fármacos , Espectroscopia de Ressonância Magnética , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Norfloxacino/síntese química , Norfloxacino/farmacologia , Pseudomonas aeruginosa/efeitos dos fármacos , Serratia marcescens/efeitos dos fármacos , Infecções Estafilocócicas/tratamento farmacológico , Staphylococcus aureus/efeitos dos fármacos , Relação Estrutura-AtividadeRESUMO
The synthesis of a series of 6-(substituted-phenyl)-1,2,4-triazolo[4,3-b]pyridazines (VIII) is reported. Some of these derivatives show activity in tests predictive of anxiolytic activity [(a) protection against pentylenetetrazole-induced convulsions; (b) thirsty rat conflict procedure]. They also represent a new class of compound which inhibits [3H]diazepam binding. Structure--activity correlations, as well as the ability of structures VIII to inhibit [3H]diazepam binding (in vitro), are discussed.