RESUMO
A series of 4-aminomethylpyridazines and -pyridazin-3(2H)-ones ("diaza-benzylamines"), bearing alkylamino side chains in ortho position relative to the CH(2)NH(2) unit, was synthesized by catalytic hydrogenation of the corresponding nitriles in strongly acidic medium. N-Benzyl protecting groups either at the pyridazinone ring nitrogen or at an exocyclic nitrogen were selectively removed hydrogenolytically or by treatment with a Lewis acid. The new compounds were tested in vitro for semicarbazide-sensitive amine oxidase (SSAO) inhibitory activity and 4-(aminomethyl)-N,N'-diethylpyridazine-3,5-diamine (22) was found to be the most active representative.
Assuntos
Amina Oxidase (contendo Cobre)/antagonistas & inibidores , Diaminas/química , Inibidores Enzimáticos/síntese química , Piridazinas/química , Amina Oxidase (contendo Cobre)/genética , Amina Oxidase (contendo Cobre)/metabolismo , Diaminas/síntese química , Diaminas/farmacologia , Inibidores Enzimáticos/química , Humanos , Piridazinas/síntese química , Piridazinas/farmacologia , Proteínas Recombinantes/antagonistas & inibidores , Proteínas Recombinantes/genética , Proteínas Recombinantes/metabolismoRESUMO
Reaction of the title compound with hydrazine in the presence of air gives the 1-unsubstituted parent system via oxidative dehydrazination of the 1-hydrazino intermediate. The latter can be obtained in high yield by carrying out the hydrazinolysis step under inert gas, and it is smoothly converted into [1,2,4]-triazolo[4',3':1,6]pyridazino[4,5- b]indoles.
