Synthesis of ortho-Functionalized 4-Aminomethylpyridazines as Substrate-Like Semicarbazide-Sensitive Amine Oxidase Inhibitors

A series of 4-aminomethylpyridazines and -pyridazin-3(2H)-ones (“diaza-benzylamines”), bearing alkylamino side chains in ortho position relative to the CH2NH2 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.