Synthesis of ortho-functionalized 4-aminomethylpyridazines as substrate-like semicarbazide-sensitive amine oxidase inhibitors

Abstract

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.