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

Norbert Haider; Iris Hochholdinger; Péter Mátyus; Andrea Wobus

doi:10.1248/cpb.58.964

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

Norbert Haider, Iris Hochholdinger, Péter Mátyus, Andrea Wobus

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Keywords: 4-aminomethylpyridazine, diaza-benzylamine, selective debenzylation, semicarbazide-sensitive amine oxidase/vascular adhesion protein 1, semicarbazide-sensitive amine oxidase inhibitor

JOURNAL FREE ACCESS

2010 Volume 58 Issue 7 Pages 964-970

DOI https://doi.org/10.1248/cpb.58.964

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Abstract

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.

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