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 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.
Haider
Norbert
N
Department of Drug and Natural Product Synthesis, Faculty of Life Sciences, University of Vienna, Vienna, Austria. norbert.haider@univie.ac.at
Hochholdinger
Iris
I
Mátyus
Péter
P
Wobus
Andrea
A
D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism; D003959:Diamines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry; D006801:Humans; D011724:Pyridazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D011994:Recombinant Proteins / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
C552651:4-(aminomethyl)-N,N'-diethylpyridazine-3,5-diamine; D003959:Diamines; D004791:Enzyme Inhibitors; D011724:Pyridazines; D011994:Recombinant Proteins; D006631:Amine Oxidase (Copper-Containing)