title: Alkylamino derivatives of 4-aminomethylpyridine as inhibitors of copper-containing amine oxidases.
abstract: The first substratelike, reversible inhibitors of different copper amine oxidases (CAOs) with IC50 (M) as low as 2.0 x 10(-8) corresponding to derivatives of 4-aminomethylpyridine with alkoxy (1a-d), alkylthio (2a,b), and alkylamino (3a-e, 4a-j) groups in the positions 3 and 5 have been prepared and studied. The inhibitors 1a-d are active on benzylamine oxidase and semicarbazide-sensitive amine oxidase and are very selective with respect to diamine oxidase, lysyl oxidase, and monoamine oxidases. The inhibitors 2a,b are selective for benzylamine oxidase whereas 2a is also a new type of good substrate of diamine oxidase. The inhibitors 3a-e and 4a-j are substratelike, reversible, nonselective inhibitors of various CAOs including pea seedling amine oxidase and Hansenula polymorpha amine oxidase, whose enzymatic sites are known from X-ray structure determinations. The inhibitors 3b,c and 4b,c are excellent substratelike tools for studies correlating CAOs that afford crystals suitable for X-ray structure determinations with CAOs from mammals.
authors.affiliation: Dipartimento di Chimica e Tecnologie Farmaceutiche e Alimentari, Università di Genova, Via Brigata Salerno, 16147 Genova, Italy. bertini@dictfa.unige.it
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Bertini
authors.forename: Franca
authors.initials: F
authors.lastname: Buffoni
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ignesti
authors.forename: Nevio
authors.initials: N
authors.lastname: Picci
authors.forename: Sonia
authors.initials: S
authors.lastname: Trombino
authors.forename: Francesca
authors.initials: F
authors.lastname: Iemma
authors.forename: Silvana
authors.initials: S
authors.lastname: Alfei
authors.forename: Marco
authors.initials: M
authors.lastname: Pocci
authors.forename: Francesco
authors.initials: F
authors.lastname: Lucchesini
authors.forename: Angela
authors.initials: A
authors.lastname: De Munno
mesh_terms: D006631:Amine Oxidase (Copper-Containing) / Q000037:antagonists & inhibitors* / Q000737:chemistry; D000818:Animals; D007700:Kinetics; D007928:Lethal Dose 50; D051379:Mice; D011725:Pyridines / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D013329:Structure-Activity Relationship; D023382:Toxicity Tests, Acute
chemical_list: D011725:Pyridines; D006631:Amine Oxidase (Copper-Containing)