title: 3-[5-(4,5-dihydro-1H-imidazol-2-yl)-furan-2-yl]phenylamine (Amifuraline), a promising reversible and selective peripheral MAO-A inhibitor.
abstract: On the basis of the observation that the central side effects of MAO inhibitors may represent a major limit for their use in pathological processes involving peripheral MAOs, we investigated the possibility of generating novel inhibitors able to target specifically peripheral MAOs. To address this issue, we designed compounds 7-28. From biological results, the 2-(5-phenyl-furan-2-yl)-4,5-dihydro-1H-imidazole (Furaline, 17) proved to be a suitable lead. In fact, in enzyme assays on homogenate preparation from rat liver and HEK cells expressing MAO-A or MAO-B, compounds possessing the frame of 17 behaved as selective and reversible MAO-A inhibitors. Interestingly, in in vivo studies the amino derivative 21 (Amifuraline), endowed with good hydrophilic character, was able to significantly inhibit liver but not brain MAO-A.
authors.affiliation: Dipartimento di Scienze Chimiche, Università degli Studi di Camerino, via S. Agostino 1, 62032 Camerino, Italy.
authors.forename: Francesco
authors.initials: F
authors.lastname: Gentili
authors.forename: Nathalie
authors.initials: N
authors.lastname: Pizzinat
authors.forename: Catherine
authors.initials: C
authors.lastname: Ordener
authors.forename: Sophie
authors.initials: S
authors.lastname: Marchal-Victorion
authors.forename: Agnès
authors.initials: A
authors.lastname: Maurel
authors.forename: Robert
authors.initials: R
authors.lastname: Hofmann
authors.forename: Pierre
authors.initials: P
authors.lastname: Renard
authors.forename: Philippe
authors.initials: P
authors.lastname: Delagrange
authors.forename: Maria
authors.initials: M
authors.lastname: Pigini
authors.forename: Angelo
authors.initials: A
authors.lastname: Parini
authors.forename: Mario
authors.initials: M
authors.lastname: Giannella
mesh_terms: D000814:Aniline Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D001921:Brain / Q000201:enzymology; D002460:Cell Line; D005663:Furans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D007527:Isoenzymes / Q000037:antagonists & inhibitors; D008099:Liver / Q000201:enzymology; D008297:Male; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009928:Organ Specificity; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000814:Aniline Compounds; D005663:Furans; D007093:Imidazoles; D007527:Isoenzymes; D008996:Monoamine Oxidase Inhibitors; C514068:amifuraline