title: Synthesis and evaluation of iodinated benzamide derivatives as selective and reversible monoamine oxidase B inhibitors.
abstract: A new series of iodinated analogues of N-(2-aminoethyl)benzamide was synthesized and evaluated for inhibitory potency and specificity toward monoamine oxidase type-B (MAO-B). Among them, N-(2-aminoethyl)-2-chloro-4-iodobenzamide hydrochloride (2d) showed high inhibitory potency and selectivity against MAO-B. The type of MAO-B inhibition by 2d was non-competitive and the inhibition constant (Ki) was 0.80 microM. Strong and selective in vivo MAO-B inhibition by 2d was also confirmed. The brain MAO-B inhibition by 2d was reversible and the enzyme activity completely returned to the control value 24 h after administration. Compound 2d was, therefore, considered to be a candidate for advanced development as a radioiodinated ligand that may be useful for functional MAO-B studies in the living brain using single photon emission computer tomography.
authors.affiliation: Osaka University of Pharmaceutical Sciences, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ohmomo
authors.forename: K
authors.initials: K
authors.lastname: Murakami
authors.forename: M
authors.initials: M
authors.lastname: Hirata
authors.forename: A
authors.initials: A
authors.lastname: Sugimoto
authors.forename: Y
authors.initials: Y
authors.lastname: Magata
authors.forename: N
authors.initials: N
authors.lastname: Miyahara
authors.forename: C
authors.initials: C
authors.lastname: Tanaka
authors.forename: A
authors.initials: A
authors.lastname: Yokoyama
mesh_terms: D000818:Animals; D001549:Benzamides / Q000138:chemical synthesis* / Q000494:pharmacology; D001921:Brain / Q000201:enzymology; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D008996:Monoamine Oxidase Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D001549:Benzamides; D008996:Monoamine Oxidase Inhibitors