Synthesis and evaluation of iodinated benzamide derivatives as selective and reversible monoamine oxidase B inhibitors.
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.
Ohmomo
Y
Y
Osaka University of Pharmaceutical Sciences, Japan.
Murakami
K
K
Hirata
M
M
Sugimoto
A
A
Magata
Y
Y
Miyahara
N
N
Tanaka
C
C
Yokoyama
A
A
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
D001549:Benzamides; D008996:Monoamine Oxidase Inhibitors