title: Synthesis and Biochemical Testing of 3-(Carboxyphenylethyl)imidazo[2,1-f][1,2,4]triazines as Inhibitors of AMP Deaminase.
abstract: C-Ribosyl imidazo[2,1-f][1,2,4]triazines and 3-[2-(3-carboxyphenyl)ethyl]-3,6,7,8-tetrahydroimidazo[4,5-d][1,3]diazepin-8-ols represent two classes of known AMP deaminase inhibitors. A combination of the aglycone from the former class with the ribose phosphate mimic from the latter led to the 3-[2-(3-carboxyphenyl)ethyl]imidazo[2,1-f][1,2,4]triazines, which represent a new class of AMP deaminase inhibitors. The best compound, 3-[2-(3-carboxy-5,6,7,8-tetrahydronaphthyl)ethyl]imidazo[2,1-f][1,2,4]triazine (8), was a good inhibitor of all three human AMPD recombinant isozymes (AMPD1, AMPD2, and AMPD3; IC50 = 0.9-5.7 μM) but a poor inhibitor of the plant recombinant enzyme (Arabidopsis FAC1; IC50 = 200 μM).
authors.affiliation: Bayer CropScience AG, Werk Höchst, G836, D-65926 Frankfurt am Main, Germany.
authors.forename: Stephen D
authors.initials: SD
authors.lastname: Lindell
authors.affiliation: Bayer CropScience AG, Werk Höchst, G836, D-65926 Frankfurt am Main, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Maechling
authors.affiliation: Department of Biomedical Sciences, Oakland University William Beaumont School of Medicine, Rochester, Michigan 48309.
authors.forename: Richard L
authors.initials: RL
authors.lastname: Sabina
keywords: AMP-deaminase; AMPD inhibition; AMPD inhibitor; adenylate-deaminase; imidazotriazine