Design, synthesis and structure-activity relationships of 1,3,4-oxadiazole derivatives as novel inhibitors of glycogen synthase kinase-3beta.
Basic Information
ID: ALA1152750
Journal: Bioorg Med Chem
Title: Design, synthesis and structure-activity relationships of 1,3,4-oxadiazole derivatives as novel inhibitors of glycogen synthase kinase-3beta.
Authors: Saitoh M, Kunitomo J, Kimura E, Hayase Y, Kobayashi H, Uchiyama N, Kawamoto T, Tanaka T, Mol CD, Dougan DR, Textor GS, Snell GP, Itoh F.
Abstract: Glycogen synthase kinase-3beta (GSK-3beta) is implicated in abnormal hyperphosphorylation of tau protein and its inhibitors are expected to be a promising therapeutic agents for the treatment of Alzheimer's disease. Here we report design, synthesis and structure-activity relationships of a novel series of oxadiazole derivatives as GSK-3beta inhibitors. Among these inhibitors, compound 20x showed highly selective and potent GSK-3beta inhibitory activity in vitro and its binding mode was determined by obtaining the X-ray co-crystal structure of 20x and GSK-3beta.
CiteXplore: 19200745
DOI: 10.1016/j.bmc.2009.01.019
Patent ID: ┄