2. Academic Validation
  3. Design, synthesis and structure-activity relationships of 1,3,4-oxadiazole derivatives as novel inhibitors of glycogen synthase kinase-3beta

Design, synthesis and structure-activity relationships of 1,3,4-oxadiazole derivatives as novel inhibitors of glycogen synthase kinase-3beta

  • Bioorg Med Chem. 2009 Mar 1;17(5):2017-29. doi: 10.1016/j.bmc.2009.01.019.
Morihisa Saitoh 1,  Jun Kunitomo,  Eiji Kimura,  Yoji Hayase,  Hiromi Kobayashi,  Noriko Uchiyama,  Tomohiro Kawamoto,  Toshimasa Tanaka,  Clifford D Mol,  Douglas R Dougan,  Garret S Textor,  Gyorgy P Snell,  Fumio Itoh
Affiliations

Affiliation

  • 1 Pharmaceutical Research Division, Medicinal Chemistry Research Laboratories, Takeda Pharmaceutical Company, Ltd, Osaka, Japan. Saitoh_Morihisa@takeda.co.jp
PMID: 19200745 DOI: 10.1016/j.bmc.2009.01.019
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.

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