2. Academic Validation
  3. Quinolone derivatives containing strained spirocycle as orally active glycogen synthase kinase 3β (GSK-3β) inhibitors for type 2 diabetics

Quinolone derivatives containing strained spirocycle as orally active glycogen synthase kinase 3β (GSK-3β) inhibitors for type 2 diabetics

  • Bioorg Med Chem. 2012 Feb 1;20(3):1188-200. doi: 10.1016/j.bmc.2011.12.046.
Shigeki Seto 1,  Kazuhiko Yumoto,  Kyoko Okada,  Yoshikazu Asahina,  Aya Iwane,  Maki Iwago,  Reiko Terasawa,  Kevin R Shreder,  Koji Murakami,  Yasushi Kohno
Affiliations

Affiliation

  • 1 Discovery Research Laboratories, Kyorin Pharmaceutical Co., Ltd, 2399-1, Nogi, Nogi-machi, Shimotsuga-gun, Tochigi 329-0114, Japan. shigeki.seto@mb.kyorin-pharm.co.jp
PMID: 22261023 DOI: 10.1016/j.bmc.2011.12.046
Abstract

The design, synthesis, and evaluation of 6-6-7 tricyclic quinolones containing the strained spirocycle moiety aiming at the GSK-3β Inhibitor were described. Among the synthesized compounds, 44, having a cyclobutane ring on a spirocycle, showed excellent GSK-3β inhibitory activity in both cell-free and cell-based assays (IC(50) = 36nM, EC(50) = 3.2μM, respectively). Additionally, 44 decreased the plasma glucose concentration dose-dependently after an oral glucose tolerance test in mice.

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