Quinolone derivatives containing strained spirocycle as orally active glycogen synthase kinase 3β (GSK-3β) inhibitors for type 2 diabetics
| Autor: | Kazuhiko Yumoto, Koji Murakami, Shigeki Seto, Reiko Terasawa, Yasushi Kohno, Kevin R. Shreder, Aya Iwane, Yoshikazu Asahina, Maki Iwago, Kyoko Okada |
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| Rok vydání: | 2011 |
| Předmět: |
Male
Models Molecular medicine.drug_class Clinical Biochemistry Pharmaceutical Science Quinolones Biochemistry Cyclobutane chemistry.chemical_compound Glycogen Synthase Kinase 3 Mice GSK-3 Drug Discovery medicine Moiety Animals Humans Spiro Compounds Molecular Biology IC50 EC50 chemistry.chemical_classification Glycogen Synthase Kinase 3 beta Organic Chemistry Hep G2 Cells Glucose Tolerance Test Quinolone Orally active chemistry Diabetes Mellitus Type 2 Drug Design Molecular Medicine Tricyclic |
| Zdroj: | Bioorganicmedicinal chemistry. 20(3) |
| ISSN: | 1464-3391 |
| Popis: | 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 (IC50 = 36 nM, EC50 = 3.2 μM, respectively). Additionally, 44 decreased the plasma glucose concentration dose-dependently after an oral glucose tolerance test in mice. |
| Databáze: | OpenAIRE |
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