Discovery of a novel selective PPARgamma modulator from (-)-Cercosporamide derivatives.
Article Details
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Furukawa A, Arita T, Satoh S, Wakabayashi K, Hayashi S, Matsui Y, Araki K, Kuroha M, Ohsumi J
Discovery of a novel selective PPARgamma modulator from (-)-Cercosporamide derivatives.
Bioorg Med Chem Lett. 2010 Apr 1;20(7):2095-8. doi: 10.1016/j.bmcl.2010.02.073. Epub 2010 Feb 20.
- PubMed ID
- 20219371 [ View in PubMed]
- Abstract
In an investigation of (-)-Cercosporamide derivatives with a plasma glucose-lowering effect, we found that N-benzylcarboxamide derivative 4 was a partial agonist of PPARgamma. A SAR study of the substituents on carboxamide nitrogen afforded the N-(1-naphthyl)methylcarboxamide derivative 23 as the most potent selective PPARgamma modulator. An X-ray crystallography study revealed that compound 23 bounded to the PPARgamma ligand binding domain in a unique way without any interaction with helix12. Compound 23 displayed a potent plasma glucose-lowering effect in db/db mice without the undesirable increase in body fluid and heart weight that is typically observed when PPARgamma full agonists are administrated.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Pioglitazone Peroxisome proliferator-activated receptor gamma EC 50 (nM) 88 N/A N/A Details Rosiglitazone Peroxisome proliferator-activated receptor gamma EC 50 (nM) 11 N/A N/A Details