Synthesis and biological evaluation of novel (-)-Cercosporamide derivatives as potent selective PPARgamma modulators.

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Furukawa A, Arita T, Fukuzaki T, Mori M, Honda T, Satoh S, Matsui Y, Wakabayashi K, Hayashi S, Nakamura K, Araki K, Kuroha M, Tanaka J, Wakimoto S, Suzuki O, Ohsumi J

Synthesis and biological evaluation of novel (-)-Cercosporamide derivatives as potent selective PPARgamma modulators.

Eur J Med Chem. 2012 Aug;54:522-33. doi: 10.1016/j.ejmech.2012.05.040. Epub 2012 Jun 7.

PubMed ID

22727448 [ View in PubMed

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Abstract

Selective peroxisome proliferator-activated receptor gamma (PPARgamma) modulators are expected to be a novel class of drugs improving plasma glucose levels without PPARgamma-related adverse effects. As a continuation of our studies for (-)-Cercosporamide derivatives as selective PPARgamma modulators, we synthesized substituted naphthalene type compounds and identified the most potent compound 15 (EC(50) = 0.94 nM, E(max) = 38%). Compound 15 selectively activated PPARgamma transcription and did not activate PPARalpha and PPARdelta. The potassium salt of compound 15 showed a high solubility and a good oral bioavailability (58%). Oral administration of the potassium salt remarkably improved the plasma glucose levels of female Zucker diabetic fatty rats at 1 mg/kg. Moreover, it did not cause a plasma volume increase or a cardiac enlargement in Wistar-Imamichi rats, even at 100 mg/kg.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Rosiglitazone	Peroxisome proliferator-activated receptor gamma	EC 50 (nM)	11	N/A	N/A	Details