Design and synthesis of dual peroxisome proliferator-activated receptors gamma and delta agonists as novel euglycemic agents with a reduced weight gain profile.

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Xu Y, Etgen GJ, Broderick CL, Canada E, Gonzalez I, Lamar J, Montrose-Rafizadeh C, Oldham BA, Osborne JJ, Xie C, Shi Q, Winneroski LL, York J, Yumibe N, Zink R, Mantlo N

Design and synthesis of dual peroxisome proliferator-activated receptors gamma and delta agonists as novel euglycemic agents with a reduced weight gain profile.

J Med Chem. 2006 Sep 21;49(19):5649-52.

PubMed ID

16970391 [ View in PubMed

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Abstract

The design and synthesis of the dual peroxisome proliferator-activated receptor (PPAR) gamma/delta agonist (R)-3-{4-[3-(4-chloro-2-phenoxy-phenoxy)-butoxy]-2-ethyl-phenyl}-propionic acid (20) for the treatment of type 2 diabetes and associated dyslipidemia is described. The compound possesses a potent dual hPPAR gamma/delta agonist profile (IC(50) = 19 nM/4 nM; EC(50) = 102 nM/6 nM for hPPARgamma and hPPARdelta, respectively). In preclinical models, the compound improves insulin sensitivity and reverses diabetic hyperglycemia with less weight gain at a given level of glucose control relative to rosiglitazone.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Rosiglitazone	Peroxisome proliferator-activated receptor gamma	EC 50 (nM)	308	N/A	N/A	Details
Rosiglitazone	Peroxisome proliferator-activated receptor gamma	IC 50 (nM)	67	N/A	N/A	Details