Design and Synthesis of Dual Peroxisome Proliferator-Activated Receptors γ and δ Agonists as Novel Euglycemic Agents with a Reduced Weight Gain Profile
Journal of Medicinal Chemistry2006Vol. 49(19), pp. 5649–5652
Citations Over TimeTop 12% of 2006 papers
Yanping Xu, Garret J. Etgen, Carol L. Broderick, Emily J. Canada, Isabel González‐Álvarez, Jason Lamar, Chahrzad Montrose‐Rafizadeh, Brian A. Oldham, John J. Osborne, Chaoyu Xie, Qing Shi, Leonard L. Winneroski, Jeremy S. York, Nathan Yumibe, Richard W. Zink, Nathan B. Mantlo
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.
Related Papers
- → FDA Lifts Restrictions on Rosiglitazone(2014)2 cited
- → Rosiglitazone and Cardiovascular Risk – A Review(2012)
- Rosiglitazone compound formula eliminates the side effects of rosiglitazone(2014)
- The progress of clinical study on rosiglitazone(2003)
- → Re-evaluation of the cardiovascular safety of rosiglitazone(2014)