Novel 2,3-Dihydrobenzofuran-2-carboxylic Acids: Highly Potent and Subtype-Selective PPARα Agonists with Potent Hypolipidemic Activity
Journal of Medicinal Chemistry2005Vol. 48(17), pp. 5589–5599
Citations Over TimeTop 19% of 2005 papers
Guo Q. Shi, James F. Dropinski, Yong Zhang, Conrad Santini, Soumya P. Sahoo, Joel P. Berger, Karen L. MacNaul, Gaochao Zhou, Arun K. Agrawal, Raúl Álvaro, Tian‐Quan Cai, Melba Hernandez, Samuel D. Wright, David E. Moller, James V. Heck, Peter T. Meinke
Abstract
The design and synthesis of a novel class of 2,3-dihydrobenzofuran-2-carboxylic acids as highly potent and subtype-selective PPARalpha agonists are reported. Systematic study of structure-activity relationships has identified several key structural elements within this class for maintaining the potency and subtype selectivity. Select compounds were evaluated in animal models of dyslipidemia using Syrian hamsters and male Beagle dogs, and all these compounds displayed excellent cholesterol- and triglyceride-lowering activity at dose levels that were much lower than the marketed weak PPARalpha agonist fenofibrate.
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