Novel 2,3-dihydrobenzofuran-2-carboxylic acids: Highly potent and subtype-selective PPARα agonists with potent hypolipidemic activity
The design and synthesis of a novel class of 2,3-dihydrobenzofuran-2- carboxylic acids as highly potent and subtype-selective PPARα 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 PPARα agonist fenofibrate.
Shi, Guo Q.,Dropinski, James F.,Zhang, Yong,Santini, Conrad,Sahoo, Soumya P.,Berger, Joel P.,MacNaul, Karen L.,Zhou, Gaochao,Agrawal, Arun,Alvaro, Raul,Cai, Tian-Quan,Hernandez, Melba,Wright, Samuel D.,Moller, David E.,Heck, James V.,Meinke, Peter T.
p. 5589 - 5599
(2007/10/03)
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