Abstract
Using solid-phase, parallel-array synthesis, a series of urea-substituted thioisobutyric acids was synthesized and assayed for activity on the human PPAR subtypes. GW7647 (3) was identified as a potent human PPARalpha agonist with approximately 200-fold selectivity over PPARgamma and PPARdelta, and potent lipid-lowering activity in animal models of dyslipidemia. GW7647 (3) will be a valuable chemical tool for studying the biology of PPARalpha in human cells and animal models of disease.
MeSH terms
-
Animals
-
Butyrates / pharmacology
-
Cricetinae
-
Dietary Fats / pharmacology
-
Drug Design
-
Hyperlipidemias / blood
-
Hyperlipidemias / drug therapy
-
Hypolipidemic Agents / chemical synthesis*
-
Hypolipidemic Agents / pharmacology
-
Phenylurea Compounds / pharmacology
-
Receptors, Cytoplasmic and Nuclear / agonists*
-
Transcription Factors / agonists*
Substances
-
Butyrates
-
Dietary Fats
-
Hypolipidemic Agents
-
Phenylurea Compounds
-
Receptors, Cytoplasmic and Nuclear
-
Transcription Factors
-
GW 9578