Novel 2,3-Dihydrobenzofuran-2-carboxylic Acids: Highly Potent and Subtype-Selective PPARα Agonists with Potent Hypolipidemic Activity
| Autor: | Conrad Santini, Joel P. Berger, Guo Q. Shi, James V. Heck, Melba Hernandez, Raul F. Alvaro, Yong Zhang, Arun K. Agrawal, Soumya P. Sahoo, James F. Dropinski, Samuel D. Wright, Tian-Quan Cai, Gaochao Zhou, Peter T. Meinke, David E. Moller, Karen L. MacNaul |
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| Rok vydání: | 2005 |
| Předmět: |
Male
Transcriptional Activation Agonist medicine.drug_class Carboxylic acid Carboxylic Acids Molecular Conformation Hamster Hyperlipidemias In Vitro Techniques Chemical synthesis Radioligand Assay Structure-Activity Relationship chemistry.chemical_compound Dogs Cricetinae Drug Discovery medicine Animals Humans Potency PPAR alpha Triglycerides Benzofurans Hypolipidemic Agents chemistry.chemical_classification Fenofibrate Mesocricetus Chemistry Cholesterol Stereoisomerism In vitro Biochemistry Molecular Medicine medicine.drug |
| Zdroj: | Journal of Medicinal Chemistry. 48:5589-5599 |
| ISSN: | 1520-4804 0022-2623 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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