Design, synthesis, and evaluation of substituted phenylpropanoic acid derivatives as human peroxisome proliferator activated receptor activators. Discovery of potent and human peroxisome proliferator activated receptor alpha subtype-selective activators.
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Nomura M, Tanase T, Ide T, Tsunoda M, Suzuki M, Uchiki H, Murakami K, Miyachi H
Design, synthesis, and evaluation of substituted phenylpropanoic acid derivatives as human peroxisome proliferator activated receptor activators. Discovery of potent and human peroxisome proliferator activated receptor alpha subtype-selective activators.
J Med Chem. 2003 Aug 14;46(17):3581-99.
- PubMed ID
- 12904063 [ View in PubMed]
- Abstract
Substituted phenylpropanoic acid derivatives were prepared as part of a search for subtype-selective human peroxisome proliferator activated receptor alpha (PPARalpha) activators. Structure-activity relationship studies indicated that the nature and the stereochemistry of the substituent at the alpha-position of the head part containing the carboxyl group, the distance between the carboxyl group and the central benzene ring, the linking group between the central benzene ring and the distal benzene ring, and the substituent at the distal hydrophobic tail part of the molecule all play key roles in determining the potency and selectivity of PPAR subtype transactivation. This study has led to the identification of potent and human PPARalpha selective optically active alpha-alkylphenylpropanoic acid derivatives, which will be useful not only as pharmacological tools to investigate the physiology and pathophysiology of PPARalpha but also as candidate drugs for the treatment of altered metabolic homeostasis, such as dyslipidemia, obesity, and diabetes.
DrugBank Data that Cites this Article
- Binding Properties
Drug Target Property Measurement pH Temperature (°C) Bezafibrate Peroxisome proliferator-activated receptor alpha EC 50 (nM) >78000 N/A N/A Details Bezafibrate Peroxisome proliferator-activated receptor delta EC 50 (nM) >143000 N/A N/A Details Bezafibrate Peroxisome proliferator-activated receptor gamma EC 50 (nM) >137000 N/A N/A Details Fenofibrate Peroxisome proliferator-activated receptor alpha EC 50 (nM) 41000 N/A N/A Details Fenofibrate Peroxisome proliferator-activated receptor alpha EC 50 (nM) 50000 N/A N/A Details