Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that govern lipid and glucose homeostasis, and play a central role in cardiovascular disease, obesity, and diabetes. Thus, there is significant interest in developing new and specific agonists for these receptors. Herein we present screening results for a series of chiral phenoxyacetic acid analogues, some of which are potent PPARalpha agonists as well as PPARgamma agonists. The stereochemistry of these compounds plays an important role in determining their activity; the S isomers were observed to be more active than the corresponding R isomers. Interestingly, for one of these analogues, the stereoselectivity toward PPARalpha was reversed, and for this reason docking experiments were performed to rationalize this peculiar behavior.

Synthesis, Biological Evaluation and Molecular Modeling Investigation of Chiral Phenoxyacetic Acid Analogues with PPARalfa and PPARgamma Agonist Activity / G., Fracchiolla; A., Laghezza; L., Piemontese; G., Carbonara; Lavecchia, Antonio; P., Tortorella; M., Crestani; Novellino, Ettore; F., Loiodice. - In: CHEMMEDCHEM. - ISSN 1860-7179. - ELETTRONICO. - 2:(2007), pp. 641-654. [10.1002/cmdc.200600307]

Synthesis, Biological Evaluation and Molecular Modeling Investigation of Chiral Phenoxyacetic Acid Analogues with PPARalfa and PPARgamma Agonist Activity

LAVECCHIA, ANTONIO;NOVELLINO, ETTORE;
2007

Abstract

Peroxisome proliferator-activated receptors (PPARs) are ligand-activated transcription factors that govern lipid and glucose homeostasis, and play a central role in cardiovascular disease, obesity, and diabetes. Thus, there is significant interest in developing new and specific agonists for these receptors. Herein we present screening results for a series of chiral phenoxyacetic acid analogues, some of which are potent PPARalpha agonists as well as PPARgamma agonists. The stereochemistry of these compounds plays an important role in determining their activity; the S isomers were observed to be more active than the corresponding R isomers. Interestingly, for one of these analogues, the stereoselectivity toward PPARalpha was reversed, and for this reason docking experiments were performed to rationalize this peculiar behavior.
2007
Synthesis, Biological Evaluation and Molecular Modeling Investigation of Chiral Phenoxyacetic Acid Analogues with PPARalfa and PPARgamma Agonist Activity / G., Fracchiolla; A., Laghezza; L., Piemontese; G., Carbonara; Lavecchia, Antonio; P., Tortorella; M., Crestani; Novellino, Ettore; F., Loiodice. - In: CHEMMEDCHEM. - ISSN 1860-7179. - ELETTRONICO. - 2:(2007), pp. 641-654. [10.1002/cmdc.200600307]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11588/201569
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