Design, synthesis, and evaluation of potent, structurally novel peroxisome proliferator-activated receptor (PPAR) delta-selective agonists.

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Kasuga J, Nakagome I, Aoyama A, Sako K, Ishizawa M, Ogura M, Makishima M, Hirono S, Hashimoto Y, Miyachi H

Design, synthesis, and evaluation of potent, structurally novel peroxisome proliferator-activated receptor (PPAR) delta-selective agonists.

Bioorg Med Chem. 2007 Aug 1;15(15):5177-90. Epub 2007 May 13.

PubMed ID

17532641 [ View in PubMed

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Abstract

A series of 3-(4-alkoxyphenyl)propanoic acid derivatives was prepared as candidate peroxisome proliferator-activated receptor (PPAR) delta-selective agonists, based on our previously discovered potent human PPARalpha/delta dual agonist TIPP-401 as a lead compound. Structure-activity relationship studies clearly indicated the importance of the chain length of the alkoxy group at the 4-position, and the n-butoxy compound exhibited the most potent PPARdelta transactivation activity and highest PPARdelta selectivity. The (S)-enantiomer of a representative compound exhibited extremely potent PPARdelta transactivation activity, comparable with or somewhat superior to that of the known PPARdelta-selective agonist, GW-501516. The representative compound regulated the expression of genes involved in lipid and glucose homeostasis, and should be useful not only as a chemical tool to study PPARdelta function, but also as a candidate drug for the treatment of metabolic syndrome.

DrugBank Data that Cites this Article

Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Cardarine	Peroxisome proliferator-activated receptor alpha	EC 50 (nM)	1000	N/A	N/A	Details
Cardarine	Peroxisome proliferator-activated receptor delta	EC 50 (nM)	1.8	N/A	N/A	Details