Discovery of a novel class of 1,3-dioxane-2-carboxylic acid derivatives as subtype-selective peroxisome proliferator-activated receptor alpha (PPARalpha) agonists.

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Aoki T, Asaki T, Hamamoto T, Sugiyama Y, Ohmachi S, Kuwabara K, Murakami K, Todo M

Discovery of a novel class of 1,3-dioxane-2-carboxylic acid derivatives as subtype-selective peroxisome proliferator-activated receptor alpha (PPARalpha) agonists.

Bioorg Med Chem Lett. 2008 Mar 15;18(6):2128-32. doi: 10.1016/j.bmcl.2008.01.086. Epub 2008 Jan 30.

PubMed ID

18280733 [ View in PubMed

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Abstract

A new series of 1,3-dioxane-2-carboxylic acid derivatives was synthesized and evaluated for agonist activity at human peroxisome proliferator-activated receptor (PPAR) subtypes. Structure-activity relationship studies led to the identification of 2-methyl-c-5-[4-(5-methyl-2-phenyl-1,3-oxazol-4-yl)butyl]-1,3-dioxane-r-2-carboxy lic acid 4b as a potent PPARalpha agonist with high subtype selectivity at human receptor subtypes. This compound exhibited a substantial hypolipidemic effect in type 2 diabetic KK-A(y) mice.

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Binding Properties

Drug	Target	Property	Measurement	pH	Temperature (°C)
Bezafibrate	Peroxisome proliferator-activated receptor alpha	EC 50 (nM)	30000	N/A	N/A	Details
Bezafibrate	Peroxisome proliferator-activated receptor delta	EC 50 (nM)	30000	N/A	N/A	Details
Bezafibrate	Peroxisome proliferator-activated receptor gamma	EC 50 (nM)	100000	N/A	N/A	Details