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• W2044749519 abstract "A series of 1,3-dioxane carboxylic acid derivatives was synthesized and evaluated for human PPAR transactivation activity. Structure–activity relationships on the phenyloxazole moiety of the lead compound 3 revealed that the introduction of small hydrophobic substituents at the 4-position of the terminal phenyl ring increased the PPARα agonist activity, and that the oxazole heterocycle was essential to the maintenance of both potency and PPARα subtype-selectivity. This investigation led to the identification of 14d (NS-220) and 14i as highly potent and selective human PPARα agonists. In KK-Ay type 2 diabetic mice, these compounds significantly lowered plasma triglyceride and very-low-density plus low-density lipoprotein cholesterol levels while simultaneously raising HDL cholesterol levels. Our results suggest that highly potent and subtype-selective PPARα agonists will be promising drugs for the treatment of metabolic disorders in type 2 diabetes." @default.
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• W2044749519 date "2008-01-01" @default.
• W2044749519 modified "2023-10-02" @default.
• W2044749519 title "Structure–activity studies on 1,3-dioxane-2-carboxylic acid derivatives, a novel class of subtype-selective peroxisome proliferator-activated receptor α (PPARα) agonists" @default.
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• W2044749519 doi "https://doi.org/10.1016/j.bmc.2007.10.007" @default.
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