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    Bioorg Med Chem Lett. 2008 Mar 15;18(6):2128-32. Epub 2008 Jan 30.

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

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

    Discovery Research Laboratories, Nippon Shinyaku Co., Ltd, 14 Nishinosho-Monguchi-Cho, Kisshoin, Minami-Ku, Kyoto 601-8550, Japan.

    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-carboxylic 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.

    PMID: 18280733 [PubMed - indexed for MEDLINE]

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