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

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.
Tomiyoshi Aoki 1,  Tetsuo Asaki,  Taisuke Hamamoto,  Yukiteru Sugiyama,  Shinji Ohmachi,  Kenji Kuwabara,  Kohji Murakami,  Makoto Todo
Affiliations

Affiliation

  • 1 Discovery Research Laboratories, Nippon Shinyaku Co., Ltd, 14 Nishinosho-Monguchi-Cho, Kisshoin, Minami-Ku, Kyoto 601-8550, Japan.
PMID: 18280733 DOI: 10.1016/j.bmcl.2008.01.086
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-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.

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