Discovery of a highly orally bioavailable c-5-[6-(4-Methanesulfonyloxyphenyl)hexyl]-2-methyl-1,3-dioxane-r-2-carboxylic acid as a potent hypoglycemic and hypolipidemic agent

Bioorg Med Chem Lett. 2008 Oct 15;18(20):5586-90. doi: 10.1016/j.bmcl.2008.08.112. Epub 2008 Sep 3.

Abstract

A series of novel 1,3-dioxane-2-carboxylic acid derivatives containing alkyl chain tether and substituted phenyl group as a lipophilic tail have been prepared as agonists of PPARalpha and gamma. c-5-[6-(4-Methanesulfonyloxyphenyl)hexyl]-2-methyl-1,3-dioxane-r-2-carboxylic acid 13c exhibited potent hypoglycemic and lipid lowering activity with high oral bioavailability in animal models.

MeSH terms

  • Animals
  • Carboxylic Acids / chemical synthesis*
  • Carboxylic Acids / pharmacokinetics*
  • Diabetes Mellitus, Type 2 / drug therapy
  • Dioxanes / chemical synthesis*
  • Dioxanes / pharmacokinetics
  • Humans
  • Hypoglycemic Agents / chemical synthesis*
  • Hypolipidemic Agents / chemical synthesis*
  • Lipids / chemistry
  • Mesylates / chemical synthesis*
  • Mesylates / pharmacokinetics
  • Mice
  • Models, Chemical
  • PPAR alpha / metabolism
  • PPAR gamma / metabolism
  • Peroxisome Proliferator-Activated Receptors / agonists
  • Rats
  • Rats, Wistar
  • Transcriptional Activation

Substances

  • 5-(6-(4-methanesulfonyloxyphenyl)hexyl)-2-methyl-1,3-dioxane-2-carboxylic acid
  • Carboxylic Acids
  • Dioxanes
  • Hypoglycemic Agents
  • Hypolipidemic Agents
  • Lipids
  • Mesylates
  • PPAR alpha
  • PPAR gamma
  • Peroxisome Proliferator-Activated Receptors