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
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Animals
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Carboxylic Acids / chemical synthesis*
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Carboxylic Acids / pharmacokinetics*
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Diabetes Mellitus, Type 2 / drug therapy
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Dioxanes / chemical synthesis*
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Dioxanes / pharmacokinetics
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Humans
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Hypoglycemic Agents / chemical synthesis*
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Hypolipidemic Agents / chemical synthesis*
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Lipids / chemistry
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Mesylates / chemical synthesis*
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Mesylates / pharmacokinetics
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Mice
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Models, Chemical
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PPAR alpha / metabolism
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PPAR gamma / metabolism
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Peroxisome Proliferator-Activated Receptors / agonists
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Rats
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Rats, Wistar
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Transcriptional Activation
Substances
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5-(6-(4-methanesulfonyloxyphenyl)hexyl)-2-methyl-1,3-dioxane-2-carboxylic acid
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Carboxylic Acids
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Dioxanes
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Hypoglycemic Agents
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Hypolipidemic Agents
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Lipids
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Mesylates
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PPAR alpha
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PPAR gamma
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Peroxisome Proliferator-Activated Receptors