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.
MeSH terms
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Animals
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Blood Glucose / metabolism
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Diabetes Mellitus, Type 2 / drug therapy*
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Dioxanes / chemical synthesis*
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Dioxanes / pharmacology*
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Disease Models, Animal
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Humans
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Hypoglycemic Agents / chemical synthesis
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Hypoglycemic Agents / pharmacology
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Hypolipidemic Agents / chemical synthesis
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Hypolipidemic Agents / pharmacology
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Lipoproteins / blood
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Magnetic Resonance Spectroscopy
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Mice
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Mice, Inbred Strains
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Molecular Structure
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Oxazoles / chemical synthesis*
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Oxazoles / pharmacology*
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PPAR alpha / agonists*
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Structure-Activity Relationship
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Triglycerides / blood
Substances
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2-methyl-c-5-(4-(5-methyl-2-phenyl-1,3-oxazol-4-yl)butyl)-1,3-dioxane-r-2-carboxylic acid
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Blood Glucose
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Dioxanes
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Hypoglycemic Agents
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Hypolipidemic Agents
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Lipoproteins
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Oxazoles
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PPAR alpha
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Triglycerides