ABSTRACT
In our search for new PPARα/γ agonists, we designed and synthesized a series of benzoylazole-based carboxylic acids. Compound 9 showed potent PPARγ partial agonistic activity with modest PPARα agonistic activity. The sodium salt of 9 (9Na) demonstrated potent efficacy in lowering both blood glucose and lipids in an animal model without causing significant body weight gain, a well-known side effect associated with PPARγ full agonists.
Subject(s)
Azoles/chemical synthesis , Azoles/pharmacology , PPAR alpha/agonists , PPAR gamma/agonists , Animals , Azoles/chemistry , Humans , Hypoglycemic Agents/chemistry , Hypoglycemic Agents/pharmacology , Hypolipidemic Agents/chemistry , Hypolipidemic Agents/pharmacology , Mice , Models, Animal , Models, MolecularABSTRACT
Starting with a subtle blood glucose-lowering effect of a TGF-ß inhibitor, we designed and synthesized a series of benzoylpyrrole-based carboxylic acids as PPARs activators. Among these compounds, 10sNa exhibited favorable blood glucose-lowering effect without body weight gain. We assume that the beneficial effect of 10sNa is attributed to not only its compound PPARα agonistic activity but also its PPARγ partial agonistic activity.
