Design, Synthesis and Evaluation of Peroxisome Proliferator-Activated Receptor α/βDual Agonists for the Treatment of Type 2 Diabetes

The design, synthesis and evaluation of several dual PPARα/γ agonists with three different heterocycles, viz. pyrazolo[4,3-d]pyrimidin-7-one, quinazolin-4-one and benzo[e][1,3]oxazine-4-one for the treatment of type 2 diabetes and associated dyslipidemia are described. Among them, compound 5cb was found to possess a potent dual PPARα/β agonist property. It significantly reversed diabetic hyperglycemia while improving overall lipid homeostasis in preclinical animal models. Keywords: PPAR, Diabetes, Synthesis, Ethyl 3-(4-aminophenyl)-2-ethoxypropionate, Dyslipidemia and Plasma glucose