Revisiting glitazars: Thiophene substituted oxazole containing α-ethoxy phenylpropanoic acid derivatives as highly potent PPARα/γ dual agonists devoid of adverse effects in rodents

In an effort to develop safe and efficacious compounds for the treatment of metabolic disorders, novel thiophene substituted oxazole containing α-alkoxy-phenylpropanoic acid derivatives are designed as highly potent PPARα/γ dual agonists. These compounds were found to be efficacious at picomolar concentrations. Lead compound 18d has emerged as very potent PPARα/γ dual agonist demonstrating potent antidiabetic and lipid lowering activity at a very low dose and did not exhibit any significant signs of toxicity in rodents.

Design and synthesis of a novel thiophene substituted oxazole derivatives are reported and their PPARα/γ agonistic activity has been evaluated. Lead compound 18d has demonstrated potent antidiabetic and lipid lowering activity devoid of treatment related adverse effects and eventually emerged as very potent PPARα/γ dual agonist.Figure optionsDownload as PowerPoint slide