Design, synthesis, and evaluation of novel aryl-tetrahydropyridine PPARα/γ dual agonists

Aryl-tetrahydropyridine derivatives were prepared and their PPARα/γ dual agonistic activities were evaluated. Among them, compound (S)-5b was identified as a potent PPARα/γ dual agonist with an EC50 of 1.73 and 0.64 μM in hPPARα and γ, respectively. In diabetic (db/db) mice, compound (S)-5b showed good glucose lowering efficacy and favorable pharmacokinetic properties.

The synthesis of the potent PPARα/γ dual agonist (S)-5b (EC50 = 1.73/0.64 μM (α/γ)) is reported.Figure optionsDownload as PowerPoint slide