Benzoxazinones as PPARγ Agonists. Part 1. SAR of Three Aromatic Regions.

Abstract A series of benzoxazinones was synthesized as PPARγ agonists. The compounds were obtained in seven steps, and SAR was developed by variations to the core shown below. The compounds were tested as functional agonists in the induction of the aP2 gene in preadipocytes, and the most potent compound in the series has an EC50=0.51 μM. The potency was further confirmed through a PPAR-Gal4 construct. Efficacy has been demonstrated in the db/db mouse model of hyperglycemia.