BMS-196085: A potent and selective full agonist of the human β3 adrenergic receptor

A series of 4-hydroxy-3-methylsulfonanilido-1,2-diarylethylamines were prepared and evaluated for their human β3 adrenergic receptor agonist activity. SAR studies led to the identification of BMS-196085 (25), a potent β3 full agonist (Ki=21 nM, 95% activation) with partial agonist (45%) activity at the β1 receptor. Based on its desirable in vitro and in vivo properties, BMS-196085 was chosen for clinical evaluation.