Substituted oxazole benzenesulfonamides as potent human β3 adrenergic receptor agonists

Abstract As a part of our investigation into the development of orally bioavailable β 3 adrenergic receptor agonists, we have identified a series of substituted oxazole derivatives that are potent β 3 agonists with excellent selectivity against other β receptors. Several of these compounds showed excellent oral bioavailability in dogs. One example, cyclopentylethyloxazole 5f is a potent β 3 agonist (EC 50 =14 nM, 84% activation) with 340-fold and 160-fold selectivity over β 1 and β 2 receptors, respectively, and has 38% oral bioavailability in dogs.