Substituted oxazole benzenesulfonamides as potent human beta(3) adrenergicreceptor agonists

As a part of our investigation into the development of orally bioavailable beta(3) adrenergic receptor agonists, we have identified a series of substi tuted oxazole derivatives that are potent beta(3) agonists with excellent s electivity against other beta receptors. Several of these compounds showed excellent oral bioavailability in dogs. One example, cyclopentylethyloxazol e 5f is a potent beta(3) agonist (EC50 = 14 nM, 84% activation) with 340-fo ld and 160-fold selectivity over beta(1) and beta(2) receptors, respectivel y, and has 38% oral bioavailability in dogs. (C) 2000 Elsevier Science Ltd. All rights reserved.