(4-Piperidin-1-yl)phenyl Amides: Potent and Selective Human β₃ Agonists

Abstract

In search of potent and selective human β3 agonists as potential drugs for the treatment of human obesity and type II diabetes, a series of (4-piperidin-1-yl)phenyl amides was prepared and evaluated for their biological activity on the human β3-adrenergic receptor. The leucine derivative 26e and the reverse amide 33b were found to be the two most potent and selective compounds in this study. With EC50 values of 0.008 and 0.009 μM, respectively, at the β3 receptor, nearly completely abolished intrinsic activity at either the β1 or β2 receptor, and significant thermogenesis effects on human β3-adrenergic receptor transgenic mice, 26e and 33b are among the most potent and selective human β3 agonists known to date.