Identification of nonpeptidic small-molecule inhibitors of interleukin-2

Abstract The identification, design, and synthesis of a series of novel sulfamide- and urea-based small-molecule antagonists of the protein–protein interaction IL-2/IL-2Rα are described. Installation of a furan carboxylic acid fragment onto a low-micromolar sulfamide resulted in a 23-fold improvement in activity, providing a sub-micromolar, nonpeptidic IL-2 inhibitor (IC 50  = 0.60 μM).