Bioorganic & Medicinal Chemistry Letters 2005-02-15

Identification of nonpeptidic small-molecule inhibitors of interleukin-2.

Nathan D Waal, Wenjin Yang, Johan D Oslob, Michelle R Arkin, Jennifer Hyde, Wanli Lu, Robert S McDowell, Chul H Yu, Brian C Raimundo

Index: Bioorg. Med. Chem. Lett. 15(4) , 983-7, (2005)

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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-2Ralpha 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 microM).