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).
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Humans
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Inhibitory Concentration 50
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Interleukin-2 / antagonists & inhibitors*
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Interleukin-2 / metabolism
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Models, Molecular
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Protein Binding / drug effects
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Receptors, Interleukin-2 / metabolism
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Structure-Activity Relationship
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Sulfonic Acids / chemistry
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Sulfonic Acids / pharmacology
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Urea / chemistry
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Urea / pharmacology
Substances
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Interleukin-2
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Receptors, Interleukin-2
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Sulfonic Acids
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Urea
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sulfamic acid