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Novel pyrrolopyrimidine-based α-helix mimetics: cell-permeable inhibitors of protein−protein interactions.

Journal of the American Chemical Society 133(4):676 (2011) PMID 21171592 PMCID PMC3079198

There is considerable interest in developing non-peptidic, small-molecule α-helix mimetics to disrupt α-helix-mediated protein−protein interactions. Herein, we report the design of a novel pyrrolopyrimidine-based scaffold for such α-helix mimetics with increased conformational rigidity. We also developed a facile solid-phase synthetic route that is amenable to divergent synthesis of a large library. Using a fluorescence polarization-based assay, we identified cell-permeable, dual MDMX/MDM2 inhibitors, demonstrating that the designed molecules can act as α-helix mimetics.

DOI: 10.1021/ja108230s