There is considerable interest in developing non-peptidic, small-molecule alpha-helix mimetics to disrupt alpha-helix-mediated protein protein interactions. Herein, we report the design of a novel pyrrolopyrimidine-based scaffold for such alpha-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 alpha-helix mimetics.