Oligophenylenaminones as Scaffolds for α-Helix Mimicry

The design and synthesis of small molecule α-helix mimetics has been a productive field over the past decade. These compounds have performed well in a variety of biological systems as functional disruptors of α-helix-mediated protein–protein interactions. In our studies we have continued to develop novel, more biologically compatible scaffolds, which are often easier to assemble and capable of mimicking longer and/or more diverse helices. To this end, we have constructed a new series of i, i+4, i+7 α-helix mimics based on the enaminone scaffold. These molecules represent a step forward in the pursuit of idealized monofacial α-helix mimetics.