Conformational properties of O-alkylated benzamides

In this article, we report the synthesis, solid-state and solution-state conformational studies of O-alkylated aromatic benzamides based on two scaffolds. Intramolecular hydrogen bonding provides conformational pre-organization and side chains can interact with each other within a molecule. In the solid-state three-dimensional arrangement, the molecules further interact with each other through noncovalent interactions. Given, the demonstrated potential of this class of scaffolds to act as helix mimetics for the inhibition of protein-protein interactions (PPIs), these results provide key insight for future inhibitor design. (C) 2011 Elsevier Ltd. All rights reserved.