Structure-based design and synthesis of benzimidazole derivatives as dipeptidyl peptidase IV inhibitors

A novel series of non-covalent, benzimidazole-based inhibitors of DPP-4 has been developed from a small fragment hit using structure-based drug design. A highly versatile synthetic route was created for the development of SAR, which led to the discovery of potent and selective inhibitors with excellent pharmaceutical properties.

Graphical abstractA series of potent benzimidazole-based inhibitors of DPP-4 was designed and synthesized. Structural properties and biological activities are described.Figure optionsDownload full-size imageDownload as PowerPoint slide