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.

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