The successful launches of dipeptidyl peptidase IV (DPP IV) inhibitors as oral anti-diabetics warrant and spur the further quest for additional chemical entities in this promising class of therapeutics. Numerous pharmaceutical companies have pursued their proprietary candidates towards the clinic, resulting in a large body of published chemical structures associated with DPP IV. Herein, we report the discovery of a novel chemotype for DPP IV inhibition based on the C-(1-aryl-cyclohexyl)-methylamine scaffold and its optimization to compounds which selectively inhibit DPP IV at low-nM potency and exhibit an excellent oral pharmacokinetic profile in the rat.
        
Representative scheme of DPP4N_Peptidase_S9 structure and an image from PDBsum server
no Image
Databases
PDB-Sum
4N8E Previously Class, Architecture, Topology and Homologous superfamily - PDB-Sum server
FSSP
4N8EFold classification based on Structure-Structure alignment of Proteins - FSSP server