Replacement of the triazolopiperazine ring of sitagliptin (DPP-4 IC(50)=18nM) with 3-(2,2,2-trifluoroethyl)-1,4-diazepan-2-one gave dipeptidyl peptidase IV (DPP-4) inhibitor 1 which is potent (DPP-4 IC(50)=2.6nM), selective, and efficacious in an oral glucose tolerance test in mice. It was selected for extensive preclinical development as a potential back-up candidate to sitagliptin.
        
Representative scheme of DPP4N_Peptidase_S9 structure and an image from PDBsum server
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Databases
PDB-Sum
2IIV Previously Class, Architecture, Topology and Homologous superfamily - PDB-Sum server
FSSP
2IIVFold classification based on Structure-Structure alignment of Proteins - FSSP server