Synthesis and structure–activity relationship of N-alkyl Gly-boro-Pro inhibitors of DPP4, FAP, and DPP7

The structure–activity relationship of various N-alkyl Gly-boro-Pro derivatives against three dipeptidyl peptidases (DPPs) was studied. In a series of N-cycloalkyl analogs, DPP4 and fibroblast activation protein-α (FAP) optimally preferred N-cycloheptyl whereas DPP7 tolerated even larger cycloalkyl rings. Gly α-carbon derivatization of N-cyclohexyl or N-(2-adamantyl) Gly-boro-Pro resulted in a significant decrease in potency against all the three DPPs.

Graphical abstractThe structure-activity relationship of various N-alkyl Gly-boro-Pro derivatives against three dipeptidyl peptidases (DPP4, FAP, and DPP7) was explored.Figure optionsDownload full-size imageDownload as PowerPoint slide