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

Abstract 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.