Synthesis and structure-activity relationship of N-acyl-Gly-, N-acyl-Sar-and N-blocked-boroPro inhibitors of FAP, DPP4, and POP

Abstract The structure–activity relationship of various N -acyl-Gly-, N -acyl-Sar-, and N-blocked-boroPro derivatives against three prolyl peptidases was explored. Several N -acyl-Gly- and N-blocked-boroPro compounds showed low nanomolar inhibitory activity against fibroblast activation protein (FAP) and prolyl oligopeptidase (POP) and selectivity against dipeptidyl peptidase-4 (DPP4). N -Acyl-Sar-boroPro analogs retained selectivity against DPP4 and potent POP inhibitory activity but displayed decreased FAP inhibitory activity.