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

Bioorg Med Chem Lett. 2007 Mar 1;17(5):1438-42. doi: 10.1016/j.bmcl.2006.11.072. Epub 2006 Dec 1.

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.

MeSH terms

  • Adenosine Deaminase Inhibitors
  • Antigens, Neoplasm
  • Biomarkers, Tumor / antagonists & inhibitors
  • Boron Compounds / chemical synthesis*
  • Boron Compounds / pharmacology
  • Dipeptidyl Peptidase 4
  • Dipeptidyl-Peptidase IV Inhibitors
  • Endopeptidases
  • Gelatinases
  • Glycoproteins / antagonists & inhibitors
  • Membrane Proteins
  • Proline / chemistry*
  • Proline / pharmacology
  • Prolyl Oligopeptidases
  • Serine Endopeptidases / drug effects
  • Serine Proteinase Inhibitors / chemical synthesis*
  • Serine Proteinase Inhibitors / chemistry
  • Serine Proteinase Inhibitors / pharmacology*
  • Structure-Activity Relationship

Substances

  • Adenosine Deaminase Inhibitors
  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Boron Compounds
  • Dipeptidyl-Peptidase IV Inhibitors
  • Glycoproteins
  • Membrane Proteins
  • Serine Proteinase Inhibitors
  • Proline
  • Endopeptidases
  • DPP4 protein, human
  • Dipeptidyl Peptidase 4
  • Serine Endopeptidases
  • fibroblast activation protein alpha
  • PREPL protein, human
  • Prolyl Oligopeptidases
  • Gelatinases