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

Bioorg Med Chem Lett. 2005 Oct 1;15(19):4239-42. doi: 10.1016/j.bmcl.2005.06.075.

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-alpha (FAP) optimally preferred N-cycloheptyl whereas DPP7 tolerated even larger cycloalkyl rings. Gly alpha-carbon derivatization of N-cyclohexyl or N-(2-adamantyl) Gly-boro-Pro resulted in a significant decrease in potency against all the three DPPs.

MeSH terms

  • Adenosine Deaminase Inhibitors
  • Antigens, Neoplasm
  • Biomarkers, Tumor / antagonists & inhibitors
  • Boronic Acids
  • Dipeptides / chemical synthesis*
  • Dipeptides / pharmacology
  • Dipeptidyl Peptidase 4
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases / antagonists & inhibitors*
  • Endopeptidases
  • Gelatinases
  • Glycoproteins / antagonists & inhibitors
  • Humans
  • Immunologic Factors / chemical synthesis
  • Immunologic Factors / pharmacology
  • Inhibitory Concentration 50
  • Membrane Proteins
  • Serine Endopeptidases
  • Structure-Activity Relationship

Substances

  • Adenosine Deaminase Inhibitors
  • Antigens, Neoplasm
  • Biomarkers, Tumor
  • Boronic Acids
  • Dipeptides
  • Glycoproteins
  • Immunologic Factors
  • Membrane Proteins
  • Endopeptidases
  • Dipeptidyl-Peptidases and Tripeptidyl-Peptidases
  • dipeptidyl peptidase II
  • DPP4 protein, human
  • Dipeptidyl Peptidase 4
  • Serine Endopeptidases
  • fibroblast activation protein alpha
  • Gelatinases