Design and synthesis of potent, orally active, inhibitors of carboxypeptidase U (TAFIa)

Bioorg Med Chem. 2004 Mar 1;12(5):1151-75. doi: 10.1016/j.bmc.2003.12.039.

Abstract

A series of 3-mercapto-propionic acid derivatives that function as reversible inhibitors of carboxypeptidase U have been prepared. We present a successful design strategy using cyclic, low basicity guanidine mimetics resulting in potent, selective and bioavailable inhibitors of carboxypeptidase U (TAFIa).

MeSH terms

  • 3-Mercaptopropionic Acid / chemical synthesis*
  • 3-Mercaptopropionic Acid / pharmacology
  • Administration, Oral
  • Biological Availability
  • Carboxypeptidase B2 / antagonists & inhibitors*
  • Drug Design
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / pharmacology
  • Guanidine
  • Humans
  • Inhibitory Concentration 50
  • Molecular Mimicry
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • 3-Mercaptopropionic Acid
  • Carboxypeptidase B2
  • Guanidine