Discovery of a new class of potent prolylcarboxypeptidase inhibitors derived from alanine

Bioorg Med Chem Lett. 2012 Feb 15;22(4):1774-8. doi: 10.1016/j.bmcl.2011.12.064. Epub 2011 Dec 24.

Abstract

Efforts to modify the central proline portion of lead compound 4 lead to the discovery of novel prolylcarboxypeptidase (PrCP) inhibitors. Especially, replacement with alanine afforded compound 19 displaying more potent human and mouse PrCP inhibitory activity than 4 and an overall comparable profile.

MeSH terms

  • Alanine / chemistry*
  • Alanine / pharmacology
  • Animals
  • Carboxypeptidases / antagonists & inhibitors*
  • Drug Discovery*
  • Enzyme Activation / drug effects
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Humans
  • Inhibitory Concentration 50
  • Mice
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • Enzyme Inhibitors
  • Carboxypeptidases
  • lysosomal Pro-X carboxypeptidase
  • Alanine