Peptidomimetic C5a receptor antagonists with hydrophobic substitutions at the C-terminus: increased receptor specificity and in vivo activity

Bioorg Med Chem Lett. 2006 Oct 1;16(19):5088-92. doi: 10.1016/j.bmcl.2006.07.036. Epub 2006 Jul 28.


A new class of peptidomimetic C5a receptor antagonists characterized by C-terminal amino acids with hydrophobic side chains is presented. Systematic optimization of the first hits led to JPE1375 (36), which was intensively characterized in vitro and in vivo. Compound 36 exhibits high microsomal stability and receptor specificity and is highly active in an immune complex mediated peritonitis model (reverse passive Arthus reaction) in mice.

MeSH terms

  • Animals
  • Antigen-Antibody Complex / adverse effects
  • Disease Models, Animal
  • Hydrophobic and Hydrophilic Interactions
  • Inhibitory Concentration 50
  • Mice
  • Molecular Mimicry
  • Oligopeptides / chemistry*
  • Oligopeptides / pharmacology*
  • Peritonitis / chemically induced
  • Peritonitis / drug therapy*
  • Receptor, Anaphylatoxin C5a / antagonists & inhibitors*
  • Structure-Activity Relationship
  • Substrate Specificity


  • Antigen-Antibody Complex
  • Oligopeptides
  • Receptor, Anaphylatoxin C5a