Identification of a new class of small molecule C5a receptor antagonists

Bioorg Med Chem Lett. 2010 Jan 15;20(2):662-4. doi: 10.1016/j.bmcl.2009.11.058. Epub 2009 Dec 7.


C5a is a terminal product of the complement cascade that activates and attracts inflammatory cells including granulocytes, mast cells and macrophages via a specific GPCR, the C5a receptor (C5aR). Inhibition of C5a/C5aR interaction has been shown to be efficacious in several animal models of autoimmune diseases, including RA, SLE and asthma. This account reports the discovery of a new class of C5aR antagonists through high-throughput screening. The lead compounds in this series are selective and block C5a binding, C5a-promoted calcium flux in human neutrophils with nanomolar potency.

MeSH terms

  • Animals
  • Cell Line
  • High-Throughput Screening Assays
  • Humans
  • Mice
  • Molecular Conformation
  • Neutrophils / immunology
  • Neutrophils / metabolism
  • Protein Binding
  • Receptor, Anaphylatoxin C5a / antagonists & inhibitors*
  • Receptor, Anaphylatoxin C5a / metabolism
  • Sulfonamides / chemical synthesis
  • Sulfonamides / chemistry*
  • Sulfonamides / pharmacology


  • Receptor, Anaphylatoxin C5a
  • Sulfonamides