Isosteric ramatroban analogs: selective and potent CRTH-2 antagonists

Bioorg Med Chem Lett. 2005 Mar 15;15(6):1749-53. doi: 10.1016/j.bmcl.2004.12.055.

Abstract

The chemoattractant receptor-homologous molecule expressed on T(H)2 cells (CRTH-2), also found on eosinophils and basophils, is a prostaglandin D2 receptor involved in the recruitment of these cell types during an inflammatory response. In this report, we describe the synthesis and optimization of a ramatroban isostere that is a selective and potent antagonist of CRTH-2 which may be useful in the treatment of certain diseases.

MeSH terms

  • Anti-Asthmatic Agents / chemistry
  • Anti-Asthmatic Agents / pharmacology
  • Carbazoles / chemistry*
  • Carbazoles / pharmacology*
  • Isomerism
  • Models, Chemical
  • Molecular Conformation
  • Molecular Structure
  • Receptors, Immunologic / antagonists & inhibitors*
  • Receptors, Prostaglandin / antagonists & inhibitors*
  • Structure-Activity Relationship
  • Sulfonamides / chemistry*
  • Sulfonamides / pharmacology*

Substances

  • Anti-Asthmatic Agents
  • Carbazoles
  • Receptors, Immunologic
  • Receptors, Prostaglandin
  • Sulfonamides
  • ramatroban
  • prostaglandin D2 receptor