Endothelin receptor antagonists: structures, synthesis, selectivity and therapeutic applications

Curr Med Chem. 2002 Feb;9(3):349-83. doi: 10.2174/0929867023371139.


Endothelin (ET) was discovered in 1988 and is the most potent vasoconstrictive peptide known to date. It exists in three isoforms (ET-1 to ET-3) and acts on two endothelin receptor subtypes, the endothelin-A (ET(A))-receptor and the endothelin-B (ET(B))-receptor. Endothelin receptor antagonists are novel therapeutics in clinical development for different cardiovascular, cerebrovascular, and renal diseases. Several different structural classes of endothelin receptor antagonists have been discovered within the last decade, starting from peptidic- and peptidomimetic structures to small organic molecules suitable as therapeutics for oral administration. Focussing on the small organic molecules, the different structural classes of ET-receptor antagonists are described with respect to synthesis, structure-activity-relationships, receptor-subtype-selectivity profile, and where possible, intended therapeutic indications.

Publication types

  • Review

MeSH terms

  • Drug Design*
  • Drugs, Investigational / chemical synthesis*
  • Drugs, Investigational / chemistry*
  • Drugs, Investigational / therapeutic use
  • Endothelin Receptor Antagonists*
  • Humans
  • Peptides / chemical synthesis
  • Peptides / chemistry
  • Peptides / therapeutic use
  • Structure-Activity Relationship


  • Drugs, Investigational
  • Endothelin Receptor Antagonists
  • Peptides