Endothelin Receptor Antagonists: Structures, Synthesis, Selectivity and Therapeutic Applications

摘要

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