1-benzyl-3-thioaryl-2-carboxyindoles as potent non-peptide endothelin antagonists

Endothelin-1 is a potent vasoconstrictor which is thought to be involved in many human disease states. We have developed a series of indole non-peptide endothelin antagonists which display nanomolar receptor affinity. The representative compound from this series is PD 159433 (22), an ETA selective antagonist with an IC50 of 2 nM. The discovery, synthesis and structure-activity relationships of this series of compounds are described.