Amy Mae Bunker

1,3-DIARYL-2-CARBOXYINDOLES AS POTENT NON-PEPTIDE ENDOTHELIN ANTAGONISTS

Abstract Endothelin-1 is a potent vasoconstrictor that is thought to be involved in many human disease states. We have developed a series of indole non-peptide endothelin antagonists including PD 159110 ( 31 ), an ET A selective antagonist, and PD 159020 ( 37 ), a non-selective ET A /ET B antagonist. The discovery, synthesis, and structure-activity relationships of this series of compounds are described.

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

Abstract 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 ET A selective antagonist with an IC 50 of 2 nM. The discovery, synthesis and structure-activity relationships of this series of compounds are described.

Endothelin receptor antagonists: synthesis and structure–activity relationships of substituted benzothiazine-1,1-dioxides

The development of benzothiazine-1,1-dioxide derivatives as a new structural class of potent endothelin receptor antagonists is described. Structure-activity relationships (SAR) revealed that PD164800 (1) is a potent antagonist of the ETA receptor subtype.