Bis-sulfonamides as endothelin receptor antagonists

Modification of the structure of bosentan 1, the first marketed endothelin receptor antagonist (Tracleer™), by introduction of a second sulfonamide function at the alkoxy side chain, led to bis-sulfonamides 2. This allowed to prepare dual ETA/ETB as well as ETB receptor selective antagonists, which could serve as tools to investigate the pharmacological consequences of selective ETB receptor blockade.