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 ET(A)/ET(B) as well as ET(B) receptor selective antagonists, which could serve as tools to investigate the pharmacological consequences of selective ET(B) receptor blockade.