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.
Boss
Christoph
C
Drug Discovery Chemistry and Preclinical Research, Actelion Pharmaceuticals Ltd, Gewerbestrasse 16, CH-4123 Allschwil/BL, Switzerland. christoph.boss@actelion.com
Bolli
Martin H
MH
Weller
Thomas
T
Fischli
Walter
W
Clozel
Martine
M
D000818:Animals; D001011:Aorta / Q000187:drug effects / Q000502:physiology; D016466:CHO Cells; D006224:Cricetinae; D065128:Endothelin Receptor Antagonists; D006801:Humans; D020128:Inhibitory Concentration 50; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000502:physiology; D051381:Rats; D017466:Receptors, Endothelin / Q000378:metabolism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry* / Q000494:pharmacology*; D014661:Vasoconstriction / Q000187:drug effects
D065128:Endothelin Receptor Antagonists; D017466:Receptors, Endothelin; D013449:Sulfonamides