Discovery and optimization of a novel class of orally active nonpeptidic endothelin-A receptor antagonists.
A novel class of endothelin-A receptor ligands was discovered by high-throughput screening. Lead structure optimization led to highly potent antagonists which can be synthesized in a short sequence. The compounds are endothelin-A-selective, are orally available, and show a long duration of action.
Riechers
H
H
Hauptlaboratorium, BASF AG, Ludwigshafen, Germany.
Albrecht
H P
HP
Amberg
W
W
Baumann
E
E
Bernard
H
H
Böhm
H J
HJ
Klinge
D
D
Kling
A
A
Müller
S
S
Raschack
M
M
Unger
L
L
Walker
N
N
Wernet
W
W
D000284:Administration, Oral; D000818:Animals; D003619:Dansyl Compounds / Q000494:pharmacology; D003645:Death, Sudden; D015195:Drug Design; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000037:antagonists & inhibitors / Q000633:toxicity*; D006801:Humans; D008024:Ligands; D008958:Models, Molecular; D015394:Molecular Structure; D011743:Pyrimidines / Q000138:chemical synthesis* / Q000494:pharmacology; D051381:Rats; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin / Q000378:metabolism; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000494:pharmacology; D000096926:Benzenesulfonamides
D003619:Dansyl Compounds; D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D008024:Ligands; D011743:Pyrimidines; D044022:Receptor, Endothelin A; D017466:Receptors, Endothelin; D013449:Sulfonamides; C083751:Ro 46-2005; D000096926:Benzenesulfonamides; C085754:5-(dimethylamino)-N-(3,4-dimethyl-5-isoxazolyl)-1-naphthalenesulfonamide