Discovery and optimization of a novel class of orally active nonpeptidic endothelin-A receptor antagonists

H Riechers; H P Albrecht; W Amberg; E Baumann; H Bernard; H J Böhm; D Klinge; A Kling; S Müller; M Raschack; L Unger; N Walker; W Wernet

doi:10.1021/jm960274q

Discovery and optimization of a novel class of orally active nonpeptidic endothelin-A receptor antagonists

J Med Chem. 1996 May 24;39(11):2123-8. doi: 10.1021/jm960274q.

Authors

H Riechers¹, H P Albrecht, W Amberg, E Baumann, H Bernard, H J Böhm, D Klinge, A Kling, S Müller, M Raschack, L Unger, N Walker, W Wernet

Affiliation

¹ Hauptlaboratorium, BASF AG, Ludwigshafen, Germany.

PMID: 8667356
DOI: 10.1021/jm960274q

Abstract

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.

MeSH terms

Administration, Oral
Animals
Dansyl Compounds / pharmacology
Death, Sudden
Drug Design
Endothelin Receptor Antagonists*
Endothelins / antagonists & inhibitors
Endothelins / toxicity*
Humans
Ligands
Models, Molecular
Molecular Structure
Pyrimidines / chemical synthesis*
Pyrimidines / pharmacology
Rats
Receptor, Endothelin A
Receptors, Endothelin / metabolism
Structure-Activity Relationship
Sulfonamides / pharmacology

Substances

Dansyl Compounds
Endothelin Receptor Antagonists
Endothelins
Ligands
Pyrimidines
Receptor, Endothelin A
Receptors, Endothelin
Sulfonamides
Ro 46-2005
5-(dimethylamino)-N-(3,4-dimethyl-5-isoxazolyl)-1-naphthalenesulfonamide