Structure-activity relationships in a series of orally active γ-hydroxy butenolide endothelin antagonists

…, JT Repine, KA Berryman, BR Reisdorph…

Index: Patt, William C.; Edmunds, Jeremy J.; Repine, Joseph T.; Berryman, Kent A.; Reisdorph, Billy R.; Lee, Chet; Plummer, Mark S.; Shahripour, Aurash; Haleen, Stephen J.; Keiser, Joan A.; Flynn, Mike A.; Welch, Kathleen M.; Reynolds, Elwood E.; Rubin, Ron; Tobias, Brian; Hallak, Hussein; Doherty, Annette M. Journal of Medicinal Chemistry, 1997 , vol. 40, # 7 p. 1063 - 1074

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Citation Number: 49

Abstract

The design of potent and selective non-peptide antagonists of endothelin-1 (ET-1) and its related isopeptides are important tools defining the role of ET in human diseases. In this report we will describe the detailed structure-activity relationship (SAR) studies that led to the discovery of a potent series of butenolide ETA selective antagonists. Starting from a micromolar screening hit, PD012527, use of Topliss decision tree analysis led to the ...