Selective endothelin A receptor ligands. 1. Discovery and structure-activity of 2, 4-disubstituted benzoic acid derivatives

…, RA Lewis, PM Lockey, C McCarthy, IM McLay…

Index: Astles; Brown; Handscombe; Harper; Harris; Lewis; Lockey; McCarthy; McLay; Porter; Roach; Smith; Walsh European Journal of Medicinal Chemistry, 1997 , vol. 32, # 5 p. 409 - 423

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Citation Number: 10

Abstract

This paper describes the discovery of a new non-peptide endothelin A (ETA) selective ligand, 2, 4-dibenzyloxybenzoic acid 3, which inhibits the binding of [125I] ET-1 to ETA receptors with an IC50 of 9 μM (ET-1= endothelin-1). Optimisation of 3 resulted in compound 52 which had an IC50 of 1 μM. One of the analogues of 3, compound 15, was examined in a functional assay and shown to antagonise ET-1-induced contraction of rat aorta. The ...