Identification of a New Class of ET A Selective Endothelin Antagonists by Pharmacophore Directed Screening

Novel endothelin antagonists were identified through a "pharmacophore directed screening" strategy. The sulfanilamide antibacterial agent sulfisoxazole was found to be a good endothelin receptor antagonist (IC 50′s of 0.60 μM and 22 μM for the ET A and ET B receptors, respectively). The structurally similar sulfamethoxazole was found to be a weaker antagonist (IC 50 for ET A 16 μM and for ET B 230 μM). These compounds represent a new class of low molecular weight and ET A-selective non-peptide endothelin antagonists.