Identification of a new class of ETA 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 (IC50's of 0.60 microM and 22 microM for the ETA and ETB receptors, respectively). The structurally similar sulfamethoxazole was found to be a weaker antagonist (IC50 for ETA 16 microM and for ETB 230 microM). These compounds represent a new class of low molecular weight and ETA-selective non-peptide endothelin antagonists.
Chan
M F
MF
Department of Medicinal Chemistry, ImmunoPharmaceutics, Inc., San Diego, CA 92127.
Okun
I
I
Stavros
F L
FL
Hwang
E
E
Wolff
M E
ME
Balaji
V N
VN
D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects; D015195:Drug Design; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000378:metabolism; D006801:Humans; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D013444:Sulfisoxazole / Q000494:pharmacology
D065128:Endothelin Receptor Antagonists; D016232:Endothelins; D044022:Receptor, Endothelin A; D044023:Receptor, Endothelin B; D013444:Sulfisoxazole