Synthesis and evaluation of a new series of peptide-based endothelin receptor antagonists.
Novel peptide-based endothelin (ET) receptor antagonists were designed and synthesized in our laboratory. BQ-485, HIM-CO-Leu-d-Trp-d-Trp-OH, was selected as the leading compound. The primary structures of these new tripeptides were ABO-CO-Leu-d-Trp-d-AA(X)-OH. The introduction of unnatural aromatic amino acids into these tripeptides was useful in the structure-activity relationship studies. Among the 20 tripeptides, 16 of them showed high activities against the contraction of rat aortic smooth muscles induced by ET-1.
Dong
J
J
Beijing Institute of Pharmacology and Toxicology, Beijing, China.
Han
H
H
Geng
B
B
Li
X
X
Gong
Z
Z
Liu
K
K
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D065128:Endothelin Receptor Antagonists; D006976:Hypertension, Pulmonary / Q000517:prevention & control; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis* / Q000494:pharmacology* / Q000627:therapeutic use; D051381:Rats; D017208:Rats, Wistar
D065128:Endothelin Receptor Antagonists; D009842:Oligopeptides