Abstract
Medicinal chemistry efforts on optimization of the endothelin receptor antagonistic natural products toward highly potent and selective ETA, ETB or ETA/B dual receptor antagonists are summarized. In order to get adequate biological tools for elucidating physiological and/or pathophysiological roles of endothelin as well as to identify highly potent antagonists possessing appropriate profiles, liquid phase and solid phase peptide synthesis, and their modification have been carried out. During these efforts, we have realized physiological roles of endothelin and its receptors, and have confirmed drug discovery values of its receptor antagonists as clinical drugs to modulate various kinds of disease.
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