Endothelin receptor antagonists--an overview

In thirteen years since the appearance of Endothelin (ET) on the international scene, possibility of its involvement in a variety of diseases has attracted the attention of medicinal chemists in search of novel therapeutics for various cardiovascular diseases (CVDs). Discovery of pharmaceutical agents which either block the generation of ET from its precursor or antagonize its binding to cellular receptor, should not only provide means to assess the physiological role of ET, but lead to useful therapy for conditions associated with altered production or responsiveness to ET. In this review article, we have attempted to present in a classified format, the kaleidoscope of ET receptor antagonists that have emerged through structure activity relationship studies using the parent peptide as well as from screening of various compound libraries. By all indications, the variety and range of small molecules that are currently under investigation continues to open up newer opportunities and lures fresh groups of scientists into this research arena. Presently a number of these compounds are in the clinics, being evaluated for their beneficial effects in a range of human pathologies such as essential hypertension and chronic heart failure.