Recent discovery and development of endothelin receptor antagonists

Endothelin (ET) receptor antagonists, in particular ETA selective or ETA/ETB balanced antagonists represents a new therapeutic area for serious diseases such as congestive heart failure (CHF) and pulmonary hypertension. Endothelin antagonists have profound effects on the pulmonary vasculature and the right heart whereas ACE inhibitors primarily affect the peripheral vessel and the left heart. Therefore, combination of endothelin antagonists and ACE inhibitors may be particularly useful in chronic heart failure. Pulmonary hypertension represents another unmet medical need where endothelin antagonists, especially orally-active compounds, show great promise. The importance of this field is evidenced by the number of compounds in clinical trials and by the number of patents filed in recent years. Between January 1997 and April 2000, there are 139 endothelin patents of which 128 are concerned with endothelin receptor antagonists and 11 with endothelin converting enzyme inhibitors. Of the 128 patents, 33 are about new chemical structures, 16 process, 4 formulation, 14 new use or combination therapy and 1 natural product. This article focuses on the 33 novel composition of matter patents in the area of endothelin receptor antagonists.