Endothelin receptor antagonists: an overview of their synthesis and structure-activity relationship.
Endothelins (ETs) are potent vasoconstrictor peptides and are associated with several disease states like pulmonary hypertension, systemic hypertension and heart failure. Endothelin-1 (ET-1) is the first member of the family and it has the receptor subtypes known as ETA and ETB. The receptors ETA and ETB are attractive new therapeutic targets for diseases associated with elevated ET-1 levels. Several studies have thus led to the discovery of selective ETA receptor antagonists as well as non-selective ETA/ETB antagonists. The preclinical and clinical studies have clearly established that these antagonists are effective in the treatment of essential hypertension, pulmonary hypertension, heart failure and atherosclerosis. The advances in this area have resulted in the FDA approval of the orally active dual antagonist Bosentan for pulmonary hypertension in 2001. This review highlights the synthesis and structure-activity of the endothelin receptor antagonists and covers the literature in this area up to 2001.
Iqbal
Javed
J
Dr. Reddy's Laboratories Ltd., Discovery Research, Discovery Chemistry, Bollaram Road, Miyapur, Hyderabad 500049, India. javediqbaldrf@hotmail.com
Sanghia
Rashmi
R
Das
Saibal Kumar
SK
D000595:Amino Acid Sequence; D000818:Animals; D015195:Drug Design; D065128:Endothelin Receptor Antagonists; D016232:Endothelins / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D008969:Molecular Sequence Data; D013329:Structure-Activity Relationship
D065128:Endothelin Receptor Antagonists; D016232:Endothelins