Recently discovered sulfonamide-, acyl sulfonamide- and carboxylic acid-based endothelin antagonists.
Endothelins (ET-1, 2 and 3) are 21-residue peptides with two disulfide bridges and a highly conserved carboxy terminal. ET-1, the most significant isoform, is a potent vasoconstrictor and mitogen that exerts its biological effects through binding to its two G protein-coupled receptors: ET(A) and ET(B). ET(A) receptors are expressed on vascular smooth muscle cells and mediate vasoconstrictive and proliferative responses to ET-1. ET(B) receptors are mainly located on endothelial cells where they clear ET-1 from circulation and mediate vasodilation via the release of nitric oxide. ET-1 has been associated with a variety of serious diseases such as pulmonary hypertension, heart failure, prostate cancer and renal dysfunction.
Wu
Chengde
C
Texas Biotechnology Corporation, Suite 1920, 7000 Fannin, Houston, TX 77030 USA. cwu@tbc.com
Holland
George W
GW
Brock
Tommy A
TA
Dixon
Richard A F
RA
D000818:Animals; D002264:Carboxylic Acids / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D065128:Endothelin Receptor Antagonists; D006801:Humans; D013449:Sulfonamides / Q000737:chemistry* / Q000494:pharmacology / Q000627:therapeutic use; D014652:Vascular Diseases / Q000188:drug therapy
D002264:Carboxylic Acids; D065128:Endothelin Receptor Antagonists; D013449:Sulfonamides