Angiotensin II is a peptide hormone known best as a vasoconstrictor with central roles in chronic hypertension, heart failure, and stroke.1 It is an octapeptide typically generated by the removal of two residues from angiotensin I by angiotensin-converting enzyme (ACE).2 Angiotensin II is a ligand for at least two distinct receptors, AT1 and AT2, each evoking distinct signaling pathways and physiological responses.1,3 The development of antagonists for specific angiotensin II receptor subtypes represents a valuable alternative to ACE inhibitors.4
1.Burnier, M.Angiotensin II type 1 receptor blockersCirculation103(6)904-912(2001) 2.Redelinghuys, P., Nchinda, A.T., and Sturrock, E.D.Development of domain-selective angiotensin I-converting enzyme inhibitorsAnn. N. Y. Acad. Sci.1056160-175(2005) 3.Bosnyak, S., Jones, E.S., Christopoulos, A., et al.Relative affinity of angiotensin peptides and novel ligands at AT1 and AT2 receptorsClin. Sci. (Lond.)121(7)297-303(2011) 4.Wexler, R.R., Greenlee, W.J., Irvin, J.D., et al.Nonpeptide angiotensin II receptor antagonists: The next generation in antihypertensive therapyJ. Med. Chem.39(3)625-656(2014)