Disulfide bridged cyclic peptides containing a cgridri sequence useful in control of hypertension.

摘要

Disulfide bridged cyclic peptides are described which are preferably 13 to 20 amino acid residues in length and which include the endocyclic sequence cys-gly-arg-ile-asp-arg-ile. Peptides of this class are selective for and show picomolar-range affinity for the non-guanyl cyclase-coupled atrial peptide receptor. Affinity for this receptor is associated with potentiation of the mean arterial pressure response to atrial peptide and these peptides are therefore useful in control of hypertension. Peptides of most interest are of the formula <IMAGE> wherein X<1> is the peptidic fragment ser-ser; wherein X<2> is a peptidic fragment selected from gly-ser-gly-leu, gly-ala-gly-leu and gly-leu; wherein X<3> is the peptidic fragment asn-ser-phe-arg; wherein m is zero or one, n is one and r is one; and wherein A represents an amino terminus or its pharmaceutically-acceptable salt, and B represents a carboxyl terminus or its pharmaceutically-acceptable ester, amide or salt.