Cyclic polypeptides for the treatment of heart failure

A method of treating or preventing a disease or disorder responsive to the agonism of the APJ receptor, in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of a cyclic polypeptide having the following formula I (SEQ ID NO:

• 1):
• X1-R-X3-X4-L-S-X7-X8-X9-X10-X11-X12-X13 I
• wherein:
• X1 is the N-terminus of the polypeptide and is either absent, Q, A or pE or X1 is selected from C, c, hC, D-hC;
• wherein the side chain of C, c, hC or D-hC form a disulfide bond with the side chain of X7;
• X3 is P or X3 is selected from C, c, hC and D-hC;
• wherein the side chain of C, c, hC or D-hC forms a disulfide bond with the side chain of X7;
• X4 is R or X4 is selected from C, c, hC and D-hC;
• wherein the side chain of C, c, hC or D-hC forms a disulfide bond with the side chain of X7;
• wherein only one of X1, X3 and X4 is a sulfur contain amino-acid selected from C, c, hC and D-hC;
• X7 is C, c, hC or D-hC;
• and the side chain of X7 forms a disulfide bond with the side chain of C, c, hC or D-hC of either X1, X3 or X4;
• X8 is K or F;
• X9 is G, A, a or absent;
• X10 is P or absent;
• X11 is D-Nle, Nle, M or f;
• and
• X12 is absent or P, f, a, D-Nva or D-Abu;
• X13 is the C-terminus and is absent or is selected from (N-Me)F, F, f, a, y and Nal;
• wherein:
• Nle is L-norleucine;
• D-Nle is D-norleucine;
• D-hC is D-homocysteine
• hC is L-homocysteine;
• Nal is L-naphathaline;
• D-Nva is D-norvaline;
• D-Abu is D-2-aminobutyric acid;
• pE is L-pyroglutamic acid;
• or an amide, an ester or a salt of the polypeptide;
• or a polypeptide substantially equivalent
• thereto.