Synthetic apelin mimetics for the treatment of heart failure

A polypeptide having Formula VI (SEQ ID NO:

• 81):
• or an amide, an ester or a salt of the polypeptide
• wherein:
• X1 is the N-terminus of the polypeptide and is either absent or is selected from pE, R, Isn, Q,
• A, K, and 5-amino-valeric acid;
• X2 is R, A, r, N-Me-R, K, H, hF, hK, F, E or Orn;
• X4 is R, A, r, N-Me-R, F, E;
• X5 is L, Cha, A, D-L, N-Me-L, K, D, 4-PhF or F;
• X8 is K, k, F, f, A, hF, N-Me-R, E or 4-amino-Isn;
• X9 is G, N-Me-G, A, D, L, R or Aib;
• X10 is P, A, p, 4-PhP or pipecolic acid,
• X11 is M, D-Nle, Nle, N-Me-Nle, M(O), A, F, Y, L, K, 3-PyA or Cha;
• and
• X13 is the C-terminus and is absent or is selected from F, f, N-Me-F, Nal, D-Nal, 3-Br-F, (S)-β-3-F, I, A, a, K, Dap, H and E;
• wherein:
• Nle is L-norleucine;
• hF is L-homophenylalanine;
• hK is L-lysine;
• Nal is L-naphathaline;
• Orn is ornithine;
• Aib is α-aminoisobutyric acid;
• Dab is (S)-diaminobutyric acid;
• Dap is (S)-2,3-diaminopropionic acid;
• M(O) is methionine sulfone;
• Cha is (S)-β-cyclohexylalanine;
• 4-amino-Isn is 4-aminopiperidine-4-carboxylic acid;
• Isn is isonipecotinoyl;
• pE is L-pyroglutamic acid;
• 3-PyA is 3-(3-pyridyl)-L-alanine;
• 4-PhF is 4-Phenyl-L-phenylalanine;
• wherein the N-terminus and the C-terminus optionally form a ring together with 1, 2, 3 or 4 glycine amino acids;
• and
• wherein the amino group in the side chain of K, Orn, Dab, Dap, hK or 4-amino-Isn is optionally linked to a lipophilic group via an amide bond.