Peptides having pharmacological activity for treating disorders associated with altered cell migration, such as cancer

1. Peptides, in salt form or non-salt form, with the general formula L 1 -X 1 -X 2 -X 3 -X 4 , wherein:

L 1 is acyl, Glu, Gln, said Glu and Gln being optionally N-acylated or N-alkylated and/or Cα-alkylated, Pro, hydroxy-Pro, Azt, Pip, pGlu, said pGlu being optionally N-acylated and/or Cα-alkylated, Aib, Ac3c, Ac4c, Ac5c or Ac6c, said Aib, Ac3c, Ac4c, Ac5c or Ac6c being optionally N-acylated or N-alkylated;

X 1 and X 3 , which are equal or different, optionally N-alkylated and/or Cα-alkylated, are selected from Arg, Orn, Lys, and phenylalanine substituted in the meta or para positions with an amine or guanidine group;

X 2 is chosen from among Glu, Lys, said Glu and Lys being optionally N-alkylated and/or Cα-alkylated, Aib, Ac3c, Ac4c, Ac5c and Ac6c, said Aib, Ac3c, Ac4c, Ac5c and Ac6c being optionally N-alkylated;

X 4 is chosen from among Phe, h-Phe, Tyr, Trp, 1-Nal, 2-Nal, h-1-Nal, h-2-Nal, Cha, Chg and Phg, said Phe, h-Phe, Tyr, Trp, 1-Nal, 2-Nal, h-1-Nal, h-2-Nal, Cha, Chg and Phg being optionally amidated and/or Cα-alkylated,

with the proviso that when X 1 is Arg, X 2 is Glu, X 3 is Lys and X 4 is Tyr, L 1 cannot be Pro.

2. Peptides as claimed in claim 1 , wherein the acyl, or N acylating, N-alkylating, or Cα-alkylating groups contain 1 to 9 carbon atoms, and amidating C-terminal groups contain 0 to 14 carbon atoms.

3. Peptides as claimed in claim 1 , wherein the acyl or N-alkylating groups contain 1 or 2 carbon atoms, and amidating C-terminal groups contains 0 to 5 carbon atoms.

4. Pharmaceutical compositions comprising one of the peptides claimed in claim 1 , in association with suitable vehicles or excipients.

5. A method for the prevention or treatment of disorders associated with altered cell migration comprising administering an effective amount of a peptide of claim 1 to a human in need thereof.

6. Method as claimed in claim 5 , wherein said effective amount is from 0.1 μg to 1 g per dose.

7. Method as claimed in claim 5 , wherein said effective amount is between 0.1 mg and 100 mg per dose.

8. Method as claimed in claim 5 for the prevention or treatment of local or metastatic invasion by malignant tumors.

9. Method as claimed in claim 5 , for the prevention or treatment of disorders associated with neo-angiogenesis.

10. Method as claimed in claim 5 , for the prevention or treatment of disorders supported by cell migration and associated with chronic inflammation.

11. Method as claimed in claim 5 , for the prevention or treatment of diseases associated with herpes virus infection.

12. Method as claimed in claim 9 , wherein said disorders comprise retinal vasculopathies, retinopathies, macular degeneration and edema, or Kaposi's sarcoma.

13. Method as claimed in claim 10 , wherein said disorders comprise autoimmune diseases, rheumatoid arthritis, psoriasis or chronic granulomatous disorders.

14. Peptides as claimed in claim 1 , optionally in salt form, with the sequence: Ac-Arg-Glu-Arg-Phe-NH 2 SEQ ID NO. 66; pGlu-Arg-Glu-Arg-Tyr-OH SEQ ID NO. 67; Glu-Arg-Glu-Arg-Phe-NH 2 SEQ ID NO. 1; Ac-Arg-Glu-Arg-Tyr-NH 2 SEQ ID NO. 2; Ac-Arg-Glu-Arg-Trp-NH 2 SEQ ID NO. 3; Ac-Arg-Glu-N(Me)Arg-Phe-NH 2 SEQ ID NO. 4;

Ac-Arg-Glu-N(Me)Arg-Tyr-NH 2 SEQ ID NO. 5; Ac-Arg-Glu-N(Me)Arg-Trp-NH 2 SEQ ID NO.6; pGlu-Arg-Glu-N(Me)Arg-Phe-NH 2 SEQ ID NO. 7; pGlu-Arg-Glu-N(Me)Arg-Tyr-NH 2 SEQ ID NO. 8; pGlu-Arg-Glu-N(Me)Arg-Trp-NH 2 SEQ ID NO. 9; pGlu-Arg-Glu-Arg-Phe-NH 2 SEQ ID NO. 10; pGlu-Arg-Glu-Arg-Tyr-NH 2 SEQ ID NO. 11; pGlu-Arg-Glu-Arg-Trp-NH 2 SEQ ID NO. 12; Ac-Arg-Aib-Arg-Phe-NH 2 SEQ ID NO. 13; Ac-Arg-Aib-Arg-Tyr-NH 2 SEQ ID NO. 14;

Ac-Arg-Aib-Arg-Trp-NH 2 SEQ ID NO. 15; Ac-Aib -Arg-Aib-Arg-Phe-NH 2 SEQ ID NO. 16;

Ac-Arg-Aib-N(Me)Arg-Phe-NH 2 SEQ ID NO. 17; Ac-Arg-Aib-N(Me)Arg-Tyr-NH 2 SEQ ID NO. 18; Ac-Arg-Aib-N(Me)Arg-Trp-NH 2 SEQ ID NO. 19;pGlu-Arg-Aib-N(Me)Arg-Phe-NH 2 SEQ ID NO. 20; Glu-Arg-Aib-N(Me)Arg-Tyr-NH 2 SEQ ID NO. 21; pGlu-Arg-Aib-N(Me)Arg-Trp-NH 2 SEQ ID NO. 22; pGlu-Arg-Aib-Arg-Phe-NH 2 SEQ ID NO. 23; pGlu-Arg-Aib-Arg-Tyr-NH 2 SEQ ID NO. 24; pGlu-Arg-Aib-Arg-Trp-NH 2 SEQ ID NO. 25; Ac-Arg-Ac5c-Arg-Phe-NH 2 SEQ ID NO. 26; Ac-Arg-Ac5c-Arg-Tyr-NH 2 SEQ ID NO. 27; Ac-Arg-Ac5c-Arg-Trp-NH 2 SEQ ID NO. 28; Ac-Arg-Ac5c-N(Me)Arg-Phe-NH 2 SEQ ID NO. 29; Ac-Arg-Ac5c-N(Me)Arg- Tyr-NH 2 SEQ ID NO. 30; Ac-Arg-Ac5c-N(Me)Arg-Trp-NH 2 SEQ ID NO. 31; pGlu-Arg-Ac5c-N (Me)Arg-Phe-NH 2 SEQ ID NO. 32; pGlu-Arg-Ac5c-N(Me)Arg-Tyr-NH 2 SEQ ID NO. 33;

pGlu-Arg-Ac5c-N(Me)Arg-Trp-NH 2 SEQ ID NO. 34; pGlu-Arg-Ac5c-Arg-Phe-NH 2 SEQ ID NO. 35; pGlu-Arg-Ac5c-Arg-Tyr-NH 2 SEQ ID NO. 36; pGlu-Arg-Ac5c-Arg-Trp-NH 2 SEQ ID NO. 37; Ac-Arg-Glu-Arg-Phe-OH SEQ ID NO. 38; Ac-Arg-Glu-Arg-Tyr-OH SEQ ID NO. 39;

Ac-Arg-Glu-Arg-Trp-OH SEQ ID NO. 40; Ac-Arg-Glu-N(Me)Arg-Tyr-OH SEQ ID NO. 41;

pGlu-Arg-Glu-N(Me)Arg-Phe-OH SEQ ID NO. 42; pGlu-Arg-Glu-Arg-Trp-OH SEQ ID NO. 43; Ac-Arg-Aib-Arg-Phe-OH SEQ ID NO. 44; Ac-Arg-Aib-N(Me)Arg-Phe-OH SEQ ID NO. 45; pGlu-Arg-Aib-N(Me)Arg-Tyr-OH SEQ ID NO. 46; pGlu-Arg-Aib-Arg-Trp-OH SEQ ID NO. 47; Ac-Arg-Ac5c-Arg-Phe-OH SEQ ID NO. 48; Ac-Arg-Ac5c-N(Me)Arg-Tyr-OH SEQ ID NO. 49; pGlu-Arg-Ac5c-N(Me)Arg-Trp-OH SEQ ID NO. 50; pGlu-Arg-Ac5c-Arg-Trp-OH SEQ ID NO. 51; Ac—N(Me)Arg-Aib-Arg-Phe-NH 2 SEQ ID NO. 52; Ac—N(Me)Arg-Aib-N (Me)Arg-Phe-NH 2 SEQ ID NO. 53; Ac-Arg-Aib-N(Me)Arg-Phe-NH 2 SEQ ID NO. 54; Ac-Arg-Aib-Arg-α(Me)Phe-NH 2 SEQ ID NO. 55; Ac—N(Me)Arg-Aib-Arg-α(Me)Phe-NH 2 SEQ ID NO. 56; Ac—N(Me)Arg-Aib-N(Me)Arg-α(Me)Phe-NH 2 SEQ ID NO. 57; Ac-Arg-Aib-N Me)Arg-α(Me)Phe-NH 2 SEQ ID NO. 58; Ac-Aib-N(Me)Arg-Aib-Arg-Phe-NH 2 SEQ ID NO. 59; Ac-Aib-N(Me)Arg-Aib-N(Me)Arg-Phe-NH 2 SEQ ID NO. 60; Ac-Aib-Arg-Aib-N(Me)Arg-Phe-NH 2 SEQ ID NO. 61; Ac-Aib-Arg-Aib-Arg-α(Me)Phe-NH 2 SEQ ID NO. 62; Ac-Aib-N (Me)Arg-Aib-Arg-α(Me)Phe-NH 2 SEQ ID NO. 63; Ac-Aib-N(Me)Arg-Aib-N(Me)Arg-α(Me)Phe-NH 2 SEQ ID NO. 64; or Ac-Aib-Arg-Aib-N(Me)Arg-α(Me)Phe-NH 2 SEQ ID NO. 65.