التفاصيل البيبلوغرافية
| العنوان: |
MELANOCORTIN ANALOGS WITH ANTIMICROBIAL ACTIVITY |
| Document Number: |
20120015873 |
| تاريخ النشر: |
January 19, 2012 |
| Appl. No: |
13/144858 |
| Application Filed: |
January 19, 2009 |
| مستخلص: |
The present invention finds application in the therapeutic fields. In particular, it concerns new synthetic melanocortin peptides having improved antimicrobial activity. |
| Inventors: |
Catania, Anna (Milano, IT); Bonino, Ferruccio (Milano, IT); Grieco, Paolo (Milano, IT); Novellino, Ettore (Milano, IT) |
| Claim: |
1. Peptides having the general formula (1): W-A1-A2-A3-A4-X-A5-A6-A7-Y (1) wherein A1 is selected in the group comprising: either D- or L-isomer of hystidine or any hystidine analogues, such as, methylhystidine or 6-carboxy-1,2,3,4-tetrahydro-imidazopyridin or any other hystidine metabolic precursors or a charged amino acids, such as ornitine or lysine and any natural amino acids; A2 is selected in the group comprising: D(2)Nal or Phe, D-Phe, Nal(1), D-Nal(1), Nal(2), Tyr, D-Tyr and any other aromatic amino acids, both D- and L-isomer, or A2 is Isoleucine; A3 is selected in the group comprising: Arg, Lys, Orn, Pro, Phe,(p-amino)Phe or it may be Dap, Dab, Dpm; A4 is selected in the group comprising: either D- or L-isomer of Trp, (α-Me)Trp, Trp(Me), Trp(CHO), Arg, D-Nal(1) and D-Nal(2); A5 is selected in the group comprising: either D- or L-isomer of Lysine, Ornitine or it may be Dap or Dab; A6 is selected in the group comprising: either D- or L-isomer of Phe, Pro, Nal(1), Nal(2) or any other aromatic amino acids; A7 is selected in the group comprising: D- or L-isomer of Val, Thr, Leu, Ile, tert-Leu, Nle or it may be Abu; wherein W may be H or any suitable carboxy protecting groups, such as a satured or unsatured straight or branched C1-C8 acyl group or alkanoyl; or W may be any D- or L-amino acids, such as, Ala, Nle, Gly or the Gly-Gly dimer or the Ala-Ala dimer; or W may be H-Glu-Thr-Pro-Asp, H-Thr-Pro-Asp, —H-Pro-Asp or H-Asp, or W may be H-Phe-Phe-His; wherein Y is any suitable protecting groups, such as an hydroxyl group (—OH) or an acyl group; and wherein X is selected in the group comprising non-conventional amino acids or X is one or more natural aromatic amino acids or a single bond or Gly or the Gly-Gly dimer or the Ala-Ala dimer. |
| Claim: |
2. Peptides according to claim 1, wherein A1 is His and A2, A3, A4, A5, A6, A7, W, Y and X have the same meanings as in claim 1. |
| Claim: |
3. Peptides according to claim 1, wherein A2 is D(2)Nal and A1, A3, A4, A5, A6, A7, W, Y and X have the same meanings as in claim 1. |
| Claim: |
4. Peptides according to claim 1, wherein A3 is Arg and A1, A2, A4, A5, A6, A7, W, Y and X have the same meanings as in claim 1. |
| Claim: |
5. Peptides according to claim 1, wherein A4 is L-Trp and A1, A2, A3, A5, A6, A7, W, Y and X have the same meanings as in claim 1. |
| Claim: |
6. Peptides according to claim 1, wherein A5 is Lys and A1, A2, A3, A4, A6, A7, W, Y and X have the same meanings as in claim 1. |
| Claim: |
7. Peptides according to claim 1, wherein A6 is Phe and A1, A2, A3, A4, A5, A7, W, Y and X have the same meanings as in claim 1. |
| Claim: |
8. Peptides according to claim 1, wherein A7 is Val and A1, A2, A3, A4, A5, A6, W, Y and X have the same meanings as in claim 1. |
| Claim: |
9. Peptides according to claim 1 having the general formula (1a): W-His-D(2)Nal-Arg-Trp-X-Lys-Phe-Val-Y (1a) wherein W, Y and X have the same meanings of claim 1. |
| Claim: |
10. Peptides according to claim 9, having the following formula: [table included] |
| Claim: |
11. Peptides according to claim 1, having the formula (1b): W-A1-A2-A3-A4-X-A5-A6-A7-Y (1b) wherein W is H-Phe-Phe-His; Y is a amino terminal group; A1 is His; A2 is Ile, Phe or (D)2-Nal; A3 is Arg or Phe; A4 is Arg, Trp or Gly; A5 is Lys; X is Gly or a single bond; A6 is Pro or Phe; and A7 is Val. |
| Claim: |
12. Peptides according to claim 11, having the following formula: [table included] |
| Claim: |
13-17. (canceled) |
| Claim: |
18. A pharmaceutical preparation comprising one or more of the peptides of claim 1. |
| Claim: |
19. The pharmaceutical preparation of claim 18 further comprising one or more active principle selected from the group comprising antibacterials, antifungals, antiviruses, antiparasitics agents. |
| Claim: |
20. The pharmaceutical preparation of claim 19, wherein said antifungal agents are selected in the group comprising clotrimazole, nystatin, fluconazole, ketoconazole, amphotericin B, caspofungin, voriconazole. |
| Claim: |
21. The pharmaceutical preparation of claim 18, further comprising excipients and additives selected in the group comprising diluent, solvents, bulking agents, fillers, reological modifier, stabilizers, binders, lubricants, disintegrant, preservatives, pH adjusting agents, buffers, antioxidant, chelating agents, plasticizer, polymers, emulsifiers, edulcorants, flavoring agents; alone or in combination thereof. |
| Claim: |
22. The pharmaceutical preparation of claim 18 for oral, rectal, nasal, topical, vaginal or parenteral administration. |
| Claim: |
23. The pharmaceutical preparation of claim 18, in the form of hard or soft capsules, tables, powders or granules, solutions syrups or suspensions in aqueous or non-aqueous liquids, edible foams or whips, oil-in-water or water-in-oil liquid emulsions, ointments, creams, suspensions, lotions, powders, solutions, pastes, gels, sprays, aerosols or oils, sprays or drops, pessaries, tampons, creams, gels, pastes, foams; aqueous or non-aqueous sterile injectable solutions or suspensions. |
| Claim: |
24. A method for the treatment of a patient affected by microorganisms, comprising the step of administering to said patient an effective amount of a peptide according to claim 1. |
| Claim: |
25. The method of claim 24, wherein said microorganism is selected from Candida microorganisms. |
| Claim: |
26. The method of claim 25, wherein said Candida is selected from Candida albicans, Candida glabrata and Candida krusei. |
| Claim: |
27. The method of claim 24, wherein said peptide is active against Candida microorganisms. |
| Claim: |
28. The method of claim 24, wherein said microorganism is selected from Staphylococcus aureus and Pseudomonas aeruginosa. |
| Current U.S. Class: |
514/27 |
| Current International Class: |
61; 61; 61; 07 |
| رقم الانضمام: |
edspap.20120015873 |
| قاعدة البيانات: |
USPTO Patent Applications |