Ligands of melanocortin receptors

A compound according to formula (I)

• (R2R3)-B1-A1-c(A2-A3-A4-A5-A6-A7-A8-A9)-A10-A11-A12-A13-B2-B3-R1
• wherein:
• B1 is a peptide moiety which contains 5, 6, 7, 8, 9, 10, 11, 12, 13, 14 or 15 amino acids, wherein at least 5 amino acids are independently selected from the group consisting of L-Arg, D-Arg, L-hArg and D-hArg, or B1 is optionally deleted;
• A1 is Acc, HN—(CH2)m—C(O), L- or D-amino acid or deleted;
• A2 is Cys, D-Cys, hCys, D-hCys, Pen, D-Pen, Asp or Glu;
• A3 is Gly, Glu, Ala, β-Ala, Gaba, Aib, D-amino acid or deleted;
• A4 is His, 2-Pal, 3-Pal, 4-Pal, Taz, 2-Thi, 3-Thi or (X1,X2,X3,X4,X5)Phe;
• A5 is D-Phe, D-1-Nal, D-2-Nal, D-Trp, D-Bal, D-(X1,X2,X3,X4,X5)Phe, D-(Et)Tyr, D-Dip, D-Bip or D-Bpa;
• A6 is Arg, hArg, Dab, Dap, Lys, Orn or HN—CH((CH2)n—N(R4R5))—C(O);
• A7 is Trp, 1-Nal, 2-Nal, Bal, Bip, Dip, Bpa, D-Trp, D-1-Nal, D-2-Nal, D-Bal, D-Bip, D-Dip or D-Bpa;
• A8 is Gly, D-Ala, Acc, Ala, β-Ala, Gaba, Apn, Ahx, Aha, HN—(CH2)s—C(O) or deleted;
• A9 is Cys, D-Cys, hCys, D-hCys, Pen, D-Pen, Dab, Dap, Orn or Lys;
• A10 is Acc, HN—(CH2)t—C(O), Pro, hPro, 3-Hyp, 4-Hyp, Thr, an L- or D-amino acid or deleted;
• A11 is Pro, hPro, 3-Hyp, 4-Hyp or deleted;
• A12 is Lys, Dab, Dap, Arg, hArg or deleted;
• A13 is Asp, Glu or deleted;
• B2 is a peptide moiety containing 3, 4, or 5 amino acids or deleted,
• B3 is a peptide moiety which contains 5, 6, 7, 8, 9, 10, 11, 12, 13, 14, or 15 amino acids wherein at least 5 amino acids are independently selected from the group consisting of L-Arg, D-Arg, L-hArg and D-hArg, or is deleted;
• R1 is —OH or —NH2;
• R2 and R3 each is, independently for each occurrence, selected from the group consisting of H, (C1-C30)alkyl, (C1-C30)heteroalkyl, (C1-C30)acyl, (C2-C30)alkenyl, (C2-C30)alkynyl, aryl(C1-C30)alkyl, aryl(C1-C30)acyl, substituted (C1-C30)alkyl, substituted (C1-C30)heteroalkyl, substituted (C1-C30)acyl, substituted (C2-C30)alkenyl, substituted (C2-C30)alkynyl, substituted aryl(C1-C30)alkyl and substituted aryl(C1-C30)acyl;
• R4 and R5 each is, independently for each occurrence, H, (C1-C40)alkyl, (C1-C40)heteroalkyl, (C1-C40)acyl, (C2-C40)alkenyl, (C2-C40)alkynyl, aryl(C1-C40)alkyl, aryl(C1-C40)acyl, substituted (C1-C40)alkyl, substituted (C1-C40)heteroalkyl, substituted (C1-C40)acyl, substituted (C2-C40)alkenyl, substituted (C2-C40)alkynyl, substituted aryl(C1-C40)alkyl, substituted aryl(C1-C40)acyl, (C1-C40)alkylsulfonyl or —C(NH)—NH2;
• n is, independently for each occurrence, 1, 2, 3, 4 or 5;
• m is, independently for each occurrence, 1, 2, 3, 4, 5, 6 or 7;
• s is, independently for each occurrence, 1, 2, 3, 4, 5, 6 or 7;
• t is, independently for each occurrence, 1, 2, 3, 4, 5, 6 or 7;
• X1, X2, X3, X4 and X5 each is, independently for each occurrence, H, F, Cl, Br, I, (C1-10)alkyl, substituted (C1-10)alkyl, (C2-10)alkenyl, substituted (C2-10)alkenyl, (C2-10)alkynyl, substituted (C2-10)alkynyl, aryl, substituted aryl, OH, NH2, NO2 or CN;
• provided that:
• (I) when R4 is (C1-C40)acyl, aryl(C1-C40)acyl, substituted (C1-C40)acyl, substituted aryl(C1-C40)acyl, (C1-C40)alkylsulfonyl or —C(NH)—NH2, then R5 is H, (C1-C40)alkyl, (C1-C40)heteroalkyl, (C2-C40)alkenyl, (C2-C40)alkynyl, aryl(C1-C40)alkyl, substituted (C1-C40)alkyl, substituted (C1-C40)heteroalkyl, substituted (C2-C40)alkenyl, substituted (C2-C40)alkynyl or substituted aryl(C1-C40)alkyl;
• (II) when R2 is (C1-C30)acyl, aryl(C1-C30)acyl, substituted (C1-C30)acyl or substituted aryl(C1-C30)acyl, then R3 is H, (C1-C30)alkyl, (C1-C30)heteroalkyl, (C2-C30)alkenyl, (C2-C30)alkynyl, aryl(C1-C30)alkyl, substituted (C1-C30)alkyl, substituted (C1-C30)heteroalkyl, substituted (C2-C30)alkenyl, substituted (C2-C30)alkynyl or substituted aryl(C1-C30)alkyl;
• (III) neither B1 nor B2 contains one or more of the following amino acid sequences:
• Arg-(Lys)2-(Arg)2-Gln-(Arg)3 (SEQ ID NO:1), Tyr-Ala-Arg-Lys-Ala-(Arg)2-Gln-Ala-(Arg)2 (SEQ ID NO:2), Tyr-Ala-Arg-(Ala)2-(Arg)2-(Ala)2-(Arg)2 (SEQ ID NO:3), Tyr-Ala-(Arg)9 (SEQ ID NO:4), Tyr-(Ala)3-(Arg)7 (SEQ ID NO:5), Tyr-Ala-Arg-Ala-Pro-(Arg)2-Ala-(Arg)3 (SEQ ID NO:6) or Tyr-Ala-Arg-Ala-Pro-(Arg)2-Pro-(Arg)2 (SEQ ID NO:7);
• (IV) either B1 or B2 or both must be present in said compound;
• (V) when A2 is Cys, D-Cys, hCys, D-hCys, Pen or D-Pen, then A9 is Cys, D-Cys, hCys, D-hCys, Pen or D-Pen;
• and
• (VI) when A2 is Asp or Glu, then A9 is Dab, Dap, Orn or Lys;
• or a pharmaceutically acceptable salt thereof.