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US 2026/0297130 A1Published application
Melanocortin receptor ligands modified with hydantoin
AssigneeIpsen Pharma S.A.S.
InventorsZheng Xin Dong, Daniel B. Deoliveira, Jeanne Mary Comstock
Life of this patent
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Abstract
The present invention relates to peptide ligands of the melanocortin receptors, in particular the melancortin-4 receptor, and as such, are useful in the treatment of disorders responsive to the activation of this receptor, such as obesity, diabetes mellitus and sexual dysfunction.
Claims50
A compound of formula
- wherein
- X is selected from the group consisting of —CH2—S—S—CH2—, —C(CH3)2—S—S—CH2—, —CH2—S—S—C(CH3)2—, —C(CH3)2—S—S—C(CH3)2—, —(CH2)2—S—S—CH2—, —CH2—S—S—(CH2)2—, —(CH2)2—S—S—(CH2)2—, —C(CH3)2—S—S—(CH2)2—, —(CH2)2—S—S—C(CH3)2, —(CH2)t—C(O)—NR8—(CH2)r— and —(CH2)r— NR8—C(O)—(CH2)t—;
- R1 and R2 each is, independently for each occurrence thereof, H, (C1-C10)alkyl or substituted (C1-C10)alkyl;
- R3 is —OH or —NH2;
- R4 and R5 each is, independently for each occurrence thereof, H, (C1-C10)alkyl or substituted (C1-C10)alkyl;
- X1 is
- A1 is His, 2-Pal, 3-Pal, 4-Pal, Taz, 2-Thi, 3-Thi, (X1, X2, X3, X4, X5)Phe or deleted;
- A2 is D-Bal, D-1-Nal, D-2-Nal, D-Phe or D-(X1, X2, X3, X4, X5)Phe;
- A3 is Arg, hArg, Dab, Dap, Lys or Orn;
- A4 is Bal, 1-Nal, 2-Nal, (X1, X2, X3, X4, X5)Phe or Trp;
- R6 and R7 each is, independently for each occurrence thereof, H, (C1-C10)alkyl, (C1-C10)heteroalkyl, aryl(C1-C5)alkyl, substituted (C1-C10)alkyl, substituted (C1-C10)heteroalkyl or substituted aryl(C1-C5)alkyl or R6 and R7 may be joined together form a cyclic moiety;
- R8 is H, (C1-C10)alkyl or substituted (C1-C10)alkyl;
- r is, independently for each occurrence thereof, 1, 2, 3, 4 or 5;
- and
- t is, independently for each occurrence thereof, 1 or 2;
- or
- a pharmaceutically acceptable salt thereof.
14 more elements
A compound of formula (II)
- wherein
- X1 is
- X2 is
- A1 is Asp, Cys, D-Cys, Dab, Dap, Glu, Lys, Orn, Pen or D-Pen;
- A2 is an L- or D-amino acid;
- A3 is His, 2-Pal, 3-Pal, 4-Pal, (X1, X2, X3, X4, X5)Phe, Taz, 2-Thi or 3-Thi;
- A4 is D-Bal, D-1-Nal, D-2-Nal, D-Phe or D-(X1, X2, X3, X4, X5)Phe;
- A5 is Arg, hArg, Dab, Dap, Lys or Orn;
- A6 is Bal, 1-Nal, 2-Nal, (X1, X2, X3, X4, X5)Phe or Trp;
- A7 is Asp, Cys, D-Cys, Dab, Dap, Glu, Lys, Orn, Pen or D-Pen;
- R1 is H, (C1-C10)alkyl or substituted (C1-C10)alkyl;
- R2 and R3 each is, independently, H, (C1-C10)alkyl, (C1-C10)heteroalkyl, aryl(C1-C5)alkyl, substituted (C1-C10)alkyl, substituted (C1-C10)heteroalkyl or substituted aryl(C1-C5)alkyl or R2 and R3 may be joined together form a cyclic moiety;
- R4 is CO2H or C(O)NH2;
- R5 and R6 each is, independently, H, (C1-C10)alkyl, (C1-C10)heteroalkyl, aryl(C1-C5)alkyl, substituted (C1-C10)alkyl, substituted (C1-C10)heteroalkyl or substituted aryl(C1-C5)alkyl or R5 and R6 may be joined together form a cyclic moiety;
- R7 and R8 each is, independently, H, (C1-C10)alkyl, (C1-C10)heteroalkyl, aryl(C1-C5)alkyl, substituted (C1-C10)alkyl, substituted (C1-C10)heteroalkyl or substituted aryl(C1-C5)alkyl;
- or R7 and R8 may be joined together form a cyclic moiety;
- R9 is H, (C1-C10)alkyl or substituted (C1-C10)alkyl;
- and
- n is, independently for each occurrence thereof, 1, 2, 3, 4, 5, 6 or 7;
- or
- a pharmaceutically acceptable salt thereof.
18 more elements
A compound of formula (III)
- wherein
- X is selected from the group consisting of —CH2—S—S—CH2—, —C(CH3)2—S—S—CH2—, —CH2—S—S—C(CH3)2—, —C(CH3)2—S—S—C(CH3)2—, —(CH2)2—S—S—CH2—, —CH2—S—S—(CH2)2, —(CH2)2—S—S—(CH2)2—, —C(CH3)2—S—S—(CH2)2—, —(CH2)2—S—S—C(CH3)2—, —(CH2)t—C(O)—NR8—(CH2)r— and —(CH2)r— NR8—C(O)—(CH2)t—;
- R1 and R5 each is, independently, H, (C1-C10)alkyl or substituted (C1-C10)alkyl;
- R2 and R3 each is, independently, H, (C1-C10)alkyl, (C1-C10)heteroalkyl, aryl(C1-C5)alkyl, substituted (C1-C10)alkyl, substituted (C1-C10)heteroalkyl or substituted aryl(C1-C5)alkyl or R2 and R3 may be joined together to form a ring;
- R4 is —OH or —NH2;
- R6 and R7 each is, independently, H, (C1-C10)alkyl or substituted (C1-C10)alkyl;
- A1 is an L- or D-amino acid or deleted;
- A2 is His, 2-Pal, 3-Pal, 4-Pal, (X1,X2,X3,X4,X5)Phe, Taz, 2-Thi or 3-Thi;
- A3 is D-Bal, D-1-Nal, D-2-Nal, D-Phe or D-(X1,X2,X3,X4,X5)Phe;
- A4 is Arg, hArg, Dab, Dap, Lys or Orn;
- A5 is Bal, 1-Nal, 2-Nal, (X1,X2,X3,X4,X5)Phe or Trp;
- r is, independently for each occurrence thereof, 1, 2, 3, 4 or 5;
- and
- t is, independently for each occurrence thereof, 1 or 2;
- or
- a pharmaceutically acceptable salt thereof.
13 more elements
A compound of the formula:
- or a pharmaceutically acceptable salt thereof.
Dependencies are inferred from the claim text.