MELANOCORTIN RECEPTOR LIGANDS MODIFIED WITH HYDANTOIN

摘要

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.

主权项

1. A compound of formulawherein
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)tC(O)—NR8—(CH2), and —(CH2)r— NR8—C(O)—(CH2); 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; ora pharmaceutically acceptable salt thereof.