| 摘要 |
Melanocortin receptor-specific cyclic heptapeptides of the formula
Z-Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6-Xaa7-Y (II)
or a pharmaceutically acceptable salt thereof, where Z, Xaa1, Xaa2, Xaa3, Xaa4, Xaa5, Xaa6, Xaa7 and Y are as defined in the specification, compositions and formulations including the peptides of the foregoing formula, and methods of preventing, ameliorating or treating melanocortin receptor-mediated diseases, indications, conditions and syndromes. |
| 主权项 |
1. A cyclic heptapeptide of formula (II)
Z-Xaa1-Xaa2-Xaa3-Xaa4-Xaa5-Xaa6-Xaa7-Y (II)or a pharmaceutically acceptable salt thereof, wherein:
Z is H or an N-terminal group; Xaa1 is an amino acid with a side chain including at least one primary amine, guanidine or urea group; Xaa2 and Xaa7 are amino acids wherein the side chains thereof form a lactam-containing cyclic bridge; Xaa3 is Pro, optionally substituted with hydroxyl, halogen, sulfonamide, alkyl, —O-alkyl, aryl, alkyl-aryl, alkyl-O-aryl, alkyl-O-alkyl-aryl, or —O-aryl, or Xaa3 is an amino acid with a side chain including at least one primary amine, secondary amine, alkyl, cycloalkyl, cycloheteroalkyl, aryl, heteroaryl, ether, sulfide, or carboxyl; Xaa4 is an amino acid with a side chain including unsubstituted phenyl or naphthyl; Xaa5 is Pro or Xaa5 is an amino acid with a side chain including at least one primary amine, secondary amine, guanidine, urea, alkyl, cycloalkyl, cycloheteroalkyl, aryl, heteroaryl, or ether; Xaa6 is an amino acid with a side chain including at least one aryl or heteroaryl, optionally substituted with one or more ring substituents, and when one or more are present, are the same or different and independently hydroxyl, halogen, sulfonamide, alkyl, —O-alkyl, aryl, or —O-aryl; and Y is a C-terminal group; but excluding cyclic peptides wherein Z is Ac, Xaa1 is Arg, Xaa2 and Xaa7 together are Glu . . . Orn, Orn . . . Glu, or Asp . . . Lys, Xaa3 is Pro or Ser(Bzl), Xaa4 is D-Phe, Xaa5 is Arg, Xaa6 is Trp, and Y is —OH or —NH2. |
