Melanocortin receptor-specific peptides
Melanocortin receptor-specific cyclic peptides of the formula where R 1 , R 2 , R 3 , R 4 , R 5 , R 6 , R 7 , R 8 , R 9 , R 10 and z 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.
1. A cyclic peptide having the structure of formula (III):
or a pharmaceutically acceptable salt thereof,
wherein
R 10 is
—(CH 2 ) x —C(═O)—NH—(CH 2 ) y —,
—(CH 2 ) x —NH—C(═O)—(CH 2 ) y —,
—(CH 2 ) x —C(═O)—(CH 2 ) z —C(═O)—(CH 2 ) y —,
—(CH 2 ) x —C(═O)—NH—C(═O)—(CH 2 ) y —, or
—(CH 2 ) x —NH—C(═O)—NH—(CH 2 ) y —:
x is 1 to 5;
y is 1 to 5; and
z is in each instance independently 1 to 5.
2. The cyclic peptide of claim 1 wherein R 10 is —(CH 2 ) x —NH—C(═O)—(CH 2 ) y — where x is 3 and y is 2.
3. The cyclic peptide of claim 1 which is a peptide of the structure:
4. A pharmaceutical composition comprising a cyclic peptide of claim 1 and a pharmaceutically acceptable carrier.
5. A method for treatment of a melanocortin receptor-mediated disease, indication, condition or syndrome in a human or nonhuman mammal, comprising the step of administering the pharmaceutical composition of claim 4 .
6. A method for treating a condition responsive to changes in melanocortin receptor function in a human or non-human mammal, comprising the step of administering the pharmaceutical composition of claim 4 .
7. The cyclic peptide according to claim 3 , which is an acetate salt.
8. The cyclic peptide according to claim 3 , which is a trifluoroacetate salt.
9. A cyclic peptide which is
Ac-Arg-cyclo(Om-Asn-D-Phe-Arg-Trp-Glu)-NH 2 .
10. A pharmaceutical composition comprising the cyclic peptide according to claim 9 and a pharmaceutically acceptable carrier.
11. A method for treatment of a melanocortin receptor-mediated disease, indication, condition or syndrome in a human or non-human mammal, comprising the step of administering the pharmaceutical composition of claim 9 .
12. A method for treating a condition responsive to changes in melanocortin receptor function in a human or non-human mammal, comprising the step of administering the pharmaceutical composition of claim 9 .