Melanocortin receptor ligands
The present invention is directed to compounds according to formula, (R 2 R 3 )-A 1 - c (A 2 -A 3 -A 4 -A 5 -A 6 -A 7 -A 8 -A 9 )-A 10 -R 1 , and pharmaceutically-acceptable salts thereof that act as ligands for one or more of the melanocortin receptors, to methods of using such compounds to treat mammals and to pharmaceutical compositions comprising said compounds.
1. A compound selected from the group consisting of:
D-Phe-c(Cys-His-D-(Et)Tyr-Arg-Trp-β-Ala-D-Cys)-Thr-NH 2 (SEQ ID NO:24);
D-Phe-c(Cys-His-D-Phe-Arg-Trp-β-Ala-D-Cys)-Thr-NH 2 (SEQ ID NO:3);
D-Phe-c(Cys-His-D-Phe-Arg-Trp-Gaba-D-Cys)-Thr-NH 2 (SEQ ID NO:3);
D-Phe-c(Cys-His-D-Phe-hArg-Trp-β-Ala-D-Cys)-Thr-NH 2 (SEQ ID NO:23);
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-NH 2 (SEQ ID NO:24);
D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-NH 2 (SEQ ID NO:26);
D-Phe-c(Cys-His-D-Phe-Arg-Bip-β-Ala-D-Cys)-Thr-NH 2 (SEQ ID NO:25);
D-Phe-c(Cys-His-D-Phe-hArg-Bip-β-Ala-D-Cys)-Thr-NH 2 (SEQ ID NO:26); and
Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH 2 (SEQ ID NO:11);
or a pharmaceutically acceptable salt thereof.
2. A compound according to claim 1 , wherein the compound is D-Phe-c(Cys-His-D-Phe-Arg-Bip-β-Ala-D-Cys)-Thr-NH 2 (SEQ ID NO:25) or a pharmaceutically acceptable salt thereof.
3. A compound according to claim 1 , wherein the compound is D-Phe-c(Cys-His-D-Phe-hArg-Bip-β-Ala-D-Cys)-Thr-NH 2 (SEQ ID NO: 26) or a pharmaceutically acceptable salt thereof.
4. A compound according to claim 1 , wherein the compound is D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Bip-β-Ala-D-Cys)-Thr-NH 2 (SEQ ID NO:26) or a pharmaceutically acceptable salt thereof.
5. A compound according to claim 1 , wherein the compound is D-Phe-c(Cys-His-D-(Et)Tyr-hArg-Trp-β-Ala-D-Cys)-Thr-NH 2 (SEQ ID NO:24) or a pharmaceutically acceptable salt thereof.
6. A compound according to claim 1 , wherein the compound is Ac-hCha-c(Asp-His-D-Phe-Arg-Trp-Gaba-Lys)-NH 2 ; (SEQ ID NO:11) or a pharmaceutically acceptable salt thereof.
7. A pharmaceutical composition comprising a therapeutically effective amount of a compound of claim 1 , or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier or diluent.
8. A method of treating a metabolic disease or medical condition accompanied by weight gain, comprising administering to a subject in need thereof a therapeutically effective amount of compound of claim 1 .
9. The method of claim 8 , wherein the disease or condition is selected from obesity, feeding disorders, Prader-Willi Syndrome, or diabetes.