Cyclic peptide compositions for treatment of sexual dysfunction

1. A synthetic cyclic peptide of the structural formula I:

or a pharmaceutically acceptable salt thereof,

wherein:

R 2 is H, a C 1 to C 6 aliphatic linear or branched chain, or an aromatic amino acid side chain moiety comprising at least one 6-membered carbocyclic aromatic ring;

R 3 and R 5 are independently each an aromatic amino acid side chain moiety;

R 4 is a C 1 to C 6 linear or branched chain amino acid side chain or a neutral hydrogen bonding or positively charged amino acid side chain moiety;

R 6 is in each instance H;

R 7 is H, an aliphatic L- or D-amino acid, an N-acylated L- or D-amino acid, a linear or branched C 1 to C 17 alkyl, aryl, heteroaryl, alkene, alkenyl, or aralkyl chain, a C 1 to C 17 aliphatic linear or branched chain, optionally with a terminal amino group, or an acylated C 1 to C 17 aliphatic linear or branched chain, optionally with a terminal amino group; and

m is 1 to 4, and p is 1 to 5, provided that m+p is 2 to 7.

2. The cyclic peptide of claim 1 wherein R 3 and R 5 are aromatic amino acid side chain moieties of a natural or synthetic L- or D-amino acid.

3. The cyclic peptide of claim 1 wherein at least one of R 3 and R 5 are selected from the following:

4. The cyclic peptide of claim 1 wherein m is 1 and p is 4.

5. The cyclic peptide of claim 1 wherein

is

H 2 N—,

wherein:

R 9 is a C 1 to C 6 aliphatic linear or branched chain or an aromatic amino acid side chain moiety; and

q is 1 to 16.

6. The cyclic peptide of claim 1 wherein R 3 is

wherein each of R 8 and R 8 ′ is independently H or a halogen, alkyl or aryl group, on the proviso that at least one of R 8 and R 8 ′ is not H.

7. The cyclic peptide of claim 1 wherein R 5 is an amino acid side chain moiety comprising at least one 6-membered carbocyclic aromatic ring but not comprising a ring with a nitrogen ring member.

8. The cyclic peptide of claim 1 wherein R 1 is H.

9. The cyclic peptide of claim 1 wherein R 4 is a neutral hydrogen bonding or positively charged amino acid side chain moiety.

10. The cyclic peptide of claim 9 wherein the neutral hydrogen bonding or positively charged amino acid side chain moiety is an aliphatic or aromatic amino acid side chain moiety is obtained from a natural or synthetic L- or D-amino acid.

11. The cyclic peptide of claim 10 wherein the neutral hydrogen bonding or positively charged amino acid side chain moiety comprises at least one nitrogen-containing group.

12. The cyclic peptide of claim 11 wherein the at least one nitrogen-containing group is an amide, imide, amine, guanidine, urea, urethane, or nitrile.

13. The cyclic peptide of claim 11 wherein the at least one nitrogen-containing group is selected from the following:

14. The cyclic peptide of claim 1 wherein R 4 is a neutral aliphatic amino acid side chain moiety.

15. The cyclic peptide of claim 14 wherein the neutral aliphatic amino acid side chain moiety is a hydrogen donor and/or acceptor.

16. The cyclic peptide of claim 14 wherein the neutral aliphatic amino acid side chain moiety is selected from the following:

17. A synthetic cyclic peptide of the structural formula:

or a pharmaceutically acceptable salt thereof,

wherein:

R 2 is H, a C 1 to C 6 aliphatic linear or branched chain, or an aromatic amino acid side chain moiety;

R 4 is a C 1 to C 6 linear or branched chain amino acid side chain or a neutral hydrogen bonding or positively charged amino acid side chain moiety;

R 5 is an aromatic amino acid side chain moiety;

R 6 is H;

R 7 is H, an aliphatic L- or D-amino acid, an N-acylated L- or D-amino acid, a linear or branched C 1 to C 17 alkyl, aryl, heteroaryl, alkene, alkenyl, or aralkyl chain, a C 1 to C 17 aliphatic linear or branched chain with a terminal amino group, or an acylated C 1 to C 17 aliphatic linear or branched chain with a terminal amino group;

R 8 and R 8 ′ are independently each H or a halogen, alkyl or aryl group, on the proviso that at least one of R 8 and R 8 ′ is not H; and

m is 1 to 4, and p is 1 to 5, provided that m+p is 2 to 7.

18. The cyclic peptide of claim 17 wherein R 5 is an aromatic amino acid side chain moiety of a natural or synthetic L- or D-amino acid.

19. The cyclic peptide of claim 17 wherein R 5 is selected from the following:

20. The cyclic peptide of claim 17 wherein m is 1 and p is 4.

21. The cyclic peptide of claim 17 wherein

is

H 2 N—,

wherein:

R 9 is a C 1 to C 6 aliphatic linear or branched chain or an aromatic amino acid side chain moiety; and

q is 1 to 16.

22. The cyclic peptide of claim 17 wherein R 1 is H.

23. The cyclic peptide of claim 17 wherein R 4 is a neutral hydrogen bonding or positively charged amino acid side chain moiety.

24. The cyclic peptide of claim 23 wherein the neutral hydrogen bonding or positively charged amino acid side chain moiety is an aliphatic or aromatic amino acid side chain moiety is obtained from a natural or synthetic L- or D-amino acid.

25. The cyclic peptide of claim 24 wherein the neutral hydrogen bonding or positively charged amino acid side chain moiety comprises at least one nitrogen-containing group.

26. The cyclic peptide of claim 25 wherein the at least one nitrogen-containing group is an amide, imide, amine, guanidine, urea, urethane, or nitrile.

27. The cyclic peptide of claim 25 wherein the at least one nitrogen-containing group is selected from the following:

28. The cyclic peptide of claim 17 wherein R 4 is a neutral aliphatic amino acid side chain moiety.

29. The cyclic peptide of claim 28 wherein the neutral aliphatic amino acid side chain moiety is a hydrogen donor and/or acceptor.

30. The cyclic peptide of claim 28 wherein the neutral aliphatic amino acid side chain moiety is selected from the following: