Cyclic peptide compositions for treatment of sexual dysfunction
View Patent ↗A cyclic peptide of the structural formula: or a pharmaceutically acceptable salt thereof, wherein R 1 , R 2 , R 3 , R 5 , R 6 , m, n and p are as defined. Further provided are compositions for treatment of sexual dysfunction in mammals, including male sexual dysfunction, such as erectile dysfunction, and female sexual dysfunction, by administration of a cyclic peptide including a C-terminus —OH group. Routes of administration include injection, oral, urethral, vaginal, nasal and mucosal administration.
1. 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 3 and R 5 are independently each an aromatic 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 with a terminal amino group, or an acylated C 1 to C 17 aliphatic linear or branched chain with a terminal amino group;
m is 1 to 4, and p is 1 to 5, provided that m+p is 2 to 7, and
n is 1 to 6.
2. The cyclic peptide of claim 1 wherein at least one of 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
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 2 is an amino acid side chain moiety comprising at least one 6-membered carbocyclic aromatic ring.
8. 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.
9. The cyclic peptide of claim 1 wherein R 1 is H.