Synthetic peptide amide dimers

A synthetic peptide amide dimer having the formula:

• or a stereoisomer, mixture of stereoisomers, pharmaceutically acceptable salt, hydrate, acid salt hydrate, or N-oxide thereof,
• wherein
• each Xaa1 is independently selected from the group consisting of (A)(A′)D-Phe, (A)(A′)(α-Me)D-Phe, D-Tyr, D-Tic, D-tert-leucine, D-neopentylglycine, D-phenylglycine, D-homophenylalanine, and β-(E)D-Ala, wherein each (A) and each (A′) are phenyl ring substituents independently selected from the group consisting of —H, —F, —Cl, —NO2, —CH3, —CF3, —CN, —CONH2, and wherein each (E) is independently selected from the group consisting of cyclobutyl, cyclopentyl, cyclohexyl, pyridyl, thienyl and thiazolyl;
• each Xaa2 is independently selected from the group consisting of (A)(A′)D-Phe, (A)(A′)(α-Me)D-Phe, D-1NaI, D-2NaI, D-Tyr, (E)D-Ala, and D-Trp;
• each Xaa3 is independently selected from the group consisting of D-Nle, D-Phe, (E)D-Ala, D-Leu, (α-Me)D-Leu, D-Hle, D-Val, and D-Met;
• each Xaa4 is independently selected from the group consisting of (B)2D-Arg, (B)2D-Nar, (B)2D-Har, ζ-Dap, ε-(B)D-Lys, ε-(B)2-D-Lys, D-Amf, amidino-D-Amf, γ-(B)2D-Dbu, δ-(B)2α-(B′)D-Orn, D-2-amino-3(4-piperidyl)propionic acid, D-2-amino-3(2-aminopyrrolidyl)propionic acid, D-α-amino-β-amidino-propionic acid, α-amino-4-piperidineacetic acid, cis-α,4-diaminocyclohexane acetic acid, trans-α,4-diaminocyclohexaneacetic acid, cis-α-amino-4-methyl-aminocyclo-hexane acetic acid, trans-α-amino-4-methylaminocyclohexane acetic acid, α-amino-1-amidino-4-piperidineacetic acid, cis-α-amino-4-guanidino-cyclohexane acetic acid, and trans-α-amino-4-guanidinocyclohexane acetic acid, wherein each (B) is independently selected from the group consisting of —H and C1-C4 alkyl, and (B′) is —H or (α-Me), and p is zero or 1;
• q is zero or 1;
• r is zero or 1;
• s is zero or 1;
• p and t are each independently zero or 1, provided that at least one of q, r, s and t is 1;
• and
• wherein either
• A. (i) L is a linker selected from the group consisting of ε-D-Lys, ε-Lys, δ-D-Orn, δ-Orn, γ-aminobutyric acid, 8-aminooctanoic acid, 11-amino-undecanoic acid, 8-amino-3,6-dioxaoctanoic acid, 4-amino-4-carboxylic piperidine, and (D-Lys-Gly lactam)2, and
• (ii) the moieties Xaa1-Xaa2-Xaa3-(Xaa4)p and (Xaa1)q-(Xaa1)r-(Xaa3)s-(Xaa4)t are different from one another;
• or
• B. L is a linker selected from the group consisting of γ-aminobutyric acid, 8-aminooctanoic acid, 11-amino-undecanoic acid, 8-amino-3,6-dioxaoctanoic acid, 4-amino-4-carboxylic piperidine, and (D-Lys-Gly lactam)2.