DEUTERATED TETRAPEPTIDES THAT TARGET MITOCHONDRIA

1 . A compound of formula (I), or a pharmaceutically acceptable salt thereof:

Aaa 1 -Aaa 2 -Aaa 3 -Aaa 4 -NH 2   (I);

wherein:

Aaa 1 is an L-phenylalanine residue;

Aaa 2 is a D-arginine residue;

Aaa 3 is an L-phenylalanine residue;

Aaa 4 is an L-lysine residue; and

at least one hydrogen atom is replaced by a deuterium atom.

2 . The compound of claim 1 , wherein:

Aaa 1 is an L-phenylalanine residue or an amino acid residue selected from the group consisting of:

Aaa 2 is a D-arginine residue or an amino acid residue selected from the group consisting of:

Aaa 3 is an L-phenylalanine residue or an amino acid residue selected from the group consisting of:

and

Aaa 4 is an L-lysine residue or an amino acid residue selected from the group consisting of:

provided that the compound of formula (I) is not Phe-D-Arg-Phe-Lys-NH 2 .

3 . The compound of claim 1 or 2 , wherein Aaa 1 is selected from the group consisting of:

4 . The compound of any one of claims 1 - 3 , wherein Aaa 2 is selected from the group consisting of:

5 . The compound of any one of claims 1 - 4 , wherein Aaa 3 is selected from the group consisting of:

6 . The compound of any one of claims 1 - 5 , wherein Aaa 4 is selected from the group consisting of:

7 . The compound of claim 2 , selected from the following table:

8 . The compound of claim 7 , selected from the following table:

9 . A compound of formula (II), or a pharmaceutically acceptable salt thereof:

Aaa 5 -Aaa 6 -Aaa 7 -Aaa 8 -NH 2   (II);

wherein:

Aaa 5 is a D-arginine residue;

Aaa 6 is: OH;

Aaa 7 is an L-lysine residue;

Aaa 8 is an L-phenylalanine residue; and

at least one hydrogen atom is replaced by a deuterium atom.

10 . The compound of claim 9 , wherein:

Aaa 5 is a D-arginine residue or an amino acid residue selected from the group consisting of:

Aaa 6 is:

Aaa 7 is an L-lysine residue or an amino acid residue selected from the group consisting of:

and

Aaa 8 is an L-phenylalanine residue or an amino acid residue selected from the group consisting of:

provided that the compound of formula (II) is not D-Arg-DMT-Lys-Phe-NH 2 ; wherein DMT represents

11 . The compound of claim 9 or 10 , wherein Aaa 5 is an amino acid residue selected from the group consisting of:

12 . The compound of any one of claims 9 - 11 , wherein Aaa 7 is an amino acid residue selected from the group consisting of:

13 . The compound of any one of claims 9 - 12 , wherein Aaa 8 is an amino acid residue selected from the group consisting of:

14 . The compound of claim 10 , selected from the following table:

15 . The compound of claim 14 , selected from the following table:

16 . A pharmaceutical composition, comprising a compound of any one of claims 1 - 15 ;

and a pharmaceutically acceptable carrier.

17 . A method for treating or preventing ischemia-reperfusion injury in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a compound of any one of claims 1 - 15 .

18 . The method of claim 17 , wherein the ischemia-reperfusion injury is cardiac ischemia-reperfusion injury.

19 . A method for treating or preventing a myocardial infarction in a subject in need thereof comprising administering to the subject a therapeutically effective amount of a compound of any one of claims 1 - 15 .

20 . The method of any one of claims 17 - 19 , wherein the compound is administered orally, topically, systemically, intravenously, subcutaneously, intraperitoneally, or intramuscularly.