ANALOGS THAT TARGET MITOCHONDRIAL DISEASES
Disclosed are analogs of elamipretide (MTP-131). The compounds are useful for the treatment and prevention of ischemia-reperfusion injury (e.g., cardiac ischemia-reperfusion injury) or myocardial infarction.
1 - 25 . (canceled)
26 . 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 formula (I), or a pharmaceutically acceptable salt thereof:
wherein:
Aaa 1 is an amino acid residue selected from the group consisting of:
Aaa 2 is an amino acid residue selected from the group consisting of:
Aaa 3 is an amino acid residue selected from the group consisting of:
Aaa 4 is an amino acid residue selected from the group consisting of:
wherein R 1a , R 1b , R 1e , R 1x , R 2a , R 2b , R 3a , R 3b , R 3c , R 4a , and R 4b are each independently selected from the group consisting of H, methyl, ethyl, propyl, cyclopropyl, cyclobutyl, and (C 1 -C 6 )alkyl; or R 1a and R 1x together with the N atom to which they are attached form a 4-6-membered heterocyclyl; and
R a , R b , R 1c and R 1d are each independently selected from the group consisting of H, methyl, ethyl, propyl, cyclopropyl, cyclobutyl, (C 1 -C 6 )alkyl, C(O)((C 1 -C 6 )alkyl), C(O)((C 1 -C 6 )haloalkyl), C(O)O((C 1 -C 6 )alkyl), and C(O)O(aryl(C 1 -C 6 )alkyl); or R a and R b together with the N atom to which they are attached form a 4-6-membered heterocyclyl.
27 . The method of claim 26 , wherein R 1a and R 1x are independently H, methyl, ethyl, propyl, cyclopropyl, or cyclobutyl; or R 1a and R 1x together with the N atom to which they are attached form a 4-6-membered heterocyclyl.
28 . The method of claim 26 , wherein R a and R b are each independently H or methyl.
29 . The method of claim 26 , wherein R a and R b are each H.
30 . The method of claim 26 , wherein R 2a and R 2b are each independently H or methyl.
31 . The method of claim 26 , wherein R 3a and R 3b are each independently H or methyl.
32 . The method of claim 26 , wherein R 4a and R 4b are each independently H or methyl.
33 . The method of claim 26 , wherein Aaa 1 is selected from the group consisting of
34 . The method of claim 26 , wherein Aaa 1 is
35 . The method of claim 26 , wherein Aaa 1 is
36 . The method of claim 26 , wherein Aaa 2 is selected from the group consisting of:
37 . The method of claim 26 , wherein Aaa 2 is
38 . The method of claim 26 , wherein Aaa 3 is selected from the group consisting of:
39 . The method of claim 26 , wherein Aaa 3 is selected from the group consisting of:
40 . The method of claim 26 , wherein Aaa 3 is
41 . The method of claim 26 , wherein Aaa 3 is
42 . The method of claim 26 , wherein Aaa 4 is selected from the group consisting of:
43 . The method of claim 26 , wherein Aaa 4 is selected from the group consisting of:
44 . The method of claim 26 , wherein the compound or formula (I), or a pharmaceutically acceptable salt thereof, is selected from the following table:
45 . The method of claim 26 , wherein the compound of formula (I), or a pharmaceutically acceptable salt thereof, is represented by:
46 . The method of claim 26 , wherein the ischemia-reperfusion injury is cardiac ischemia-reperfusion injury.
47 . The method of claim 26 , wherein the compound is administered orally, topically, systemically, intravenously, subcutaneously, intraperitoneally, or intramuscularly.