Reactive oxygen species scavengers and use for treating diseases
A compound of Formula (I), pharmaceutically acceptable salts thereof, and individual enantiomers or diastereomers thereof. Compositions and methods useful for treatment or suppression of diseases, developmental delays and symptoms related to oxidative stress.
1. A compound selected from:
or a pharmaceutically acceptable salt of any of the foregoing.
2. The compound of claim 1 , wherein the compound has the structure of Formula (III) (methyl (2S)—2-{[(2S)-1-1-[(2S,3E,5S)-2-benzyl-5-{[(tert-butoxy) carbonyl]amino}-7-methyloct-3-enoyl]pyrrolidin-2-yl]formamido}-5-({[(1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl)oxy]carbonyl}amino)pentanoate):
or a pharmaceutically acceptable salt thereof.
3. The compound of claim 1 , wherein the compound has the structure of Formula (XXVIII) (tert-butyl N—[(4S,5E,7S)-7-benzyl-8-[(2S)—2-{[(1S)-1-carbamoyl-4-({[(1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl)oxy]carbonyl}amino-)butyl]carbamoyl}pyrrolidin-1-yl]-2-methyl-8-oxooct-5-en-4-yl]carbamate);
or a pharmaceutically acceptable salt thereof.
4. The compound of claim 1 , wherein the compound has the structure of Formula (XXIX) ((2S)—2-{[(2S)—1-[(2S,3E,5S)-2-benzyl-5-{[(tert-butoxy)carbonyl]amino}-7-methyloct-3-enoyl]pyrrolidin-2-yl]formamido}-5-({[(1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl)oxy]carbonyl}amino)pentanoate):
or a pharmaceutically acceptable salt thereof.
5. The compound of claim 1 , wherein the compound has the structure of Formula (XXX) (propan-2-yl (2S)—2-{[(2S)-1-[(2S,3E,5S)-2-benzyl-5-{[(tert-butoxy)carbonyl] amino}-7-methyloct-3-enoyl]pyrrolidin-2-yl]formamido}-5-({[(1-hydroxy-2,2,6,6-tetramethylpiperidin-4-yl)oxy]carbonyl}amino)pentanoate):
or a pharmaceutically acceptable salt thereof.
6. The compound of claim 1 , wherein the compound has the structure of Formula (XXXI) (propan-2-yl (2S)—2-{[(2S)-1-[(2S,3E,5S)-2-benzyl-5-{[(tert-butoxy) carbonyl]amino}-7-methyloct-3-enoyl]pyrrolidin-2-yl]formamido}-6-({[(1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl)oxy]carbonyl}amino)hexanoate):
or a pharmaceutically acceptable salt thereof.
7. The compound of claim 1 , wherein the compound has the structure of Formula (XXXII) (propan-2-yl (2S)-2-1[(2S)-1-[(2S,3E,5S)-2-benzyl-5-{[(tert-butoxy) carbonyl]amino 1-7-methyloct-3-enoyl]pyrrolidin-2-yl]formamido}-6-[(1-oxyl-2,2,5,5-tetramethylpyrrolidin-3-yl)formamido]-hexanoate):
or a pharmaceutically acceptable salt thereof.
8. The compound of claim 1 , wherein the compound has the structure of Formula (XXXIII) ((2R)—2-{[(2S)— 1-[(2S,3E,5S)-2-benzyl-5{[(tert-butoxy)carbonyl]amino}-7-methyloct-3-enoyl]pyrrolidin-2-yl]formamido}-6-({[(1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl)oxy]carbonyl}amino)hexanoate):
or a pharmaceutically acceptable salt thereof.
9. The compound of claim 1 , wherein the compound has the structure of Formula (XXXIV) ((2R)—2-{[(2S)-1-[(2S,3E,5S)-2-benzyl-5-{[(tert-butoxy)carbonyl]amino}-7-methyloct-3-enoyl]pyrrolidin-2-yl]formamido}-6-({[(1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl)oxy]carbonyl}amino)hexanoic acid):
or a pharmaceutically acceptable salt thereof.
10. The compound of claim 1 , wherein the compound has the structure of Formula (XXXV) (tert-butyl N—[(4S,5E,7S)-7-benzyl-8-[(2S)-2-{[(1S)-1-(diethylcarbamoyl)-4-({[(1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl)oxy]carbonyl}amino)-butyl]carbamoyl}pyrrolidin-1-yl]-2-methyl-8-oxooct-5-en-4-yl]carbamate):
or a pharmaceutically acceptable salt thereof.
11. The compound of claim 1 , wherein the compound has the structure of Formula (XXXVI) (tert-butyl N-{(4S,5E,7S)-7-benzyl-8-[(2S)—2-{[(1 S)-1-(tert-butylcarbamoyl)-5-({[(1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl)oxy]carbonyl}amino)pentyl]-carbamoyl}pyrrolidin-1-yl]-2-methyl-8-oxooct-5-en-4-yl carbamate):
or a pharmaceutically acceptable salt thereof.
12. The compound of claim 1 , wherein the compound has the structure of Formula (XXXVII) (tert-butyl N—[(4S,5E,7S)-7-benzyl-8-[(2S)-2-{[1S)-5-({[(1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl)oxy]carbonyl}amino)-1-[(propan-2-yl)carbamoyl]pentyl]carbamoyl}pyrrolidin-1-yl]-2-methyl-8-oxooct-5-en-4-yl]carbamate):
or a pharmaceutically acceptable salt thereof.
13. The compound of claim 1 , wherein the compound has the structure of Formula (XXXVIII) ((S)-methyl 2-((S)-2-((S)-1-((2S,5S,E)-2-benzyl-5-((tert-butoxycarbonyl)amino)-7-methyloct-3-enoyl)pyrrolidine-2-carboxamido)-3-methylbutanamido)—5-((((l-oxyl-2,2,6,6-tetramethylpiperidin-4-yl)oxy)carbonyl)amino)pentanoate):
or a pharmaceutically acceptable salt thereof.
14. The compound of claim 1 , wherein the compound has the structure of Formula (XXXIX) ((S)-methyl 2-((S)-2-((S)-1-((2S,5S,E)-2-benzyl-5-((tert-butoxycarbonyl)amino)-7-methyloct-3-enoyl)pyrrolidine-2-carboxamido)-3-methylbutanamido)—5-((((l-hydroxy-2,2,6,6-tetramethylpiperidin-4-yl)oxy)carbonyl)amino)pentanoate):
or a pharmaceutically acceptable salt thereof.
15. The compound of claim 1 , wherein the compound has the structure of Formula (XXXXIV) (tert-butyl N—[(4S,5E,7S)-7-benzyl-8-[(2S)-2-{[(1S)-4-({[(1-oxyl-2,2,6,6-tetramethylpiperidin-4-yl)oxy]carbonyl}amino)-1-[(propan-2-yl) carbamoyl]butyl]carbamoyl}pyrrolidin-1-yl]-2-methyl-8-oxooct-5-en-4-yl]carbamate):
or a pharmaceutically acceptable salt thereof.
16. The compound of claim 1 , wherein the compound has the structure of Formula (XXXXV) (tert-butyl N—[(4S,5E,7S)-7-benzyl-8-[(2S)-2-{[(1S)-4-({[(1-hydroxy-2,2,6,6-tetramethylpiperidin-4-yl)oxy]carbonyl}amino)-1-[(propan-2-yl) carbamoyl]butyl]carbamoyl}pyrrolidin-1-yl]-2-methyl-8-oxooct-5-en-4-yl]carbamate):
or a pharmaceutically acceptable salt thereof.
17. The compound of claim 1 , wherein the compound has the structure of Formula (XXXXVI) ((S)—cyclohexyl 2-((R)-1-((2S,5S,E)-2-benzyl-5-((tert-butoxycarbonyl)amino)-7-methyloct-3-enoyl)pyrrolidine-2-carboxamido)-6-((((l-hydroxy-2,2,6,6-tetramethylpiperidin-4-yl)oxy)carbonyl)amino)hexanoate):
or a pharmaceutically acceptable salt thereof.
18. The compound of claim 1 , wherein the compound has the structure of Formula (XXXXVII) (tert-butyl N— [(4S,5E,7S)-7-benzyl-8-[(2S)—2-{[(1S)—1-{[(1S)-4-({[(1-oxyl- 2,2,6,6-tetramethylpiperidin-4-yl)oxy]carbonyl}amino)-1-[(propan-2-yl)carbamoyl]butyl}carbamoyl]-2-methylpropyl]carbamoyl}pyrrolidin-1-yl]-2-methyl-8-oxooct-5-en-4-yl]carbamate):
or a pharmaceutically acceptable salt thereof.
19. A pharmaceutical composition comprising the compound of claim 1 or a pharmaceutically acceptable salt thereof.
20. A method of treating acute kidney injury in a patient comprising administering to a patient in need thereof a therapeutically effective amount of the compound of claim 1 or a pharmaceutically acceptable salt thereof.
21. A method of treating acute kidney injury in a patient comprising administering to a patient in need thereof a therapeutically effective amount of the pharmaceutical composition of claim 19 .
22. A compound selected from:
or a pharmaceutically acceptable salt of any of the foregoing.
23. A pharmaceutical composition comprising the compound of claim 22 or a pharmaceutically acceptable salt thereof.
24. A method of treating acute kidney injury in a patient comprising administering to a patient in need thereof a therapeutically effective amount of the compound of claim 22 or a pharmaceutically acceptable salt thereof.
25. A method of treating acute kidney injury in a patient comprising administering to a patient in need thereof a therapeutically effective amount of the pharmaceutical composition of claim 23 .