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US 8,716,486 B2Granted
2-heterocyclylaminoalkyl-(p-quinone) derivatives for treatment of oxidative stress diseases
AssigneeEdison Pharmaceuticals, Inc.
InventorsAndrew W. Hinman, Orion D. Jankowski, Kieron E. Wesson
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Abstract
Methods of treating or suppressing oxidative stress disorders including mitochondrial diseases, impaired energy processing disorders, neurodegenerative diseases and diseases of aging are disclosed, as well as compounds useful in the methods of the invention, such as 2-heterocyclylaminoalkyl-(p-quinone) derivatives.
Claims31
A method of treating or suppressing an oxidative stress disorder, comprising administering to a subject in need thereof a therapeutically effective amount of one or more compounds of Formula I:
- where R is selected from the group consisting of:
- where the * indicates the point of attachment of R to the remainder of the molecule;
- n is 0 or 1;
- R1 and R2 are independently selected from the group consisting of hydrogen, (C1-C6)alkyl, and (C1-C6)alkoxy;
- R3 is (C1-C6)alkyl or (C1-C6)alkoxy;
- R4 is hydrogen, (C1-C6)alkyl, hydroxy, or (C1-C6)alkoxy;
- Het is optionally substituted pyridine;
- M and M′ are independently selected from the group consisting of hydrogen, —C(O)—R10, —C(O)(C2-C6)-alkenyl, —C(O)(C2-C6)-alkynyl, —C(O)-aryl, —C(O)-heterocyclyl, —C(O)O—R10, —C(O)NR10aR10b, —SO2OR10, —SO2—C1-C6-alkyl, —SO2—(C1-C6)-haloalkyl, —SO2-aryl, —SO2—NR10aR10b, —P(O)(OR10a)(OR10b), and C-linked amino acid or di-peptide, and
- R10, R10a, and R10b are independently hydrogen or (C1-C6)-alkyl optionally substituted with —OH, —NH2, —NH(C1-C4 alkyl), —N(C1-C4 alkyl)2, —C(O)OH, —C(O)O—(C1-C4)-alkyl or halogen;
- or a pharmaceutically acceptable salt, a solvate, or a hydrate thereof;
- wherein the oxidative stress disorder is selected from the group consisting of Leber's Hereditary Optic Neuropathy (LHON);
- Friedreich's Ataxia (FA);
- CoQ10 deficiency;
- Parkinson's disease;
- Huntington's Disease;
- and diabetes.
13 more elements
A compound of Formula I
- where R is selected from the group consisting of:
- where the * indicates the point of attachment of R to the remainder of the molecule;
- n is 0 or 1;
- R1 and R2 are independently selected from the group consisting of hydrogen, (C1-C6)alkyl, and (C1-C6)alkoxy;
- R3 is (C1-C6)alkyl or (C1-C6)alkoxy;
- R4 is hydrogen, (C1-C6)alkyl, hydroxy, or (C1-C6)alkoxy;
- Het is optionally substituted pyridine;
- M and M′ are independently selected from the group consisting of hydrogen, —C(O)—R10, —C(O)(C2-C6)-alkenyl, —C(O)(C2-C6)-alkynyl, —C(O)-aryl, —C(O)-heterocyclyl, —C(O)O—R10, —C(O)NR10aR10b, —SO2OR10, —SO2—C1-C6-alkyl, —SO2—(C1-C6)-haloalkyl, —SO2-aryl, —SO2—NR10aR10b, —P(O)(OR10a)(OR10b), and C-linked amino acid or di-peptide, and
- R10, R10a, and R10b are independently hydrogen or (C1-C6)-alkyl optionally substituted with —OH, —NH2, —NH(C1-C4 alkyl), —N(C1-C4 alkyl)2, —C(O)OH, —C(O)O—(C1-C4)-alkyl or halogen;
- or a salt, a solvate, or a hydrate thereof.
7 more elements
A compound of Formula Ia:
- where:
- n is 0 or 1;
- R1 and R2 are independently selected from the group consisting of hydrogen, (C1-C6)alkyl, and (C1-C6)alkoxy;
- R3 is (C1-C6)alkyl or (C1-C6)alkoxy;
- R4 is hydrogen, (C1-C6)alkyl, hydroxy, or (C1-C6)alkoxy;
- Het is pyridine optionally substituted with (C1-C6)alkyl, (C1-C6)haloalkyl, halogen, nitro, cyano, —C(O)(C1-C4)alkyl, —C(O)(C1-C6)cycloalkyl, —C(O)OH, —C(O)O(C1-C4)-alkyl or oxo;
- or a salt, a solvate, or a hydrate thereof.
4 more elements
A compound of formula Ib
- where:
- n is 0 or 1;
- R1 and R2 are independently selected from the group consisting of hydrogen, (C1-C6)alkyl, and (C1-C6)alkoxy;
- R3 is (C1-C6)alkyl or (C1-C6)alkoxy;
- R4 is hydrogen, (C1-C6)alkyl, hydroxy, or (C1-C6)alkoxy;
- Het is pyridine optionally substituted with (C1-C6)alkyl, (C1-C6)haloalkyl, halogen, nitro, cyano, —C(O)(C1-C4)alkyl, —C(O)(C1-C6)cycloalkyl, —C(O)OH, —C(O)O(C1-C4)-alkyl or oxo;
- M and M′ are independently selected from the group consisting of hydrogen, —C(O)—R10, —C(O)(C2-C6)-alkenyl, —C(O)(C2-C6)-alkynyl, —C(O)-aryl, —C(O)-heterocyclyl, —C(O)O—R10, —C(O)NR10aR10b, —SO2OR10, —SO2—C1-C6-alkyl, —SO2—(C1-C6)-haloalkyl, —SO2-aryl, —SO2—NR10aR10b, —P(O)(OR10a)(OR10b) and C-linked amino acid or di-peptide, and
- R10, R10a, and R10b are independently hydrogen or (C1-C6)-alkyl optionally substituted with —OH, —NH2, —NH(C1-C4 alkyl), —N(C1-C4 alkyl)2, —C(O)OH, —C(O)O—(C1-C4)-alkyl or halogen;
- or a salt, a solvate, or a hydrate thereof.
6 more elements
Dependencies are inferred from the claim text.