2-SUBSTITUTED AMINO-NAPHTH (1,2-D) IMIDAZOL-5-ONE COMPOUNDS OR PHARMACEUTICALLY ACCEPTABLE SALTS THEREOF

• US 20190330159A1
• Filed: 11/15/2017
• Published: 10/31/2019
• Est. Priority Date: 11/15/2016
• Status: Active Grant

• Current Assignee: PTC Therapeutics, Inc.
• Original Assignee: BioElectron Technology Corporation (PTC Therapeutics, Inc.)
• Inventors: KITANO, Hiroyuki, MORI, Kazuto
• Granted Patent: US 10,738,014 B2
• Time in Patent Office: Days
• CPC Class Codes: A61P 25/00 Drugs for disorders of the nervous system
• CPC Class Codes: C07D 233/88 Nitrogen atoms, e.g. allantoin
• CPC Class Codes: C07D 235/02 condensed with carbocyclic rings or ring systems
• CPC Class Codes: C07D 401/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 401/14 containing three or more hetero rings
• CPC Class Codes: C07D 403/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 403/10 linked by a carbon chain containing aromatic rings
• CPC Class Codes: C07D 403/14 containing three or more hetero rings
• CPC Class Codes: C07D 405/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 407/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 413/04 directly linked by a ring-member-to-ring-member bond
• CPC Class Codes: C07D 413/10 linked by a carbon chain containing aromatic rings
• CPC Class Codes: C07D 413/14 containing three or more hetero rings
• CPC Class Codes: C07D 417/04 directly linked by a ring-member-to-ring-member bond

Abstract

Provided herein are therapeutic and/or prophylactic compounds for mitochondrial or oxidative stress diseases such as cancer, amyotrophic lateral sclerosis, Creutzfeldt-Jakob disease, Machado-Joseph disease, spinocerebellar ataxia, Huntington disease, Parkinson disease, Alzheimer disease, myocardial infarction, cerebral infarction, diseases related to aging, diabetes, alcoholic liver injury, chronic obstructive pulmonary disease, mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), and the like, wherein the compound is represented by formula (1), or reduced forms thereof, or pharmaceutically acceptable salts thereof.

Claims

1. A compound according to formula (1):

2. The compound according to claim 1 or a reduced form thereof, or a pharmaceutically acceptable salt thereof, wherein R¹ and R² are each independently

(1) a hydrogen atom,

(2) a C_1-6alkyl group, an optionally substituted C_2-6alkenyl group, or an optionally substituted C_2-6alkynyl group (wherein each group is optionally substituted with one to three substituents independently selected from the group consisting of a halogen atom, a C_1-6alkoxy group, a C_3-6cycloalkyl group, and a hydroxyl group),

(3) a C_3-10alicyclic hydrocarbon group (wherein the group may contain one or more unsaturated bonds and the group is optionally substituted with one to three substituents independently selected from the group consisting of a C_1-6alkyl group, a halogen atom, a C_1-6alkoxy group, a C_3-6cycloalkyl group, and a hydroxyl group),

(4) a 3 to 8-membered saturated heterocyclic group (wherein the group may contain one or more unsaturated bonds and the group is optionally substituted with one to four groups independently selected from the group consisting of

(a) a halogen atom,

(b) a C_1-6alkyl group (wherein the group is optionally substituted with one to three halogen atoms),

(c) a C_1-6alkoxy group (wherein the group is optionally substituted with one to three halogen atoms), and

(d) an amino group (wherein the group is optionally substituted with one or two C_1-6alkyl groups), with the proviso that in the 3 to 8-membered saturated heterocyclic group, a carbon atom on its ring is bonded with the nitrogen atom to which R¹ and R² are attached),

(5) a C_6-10aryl group (wherein the group is optionally substituted with one to four groups independently selected from the group consisting of

(a) a halogen atom,

(b) a C_1-6alkyl group (wherein the group is optionally substituted with one to three halogen atoms),

(c) a C_1-6alkoxy group (wherein the group is optionally substituted with one to three halogen atoms), and

(d) an amino group (wherein the group is optionally substituted with one or two C_1-6alkyl groups)), or

(6) a 5 to 12-membered monocyclic or polycyclic heteroaryl group (wherein the group is optionally substituted with one to four groups independently selected from the group consisting of

(a) a halogen atom,

(b) a C_1-6alkyl group (wherein the group is optionally substituted with one to three halogen atoms),

(c) a C_1-6alkoxy group (wherein the group is optionally substituted with one to three halogen atoms), and

(d) an amino group (wherein the group is optionally substituted with one or two C_1-6alkyl groups), with the proviso that in the 5 to 12-membered monocyclic or polycyclic heteroaryl group, a carbon atom on its ring is bonded with the nitrogen atom to which R¹ and R² are attached), or R¹ and R² may be taken together with the nitrogen atom to which they are attached to form a 3 to 8-membered, nitrogen-containing heterocycle (wherein the heterocycle may contain one or more unsaturated bonds and the heterocycle is optionally substituted with one or two groups independently selected from the group consisting of a halogen atom, a C_1-6alkyl group, a C_1-6alkoxy group, and a hydroxyl group);

R³ is

(1) a C_6-10aryl group (wherein the group is optionally substituted with one to seven substituents independently selected from the group consisting of

(a) a halogen atom,

(b) a hydroxyl group,

(c) a cyano group,

(d) a C_1-6alkylsulfonyl group (wherein the group is optionally substituted with one to three substituents independently selected from the group consisting of a halogen atom, a C_1-6alkoxy group, a C_3-6cycloalkyl group, and a hydroxyl group),

(e) a C_1-6alkylaminosulfonyl group (wherein each C_1-6alkyl group is optionally substituted with one to three substituents independently selected from the group consisting of a halogen atom, a C_1-6alkoxy group, a C_3-6cycloalkyl group, and a hydroxyl group),

(f) a C_1-6alkylcarbonyl group (wherein the group is optionally substituted with one to three substituents independently selected from the group consisting of a halogen atom, a C_1-6alkoxy group, a C_3-6cycloalkyl group, and a hydroxyl group),

(g) a C_1-6alkyl group (wherein the group is optionally substituted with one to three substituents independently selected from the group consisting of a halogen atom, a C_1-6alkoxy group, a C_3-6cycloalkyl group, and a hydroxyl group),

(h) a C_1-6alkoxy group (wherein the group is optionally substituted with one to three substituents independently selected from the group consisting of a halogen atom, a C_1-6alkoxy group, a C_3-6cycloalkyl group, and a hydroxyl group),

(i) a C_3-10cycloalkoxy group (wherein the group is optionally substituted with one to three substituents independently selected from the group consisting of a halogen atom, a C_1-6alkoxy group, a C_3-6cycloalkyl group, and a hydroxyl group),

(j) —

N(R⁴)COR⁵,

(k) —

CONR⁶R⁷,

(l) —

S(O)₂NR⁸R⁹,

(m) an amino group (wherein the group is optionally substituted with one or two C_1-6alkyl groups), and

(n) a 4 to 7-membered cyclic amino group (wherein the group is optionally substituted with one or two C_1-6alkyl groups), or two or more substituents on the C_6-10aryl group may be joined to form a 5 to 8-membered non-aromatic carbocyclic or heterocyclic ring (wherein the 9 to 16-membered ring is optionally substituted with one or two C_1-6alkyl groups)), or

(2) a 5 to 12-membered monocyclic or polycyclic heteroaryl group (wherein the group is optionally substituted with one to nine substituents independently selected from the group consisting of

(a) a halogen atom,

(b) a hydroxyl group,

(c) a cyano group,

(d) a C_1-6alkylsulfonyl group (wherein the group is optionally substituted with one to three substituents independently selected from the group consisting of a halogen atom, a C_1-6alkoxy group, a C_3-6cycloalkyl group, and a hydroxyl group),

(e) a C_1-6alkylaminosulfonyl group (wherein each C_1-6alkyl group is optionally substituted with one to three substituents independently selected from the group consisting of a halogen atom, a C_1-6alkoxy group, a C_3-6cycloalkyl group, and a hydroxyl group),

(f) a C_1-6alkylcarbonyl group (wherein the group is optionally substituted with one to three substituents independently selected from the group consisting of a halogen atom, a C_1-6alkoxy group, a C_3-6cycloalkyl group, and a hydroxyl group),

(g) a C_1-6alkyl group (wherein the group is optionally substituted with one to three substituents independently selected from the group consisting of a halogen atom, a C_1-6alkoxy group, a C_3-6cycloalkyl group, and a hydroxyl group),

(h) a C_1-6alkoxy group (wherein the group is optionally substituted with one to three substituents independently selected from the group consisting of a halogen atom, a C_1-6alkoxy group, a C_3-6cycloalkyl group, and a hydroxyl group),

(i) a C_3-10cycloalkoxy group (wherein the group is optionally substituted with one to three substituents independently selected from the group consisting of a halogen atom, a C_1-6alkoxy group, a C_3-6cycloalkyl group, and a hydroxyl group),

(j) a C_6-10aryl group (wherein the group is optionally substituted with one to three substituents independently selected from the group consisting of a halogen atom, a C_1-6alkoxy group, a C_3-6cycloalkyl group, and a hydroxyl group),

(k) —

N(R¹⁰)COR¹¹,

(l) —

CONR¹²R¹³,

(m) an amino group (wherein the group is optionally substituted with one or two C_1-6alkyl groups), and

(n) a 4 to 7-membered cyclic amino group (wherein the group is optionally substituted with one or two C_1-6alkyl groups), or two or more substituents on the 5 to 12-membered monocyclic or polycyclic heteroaryl group may be joined to form a 5 to 8-membered non-aromatic carbocyclic or heterocyclic ring (wherein the 8 to 18-membered ring is optionally substituted with one or two C_1-6alkyl groups), with the proviso that in the 5 to 12-membered monocyclic or polycyclic heteroaryl group, a carbon atom on its ring is bonded with the carbon atom to which R³ is attached); and

R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², and R¹³ are each independently a hydrogen atom or a C_1-10alkyl group optionally substituted with one to five fluorine atoms, or R⁶ and R⁷, R⁸ and R⁹, and R¹² and R¹³ each independently may be taken together to form a 4 to 10-membered, nitrogen-containing heterocycle.

3. The compound according to claim 1 or a reduced form thereof, or a pharmaceutically acceptable salt thereof, wherein R³ is

(1) a C_6-10aryl group (wherein the group is optionally substituted with one to seven substituents independently selected from the group consisting of

(a) a halogen atom,

(b) a cyano group,

(c) a C_1-6alkyl group (wherein the group is optionally substituted with one to three substituents independently selected from the group consisting of a halogen atom, a C_1-6alkoxy group, a C_3-6cycloalkyl group, and a hydroxyl group),

(d) a C_1-6alkoxy group (wherein the group is optionally substituted with one to three substituents independently selected from the group consisting of a halogen atom, a C_1-6alkoxy group, a C_3-6cycloalkyl group, and a hydroxyl group),

(e) a C_3-10cycloalkoxy group (wherein the group is optionally substituted with one to three substituents independently selected from the group consisting of a halogen atom, a C_1-6alkoxy group, a C_3-6cycloalkyl group, and a hydroxyl group),

(f) —

N(R⁴)COR⁵,

(g) —

CONR⁶R⁷,

(h) —

S(O)₂NR⁸R⁹,

(i) an amino group (wherein the group is optionally substituted with one or two C_1-6alkyl groups), and

(j) a 4 to 7-membered cyclic amino group (wherein the group is optionally substituted with one or two C_1-6alkyl groups), or

two substituents on the C_6-10aryl group may be joined to form a 5 to 8-membered non-aromatic carbocyclic or heterocyclic ring (wherein the 9 to 16-membered ring is optionally substituted with one or two C_1-6alkyl groups;

or in some embodiments, the 5 to 8-membered non-aromatic carbocyclic or heterocyclic ring is optionally substituted with one or two C_1-6alkyl groups)), or

(2) a 5 to 12-membered monocyclic or polycyclic heteroaryl group (wherein the group is optionally substituted with one to nine substituents independently selected from the group consisting of

(a) a C_1-6alkyl group (wherein the group is optionally substituted with one to three substituents independently selected from the group consisting of a halogen atom, a C_1-6alkoxy group, a C_3-6cycloalkyl group, and a hydroxyl group),

(b) a C_1-6alkoxy group (wherein the group is optionally substituted with one to three substituents independently selected from the group consisting of a halogen atom, a C_1-6alkoxy group, a C_3-6cycloalkyl group, and a hydroxyl group),

(c) a C_3-10cycloalkoxy group (wherein the group is optionally substituted with one to three substituents independently selected from the group consisting of a halogen atom, a C_1-6alkoxy group, a C_3-6cycloalkyl group, and a hydroxyl group),

(d) a C_6-10aryl group (wherein the group is optionally substituted with one to three substituents independently selected from the group consisting of a halogen atom, a C_1-6alkoxy group, a C_3-6cycloalkyl group, and a hydroxyl group),

(e) —

N(R¹⁰)COR¹¹,

(f) —

CONR¹²R¹³,

(g) an amino group (wherein the group is optionally substituted with one or two C_1-6alkyl groups), and

(h) a 4 to 7-membered cyclic amino group (wherein the group is optionally substituted with one or two C_1-6alkyl groups), or

two substituents on the 5 to 12-membered monocyclic or polycyclic heteroaryl group may be joined to form a 5 to 8-membered non-aromatic carbocyclic or heterocyclic ring (wherein the 8 to 18-membered ring is optionally substituted with one or two C_1-6alkyl groups;

or in some embodiments, the 5 to 8-membered non-aromatic carbocyclic or heterocyclic ring is optionally substituted with one or two C_1-6alkyl groups),

with the proviso that in the 5 to 12-membered monocyclic or polycyclic heteroaryl group, a carbon atom on its ring is bonded with the carbon atom to which R³ is attached); and

R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², and R¹³ are each independently a hydrogen atom or a C_1-10alkyl group optionally substituted with one to five fluorine atoms, or R⁶ and R⁷, R⁸ and R⁹, and R¹² and R¹³ each independently may be taken together to form a 4 to 10-membered, nitrogen-containing heterocycle.

4. The compound according to claim 1 or a reduced form thereof, or a pharmaceutically acceptable salt thereof, wherein R³ is

(1) a C_6-10aryl group (wherein the group is optionally substituted with one to seven substituents independently selected from the group consisting of

(a) a halogen atom,

(b) a cyano group,

(c) a C_1-6alkyl group (wherein the group is optionally substituted with one to three substituents independently selected from the group consisting of a halogen atom and a C_1-6alkoxy group),

(d) a C_1-6alkoxy group (wherein the group is optionally substituted with one to three halogen atoms),

(e) —

N(R⁴)COR⁵,

(f) —

CONR⁶R⁷,

(g) —

S(O)₂NR⁸R⁹,

(h) an amino group (wherein the group is optionally substituted with one or two C_1-6alkyl groups), and

(i) a 4 to 7-membered cyclic amino group (wherein the group is optionally substituted with one or two C_1-6alkyl groups), or

two substituents on the C_6-10aryl group may be joined to form a 5 to 8-membered non-aromatic heterocycle (wherein the 5 to 8-membered non-aromatic heterocycle is optionally substituted with one or two C_1-6alkyl groups)), or

(2) a 5 to 12-membered monocyclic or polycyclic heteroaryl group (wherein the group is optionally substituted with one to nine substituents independently selected from the group consisting of

(a) a C_1-6alkyl group,

(b) a C_1-6alkoxy group,

(c) a C_3-10cycloalkoxy group,

(d) a C_6-10aryl group,

(e) —

N(R¹⁰)COR¹¹,

(f) —

CONR¹²R¹³,

(g) an amino group (wherein the group is optionally substituted with one or two C_1-6alkyl groups), and

(h) a 4 to 7-membered cyclic amino group (wherein the group is optionally substituted with one or two C_1-6alkyl groups), or

two substituents on the 5 to 12-membered monocyclic or polycyclic heteroaryl group may be joined to form a 5 to 8-membered non-aromatic heterocycle (wherein the 5 to 8-membered non-aromatic heterocycle is optionally substituted with one or two C_1-6alkyl groups),

with the proviso that in the 5 to 12-membered monocyclic or polycyclic heteroaryl group, a carbon atom on its ring is bonded with the carbon atom to which R³ is attached); and

R⁴, R⁵, R⁶, R⁷, R⁸, R⁹, R¹⁰, R¹¹, R¹², and R¹³ are each independently a hydrogen atom or a C_1-10alkyl group, or R⁶ and R⁷, R⁸ and R⁹, and R¹² and R¹³ each independently may be taken together to form a 4 to 10-membered, nitrogen-containing heterocycle.

5. The compound according to claim 1 or a reduced form thereof, or a pharmaceutically acceptable salt thereof, wherein R¹ and R² are each independently

(1) a hydrogen atom,

(2) a C_1-6alkyl group (wherein the group is optionally substituted with one to three substituents independently selected from the group consisting of a halogen atom, a C_1-6alkoxy group, a C_3-6cycloalkyl group, and a hydroxyl group), or

(3) a C_3-10alicyclic hydrocarbon group (wherein the group may contain one or more unsaturated bonds and the group is optionally substituted with one to three substituents independently selected from the group consisting of a halogen atom, a C_1-6alkyl group, a C_1-6alkoxy group, a C_3-6cycloalkyl group, and a hydroxyl group), or

R¹ and R² are taken together with the nitrogen atom to which they are attached to form a 3 to 8-membered, nitrogen-containing heterocycle (wherein the heterocycle may contain one or more unsaturated bonds and the heterocycle is optionally substituted with one or two groups independently selected from the group consisting of a halogen atom, a C_1-6alkyl group, a C_1-6alkoxy group, and a hydroxyl group).

6. The compound according to claim 1 or a reduced form thereof, or a pharmaceutically acceptable salt thereof, wherein R¹ and R² are each independently a hydrogen atom, or a C_1-6alkyl group (wherein the group is optionally substituted with one to three C_1-6alkoxy groups), or

R¹ and R² are taken together with the nitrogen atom to which they are attached to form a 3 to 8-membered, nitrogen-containing heterocycle (wherein the heterocycle may contain one or more unsaturated bonds and the heterocycle is optionally substituted with one or two groups independently selected from the group consisting of a C_1-6alkyl group, a C_1-6alkoxy group, and a hydroxyl group).

7. The compound according to claim 1 or a reduced form thereof, or a pharmaceutically acceptable salt thereof, wherein

R¹ and R² are each independently an optionally substituted C_1-6alkyl group, or

R¹ and R² may be taken together with the nitrogen atom to which they are attached to form an optionally substituted, 3 to 8-membered, nitrogen-containing heterocycle (the heterocycle may contain one or more unsaturated bonds), and

R³ is an optionally substituted C_6-10aryl group, or an optionally substituted, 5 to 12-membered monocyclic or polycyclic heteroaryl group (with the proviso that in the group, a carbon atom on its ring is bonded with the carbon atom to which R³ is attached).

8. The compound according to claim 1 or a reduced form thereof, or a pharmaceutically acceptable salt thereof, wherein

R¹ and R² are each independently

a C_1-6alkyl group (wherein the group is optionally substituted with one C_1-6alkoxy group), or

R¹ and R² may be taken together with the nitrogen atom to which they are attached to form a 3 to 8-membered, nitrogen-containing heterocycle (wherein the heterocycle may contain one or more unsaturated bonds and the heterocycle is optionally substituted with one C_1-6alkyl group);

R³ is

(1) a C_6-10aryl group (wherein the group is optionally substituted with one to seven substituents independently selected from the group consisting of

(a) halogen atom,

(b) cyano group,

(c) a C_1-6alkyl group (wherein the group is optionally substituted with one to three substituents independently selected from the group consisting of a halogen atom and a C_1-6alkoxy group),

(d) a C_1-6alkoxy group (wherein the group is optionally substituted with one to three halogen atoms),

(e) —

N(R⁴)COR⁵,

(f) —

CONR⁶R⁷,

(g) —

S(O)₂NR⁸R⁹,

(h) an amino group (wherein the group is optionally substituted with one or two C_1-6alkyl groups), and

(i) a 4 to 7-membered cyclic amino group (wherein the group is optionally substituted with one or two C_1-6alkyl groups), or

two substituents on the C_6-10aryl group may be joined to form a 5 to 8-membered non-aromatic carbocyclic or heterocyclic ring (wherein the 9 to 16-membered ring is optionally substituted with one or two C_1-6alkyl groups;

or in some embodiments, the 5 to 8-membered non-aromatic carbocyclic or heterocyclic ring is optionally substituted with one or two C_1-6alkyl groups)), with the proviso that in the 5 to 12-membered monocyclic or polycyclic heteroaryl group, a carbon atom on its ring is bonded with the carbon atom to which R³ is attached), or

(2) a 5 to 12-membered monocyclic or polycyclic heteroaryl group (wherein the group is optionally substituted with one to nine substituents independently selected from the group consisting of

(a) a C_1-6alkyl group,

(b) a C_1-6alkoxy group,

(c) a C_6-10aryl group, and

(d) a 4 to 7-membered cyclic amino group (wherein the group is optionally substituted with one or two C_1-6alkyl groups),

with the proviso that in the 5 to 12-membered monocyclic or polycyclic heteroaryl group, a carbon atom on its ring is bonded with the carbon atom to which R³ is attached); and

R⁴, R⁵, R⁶, and R⁷ are each independently a hydrogen atom or a C_1-10alkyl group, and R⁸ and R⁹ may be taken together to form a 4 to 10-membered, nitrogen-containing heterocycle (wherein the heterocycle may contain one or more unsaturated bonds).

9. The compound according to claim 1 or a reduced form thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of the following compounds:

10. The compound according to claim 1 or a reduced form thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of the following compounds:

2-(dimethylamino)-4-(4-methylphenyl)-5H-naphth[1,2-d]imidazol-5-one;

2-(dimethylamino)-4-(2-methylphenyl)-5H-naphth[1,2-d]imidazol-5-one;

4-(2-methylphenyl)-2-(4-methylpiperazin-1-yl)-5H-naphth[1,2-d]imidazol-5-one;

2-(dimethylamino)-4-[2-(morpholin-4-yl)phenyl]-5H-naphth[1,2-d]imidazol-5-one;

2-(dimethylamino)-4-[2-(trifluoromethyl)phenyl]-5H-naphth[1,2-d]imidazol-5-one;

2-(dimethylamino)-4-[2-methyl-4-(trifluoromethyl)phenyl]-5H-naphth[1,2-d]imidazol-5-one;

2-(diethylamino)-4-(2-methylphenyl)-5H-naphth[1,2-d]imidazol-5-one;

2-(dimethylamino)-4-[2-methyl-4-(trifluoromethoxy)phenyl]-5H-naphth[1,2-d]imidazol-5-one;

4-(2-chlorophenyl)-2-(dimethylamino)-5H-naphth[1,2-d]imidazol-5-one;

2-(dimethylamino)-4-(1,3,5-trimethyl-1H-pyrazol-4-yl)-5H-naphth[1,2-d]imidazol-5-one;

2-[(2-dimethylamino)-5-oxo-5H-naphth[1,2-d]imidazol-4-yl]benzonitrile;

4-[(2-dimethylamino)-5-oxo-5H-naphth[1,2-d]imidazol-4-yl]-3-methylbenzonitrile; and

2-(dimethylamino)-4-(2-chloro-4-methoxyphenyl)-5H-naphth[1,2-d]imidazol-5-one.

11. A pharmaceutical composition comprising a compound according to claim 1, or a reduced form thereof, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable carrier.

13. A method of treating and/or preventing a disease caused by or aggravated by oxidative stress or mitochondrial dysfunction, characterized by administering to a patient in need of the treatment and/or prevention a therapeutically effective amount of a compound according to claim 1 or a reduced form thereof or a pharmaceutically acceptable salt thereof.

16. The compound according to claim 1 or a reduced form thereof, or a pharmaceutically acceptable salt thereof, wherein the compound is selected from the group consisting of the following compounds:

17. The compound according to claim 8 or a reduced form thereof, or a pharmaceutically acceptable salt thereof, wherein R¹ and R² are each independently a C_1-6alkyl group (wherein the group is optionally substituted with one C_1-6alkoxy group).

18. The compound according to claim 8 or a reduced form thereof, or a pharmaceutically acceptable salt thereof, wherein R¹ and R² taken together with the nitrogen atom to which they are attached to form a 3 to 8-membered, nitrogen-containing heterocycle (wherein the heterocycle may contain one or more unsaturated bonds and the heterocycle is optionally substituted with one C_1-6alkyl group).

19. The compound according to claim 8 or a reduced form thereof, or a pharmaceutically acceptable salt thereof, wherein

R³ is a C_6-10aryl group (wherein the group is optionally substituted with one to seven substituents independently selected from the group consisting of

(a) halogen atom,

(b) cyano group,

(c) a C_1-6alkyl group (wherein the group is optionally substituted with one to three substituents independently selected from the group consisting of a halogen atom and a C_1-6alkoxy group),

(d) a C_1-6alkoxy group (wherein the group is optionally substituted with one to three halogen atoms),

(e) —

N(R⁴)COR⁵,

(f) —

CONR⁶R⁷,

(g) —

S(O)₂NR⁸R⁹,

(h) an amino group (wherein the group is optionally substituted with one or two C_1-6alkyl groups), and

(i) a 4 to 7-membered cyclic amino group (wherein the group is optionally substituted with one or two C_1-6alkyl groups), or

two substituents on the C_6-10aryl group may be joined to form a 5 to 8-membered non-aromatic carbocyclic or heterocyclic ring (wherein the 9 to 16-membered ring is optionally substituted with one or two C_1-6alkyl groups;

or in some embodiments, the 5 to 8-membered non-aromatic carbocyclic or heterocyclic ring is optionally substituted with one or two C_1-6alkyl groups)); and

R⁴, R⁵, R⁶, and R⁷ are each independently a hydrogen atom or a C_1-10alkyl group, and R⁸ and R⁹ may be taken together to form a 4 to 10-membered, nitrogen-containing heterocycle (wherein the heterocycle may contain one or more unsaturated bonds).

20. The compound according to claim 8 or a reduced form thereof, or a pharmaceutically acceptable salt thereof, wherein R³ is a 5 to 12-membered monocyclic or polycyclic heteroaryl group (wherein the group is optionally substituted with one to nine substituents independently selected from the group consisting of

(a) a C_1-6alkyl group,

(b) a C_1-6alkoxy group,

(c) a C_6-10aryl group, and

(d) a 4 to 7-membered cyclic amino group (wherein the group is optionally substituted with one or two C_1-6alkyl groups),

with the proviso that in the 5 to 12-membered monocyclic or polycyclic heteroaryl group, a carbon atom on its ring is bonded with the carbon atom to which R³ is attached).

21. A pharmaceutical composition comprising a compound according to claim 8 or a reduced form thereof or a pharmaceutically acceptable salt thereof.

22. A pharmaceutical composition comprising a compound according to claim 9, or a reduced form thereof, or a pharmaceutically acceptable salt thereof, and a pharmaceutically acceptable excipient.

23. A method of treating and/or preventing a disease caused by or aggravated by oxidative stress or mitochondrial dysfunction, characterized by administering to a patient in need of the treatment and/or prevention a therapeutically effective amount of a compound according to claim 8 or a reduced form thereof or a pharmaceutically acceptable salt thereof.

12. (canceled)

14. (canceled)

15. (canceled)