4-(p-quinonyl)-2-hydroxybutanamide derivatives for treatment of mitochondrial diseases

A method of treating or suppressing a mitochondrial disorder or mitochondrial dysfunction, wherein the disorder or dysfunction is selected from the group consisting of Autistic Disorder, Friedreich's Ataxia, Huntington's Disease, Leber's Hereditary Optic Neuropathy (LHON), and Parkinson's disease, by administering to a subject a therapeutically effective amount of one or more compounds of Formula Ia:

• where
• R1, R2, and R3 are independently selected from hydrogen and C1-C6-alkyl;
• R4 is C1-C6-alkyl;
• R5 and R6 are independently selected from hydrogen, hydroxy, alkoxy, C1-C40-alkyl, C1-C40-alkenyl, C1-C40-alkynyl, and aryl;
• where the alkyl, alkenyl, alkynyl, or aryl groups may optionally be substituted with
• —OR10, —S(O)0-2R10, —CN, —F, —Cl, —Br, —I, —NR10R10′, oxo, C3-C6-cycloalkyl, aryl, aryl-C1-C6-alkyl, heteroaryl, heterocyclyl, —C(O)—R11, —C(O)—C0-C6-alkyl-aryl, —C(O)—O—R11, —C(O)—O—C0-C6-alkyl-aryl, —C(O)—N—R11R11, —C(O)—N—C0-C6-alkyl-aryl, —N—C(O)—R11, —N—C(O)—C0-C6-alkyl-aryl;
• where the aryl, heteroaryl and heterocyclyl ring substituents may be further substituted with C1-C6-alkyl, C1-C6-haloalkyl, oxo, hydroxy, C1-C6-alkoxy, —C(O)—C1-C6-alkyl and —C(O)—O—C1-C6-alkyl;
• and where one of the carbons of the alkyl, alkenyl, or alkynyl groups may be substituted with a heteroatom selected from O, N or S;
• R10 and R10′ are independently selected from the group consisting of hydrogen, C1-C6-alkyl, C1-C6-haloalkyl, aryl, aryl-C1-C6-alkyl, heteroaryl, heterocyclyl, —C(O)—H, —C(O)—C1-C6-alkyl, —C(O)-aryl and —C(O)—C1-C6-alkyl-aryl;
• and
• R11 and R11′ are selected from hydrogen and C1-C6-alkyl;
• or a salt, a stereoisomer, or a mixture of stereoisomers thereof.

A method of treating or suppressing a mitochondrial disorder or mitochondrial dysfunction, wherein the disorder or dysfunction is selected from the group consisting of Autistic Disorder, Friedreich's Ataxia, Huntington's Disease, Leber's Hereditary Optic Neuropathy (LHON), and Parkinson's disease, the method comprising administering to a subject a therapeutically effective amount of one or more compounds of Formula Ib:

• wherein R1, R2, and R3 are independently selected from hydrogen and C1-C6-alkyl;
• R4 is C1-C6-alkyl;
• R5 and R6 are independently selected from hydrogen, hydroxy, alkoxy, C1-C40-alkyl, C1-C40-alkenyl, C1-C40-alkynyl, and aryl;
• where the alkyl, alkenyl, alkynyl, or aryl groups may optionally be substituted with
• —OR10, —S(O)0-2R10, —CN, —F, —Cl, —Br, —I, —NR10R10′, oxo, C3-C6-cycloalkyl, aryl, aryl-C1-C6-alkyl, heteroaryl, heterocyclyl, —C(O)—R11, —C(O)—C0-C6-alkyl-aryl, —C(O)—O—R11, —C(O)—O—C0-C6-alkyl-aryl, —C(O)—N—R11R11, —C(O)—N—C0-C6-alkyl-aryl, —N—C(O)—R11, —N—C(O)—C0-C6-alkyl-aryl;
• where the aryl, heteroaryl and heterocyclyl ring substituents may be further substituted with C1-C6-alkyl, C1-C6-haloalkyl, oxo, hydroxy, C1-C6-alkoxy, —C(O)—C1-C6-alkyl and —C(O)—O—C1-C6-alkyl;
• and where one of the carbons of the alkyl, alkenyl, or alkynyl groups may be substituted with a heteroatom selected from O, N or S;
• R10 and R10′ are independently selected from the group consisting of hydrogen, C1-C6-alkyl, C1-C6-haloalkyl, aryl, aryl-C1-C6-alkyl, heteroaryl, heterocyclyl, —C(O)—H, —C(O)—C1-C6-alkyl, —C(O)-aryl and —C(O)—C1-C6-alkyl-aryl;
• or
• R10 and R10′ together with the atom to which they are attached form an optionally substituted saturated or unsaturated 3-8 membered ring, optionally incorporating 1, 2, or 3 N, O, or S atoms;
• R11 and R11′ are selected from hydrogen and C1-C6-alkyl;
• and
• M and M′ are independently selected from hydrogen, —C(O)—R12, —C(O)—C1-C6-alkenyl, —C(O)—C1-C6-alkynyl, —C(O)-aryl;
• —C(O)-heteroaryl, —C(O)O—R12, —C(O)NR12R12, —SO2—C1-C6-alkyl, —SO2-haloC1-C6-alkyl;
• —SO2-aryl, —SO2—NR12R12, —P(O)(OR12)(OR12), and C-linked mono or di-peptide, where R12 is hydrogen or C1-C6-alkyl optionally substituted with —OH, —NH2, —NH(C1-C4alkyl), —N(C1-C4alkyl)2, —C(O)—OH, —C(O)—O—C1-C4-alkyl or halogen;
• or a salt, a stereoisomer, or a mixture of stereoisomers thereof.