| 摘要 |
Methods of treating or suppressing mitochondrial diseases, such as Friedreich's ataxia (FRDA), Leber's Hereditary Optic Neuropathy (LHON), mitochondrial myopathy, encephalopathy, lactacidosis, and stroke (MELAS), Kearns-Sayre Syndrome (KSS), are disclosed, as well as compounds useful in the methods of the invention, such as 4-(p-quinolyl)-2-hydroxybutanamide derivatives. Methods and compounds useful in treating other disorders such as amyotrophic lateral sclerosis (ALS), Huntington's disease, Parkinson's disease, and pervasive developmental disorders such as autism are also disclosed. Energy biomarkers useful in assessing the metabolic state of a subject and the efficacy of treatment are also disclosed. Methods of modulating, normalizing, or enhancing energy biomarkers, as well as compounds useful for such methods, are also disclosed. |
| 主权项 |
1. 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; R1, R2, and R3 are independently selected from the group consisting of hydrogen and C1-C6-alkyl; R4 is C1-C6-alkyl; R5 and R6 together with the atom to which they are attached form a saturated or unsaturated 3-8 membered ring, optionally incorporating 1, 2, or 3 additional atoms individually selected from the group consisting of N, O, and S atoms, optionally substituted with oxo, —OR10, —SR10, —CN, —F, —Cl, —Br, —I, —NR10R10′, C1-C6-alkyl, C1-C6-haloalkyl, hydroxy-C1-C6-alkyl, —C(O)—H, —C(O)—C1-C6-alkyl, —C(O)-aryl, —C(O)—OH, or —C(O)—O—C1-C6-alkyl; 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, alkyl, —C(O)-aryl and —C(O)—C1-C6-alkyl-aryl; and M and M′ are independently selected from the group consisting of hydrogen, —C(O)—R12, —C(O)—C2-C6-alkenyl, —C(O)—C2-C6-alkynyl, —C(O)-aryl, —C(O)-heteroaryl, —C(O)O—R12, —C(O)NR12R12, —SO2OR12, —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. |
