2-substituted-p-quinone derivatives for treatment of oxidative stress diseases

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;
• M and M′ are independently selected from the group consisting of hydrogen, —C(O)—R′, —C(O)—(C2-C6)-alkenyl, —C(O)—(C2-C6)-alkynyl, —C(0)-aryl, —C(O)—heterocyclyl, —C(O)O—R′, —C(O)NR′R″, —SO2OR′, —SO2(C1-C6)-alkyl, —SO2(C1-C6)-haloalkyl, —SO2-aryl, —SO2NR′R″, —P(O)(OR′)(OR″), and C-linked mono-or di-peptide, where R′ and R″ are independently of each other hydrogen or (C1-C6)-alkyl optionally substituted with one or more substituents independently selected from the group consisting of —OH, —NH2, —NH(C1-C4)-alkyl, —N((C1-C4)-alkyl)2, —C(O)OH, —C(O)O—(C1-C4)-alkyl, and halogen;
• R1 is (C1-C6)-alkyl, (C1-C6)-alkoxy, heterocyclyl, or aryl, where the heterocyclyl and the aryl are optionally substituted with one or more substituents independently selected from the group consisting of —OH, (C1-C6)-alkyl, (C1-C6)-alkoxy, hydroxyl-(C1-C6)alkyl-, alkoxy(C1-C6)-alkyl-, —NR10R10′, —(C1-C6)-alkyl —NR10R10′, —C(O)—(C1-C6)-alkyl, —C(O)—OH, —C(O)O—(C1-C6)-alkyl,—C(O)NR10R10′, —NR11C(O)R10, —NR11C(O)NR10R10—NR11(C(O)OR10, —SO2(C1-C6)-alkyl, —SO2 (C1-C6)-haloalkyl, —SO2-aryl, —SO2NR10R10′, CN, haloalkyl, and halogen;
• R2 is hydrogen, (C1-C6)-alkyl, or (C1-C6)-alkoxy;
• R3 is unsubstituted (C1-C6)-alkyl;
• R4 is hydrogen or (C1-C6)-alkyl;
• R5 is —C(O)NR6R7;
• R6 is hydrogen, (C1-C6)-alkyl, aryl, or heterocyclyl, where (C1-C6)-alkyl is optionally substituted with one or more substituents independently selected from the group consisting of:
• —OR11, —SR11, —CN, —F, —Cl, —Br, —I, —NR10R10′, (C3-C6)-cycloalkyl, aryl, heterocyclyl, —C(O)—R11, —C(O)—(C0-C6)-alkyl-aryl, —C(O)O—R11, —C(O)—O—(C0-C6)-alkyl-aryl, —C(O)N—R10R10′, C(O)NR11-(C0-C6)-alkyl-aryl, —NR11C(O)—R10, and —NR11C(O)—(C0-C6)-alkyl-aryl;
• wherein the aryl and heterocyclyl ring substituents may be further substituted with one or more groups independently selected from the group consisting of (C1-C6)-alkyl, halogen, (C1-C6) -haloalkyl, CN, oxo, hydroxy, (C1-C6)-alkoxy, —C(O)—(C1-C6) -alkyl, and —C(O)—O—(C1-C6)-alkyl;
• and where
• aryl and heterocyclyl are optionally substituted with (C1-C6)-alkyl, halogen, (C1-C6)-haloalkyl, CN, oxo, hydroxy, (C1-C6)-alkoxy, —C(O)—(C1-C6)-alkyl or —C(O)—O—(C1-C6)-alkyl;
• R7 is hydrogen or (C1-C6)-alkyl;
• or
• R6 and R7 together with the atom to which they are attached form a saturated or unsaturated 3-8 membered ring, optionally incorporating one, two, or three additional heteroatoms independently selected from the group consisting of N, O, and S atoms, and optionally substituted with oxo, —OH, —SH, —F, —Cl, —Br, —I, —NR11R11′, (C1-C6)-alkyl, (C1-C6)-alkoxy, (C1-C6)-thioalkyl, (C1-C6)-haloalkyl, hydroxy-(C1-C6)-alkyl, —C(O)—H, —C(O)—(C1-C6)-alkyl, —C(O)OH, or —C(O)O—(C1-C6)-alkyl;
• R10 and R10′ are independently selected from the group consisting of H, (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 a saturated or unsaturated 3-8 membered ring, optionally incorporating one, two, or three additional heteroatoms independently selected from the group consisting of N, O, and S atoms, and optionally substituted with one or more substituents independently selected from the group consisting of oxo, —OH, —F,—Cl, —Br, —I, —NR11R11′, (C1 C6)-alkyl, (C1-C6)-alkoxy, (C1-C6)-haloalkyl, hydroxy -(C1-C6)-alkyl-, —C(O)—H, —C(O )—(C1-C6)-alkyl, —C(O)OH, and —C(O)O—(C1-C6)-alkyl;
• R11 and R11′ are independently selected from the group consisting of hydrogen and (C1-C6)-alkyl;
• and
• A is (C1-C4)-alkylene, (C2-C4)-alkenylene, or (C2-C4)-alkynylene;
• or a salt, a stereoisomer, or a mixture of stereoisomers thereof.