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

A compound of Formula III:

• where R is selected from the group consisting of:
• where the * indicates the point of attachment of R to the remainder of the molecule;
• A is (C1-C4)-alkylene, (C2-C4)-alkenylene, or (C2-C4)-alkynylene;
• B3 is C(O) or S(O)2;
• R1 is (C1-C6)-alkyl;
• R2 is (C1-C6)-alkyl;
• R3 is (C1-C6)-alkyl;
• R35 and R36 are independently selected from the group consisting of hydrogen, hydroxy, alkoxy, (C1-C40)-alkyl, (C2-C40)-alkenyl, (C2-C40)-alkynyl, aryl and heterocyclyl;
• where the alkyl, alkenyl and alkynyl groups may independently optionally be substituted with one or more substituents selected from the group consisting of:
• —OR10, —SR10, —CN, —F, —Cl, —Br, —I,—NR10aR10b, 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—R11aR11b, —C(O)—NH—C0—C6-alkyl-aryl, —NH—C(O)—R11, and —NH—C(O)—C0-C6-alkyl-aryl;
• and
• where the aryl, heteroaryl and heterocyclyl rings may independently be further substituted with one or more substituents selected from the group consisting of:
• (C1-C6)-alkyl, (C1-C6)-haloalkyl, —CN, —F, —Cl, —Br, —I, —NR10aR10b, 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 replaced by a heteroatom selected from the group consisting of O, N and S;
• or
• R35 and R36 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 selected from the group consisting of:
• oxo, —OR10, —SR10, —CN, —F, —Cl, —Br, —I, —NR10aR10b, (C1-C6)-alkyl, (C1-C6)-haloalkyl;
• —(C1-C6)-alkyl-hydroxy, —C(O)—H, —C(O)—(C1-C6)-alkyl , —C(O)—OH, and —C(O)—O—(C1-C6)-alkyl;
• R10, R10a, and R10b 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;
• R11, R11a, and R11b are independently selected from the group consisting of hydrogen and (C1-C6)-alkyl;
• or R11a and R11b 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, —OR10, —SR10, —CN, —F, —Cl, —Br, —I, —NR10aR10b, (C1-C6) alkyl, (C1-C6)-haloalkyl;
• —(C1-C6)-alkyl- hydroxy, —C(O)—H, —C(O)—(C1-C6)-alkyl , —C(O)—OH, or —C(O)—O—(C1-C6)-alkyl;
• 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)NR12aR12b, —SO2OR12, —SO2-(C1-C6)-alkyl, —SO2—(C1-C6)- haloalkyl;
• —SO2-aryl, —SO2—NR12aR12b, —P(O)(OR12a)(OR12b), and C-linked mono or di-peptide, where R12, R12a, and R12b are independently hydrogen or (C1-C6)-alkyl optionally substituted with —OH, —NH2, —NH((C1-C6)-alkyl), —N ((C1-C4)-alkyl)2, —C(O)—OH, —C(O)—O—(C1-C4)-alkyl or halogen;
• with the proviso that the compound is not:
• N-(4-hydroxy-3,5-dimethylphenyl)-5-(2,4,5-trimethyl-3,6-dioxocyclohexa-1,4-dienyl)pentanamide or 5-(2,5-dihydroxy-3,4,6-trimethylphenyl)-N-(4-hydroxy-3,5-dimethylphenyl)pentanamide;
• or a salt, a stereoisomer, or a mixture of stereoisomers thereof.