Napthoquinone derivatives as inhibitors of tau aggregation for the treatment of alzheimer's and related neurodegenerative disorders

A method of treatment of a neurodegenerative disease or clinical dementia, either being associated with tau protein aggregation, which method comprises administering to a subject a therapeutically effective amount of a compound, wherein the compound is selected from

• a compound of formula II:
• wherein
• R1A is —OMe, —OC(═O)Me, —COOH, —COOMe, —SO3H, —SO3M, or —SO3Me;
• R2A is —H, unsubstituted C1-7 alkyl, C1-7 haloalkyl, C1-7 hydroxyalkyl, C1-7 aminoalkyl, C1-7 carboxyalkyl, —OH, C1-7 alkoxy, acyloxy, —COOH, ester, —SO3H, —SO3M, sulfonate, C1-7 alkylsulfonate, or a short chain alkyl group;
• R3, R4, R5, and R6 are independently —H, —OH, C1-7 alkyl, C1-7 alkoxy or acyloxy;
• and,
• M denotes a cation or cations of charge or cumulative charge to counter the charge on the —SO3— group;
• or
• a compound of formula III:
• or a compound of formula IV:
• wherein for formula III or IV:
• either
• (A) R1A is unsubstituted C1-7 alkyl, C1-7 haloalkyl, C1-7 hydroxyalkyl, C1-7 aminoalkyl, C1-7 carboxyalkyl, —OH, C1-7 alkoxy, acyloxy, —COOH, ester, —SO3H, —SO3M, sulfonate, C1-7 alkylsulfonate, or a short chain alkyl group;
• and
• R2A is —H, unsubstituted C1-7 alkyl, C1-7 haloalkyl, C1-7 hydroxyalkyl, C1-7 aminoalkyl, C1-7carboxyalkyl, —OH, C1-7 alkoxy, acyloxy, —COOH, ester, —SO3H, —SO3M, sulfonate, C1-7 alkylsulfonate, or a short chain alkyl group;
• or
• (B) R1A is —H, unsubstituted C1-7 alkyl, C1-7 haloalkyl, C1-7 hydroxyalkyl, C1-7 aminoalkyl, C1-7 carboxyalkyl, —OH, C1-7 alkoxy, acyloxy, —COOH, ester, —SO3H, —SO3M, sulfonate, C1-7 alkylsulfonate, or a short chain alkyl group;
• and
• R2A is unsubstituted C1-7 alkyl, C1-7 haloalkyl, C1-7 hydroxyalkyl, C1-7 aminoalkyl, C1-7carboxyalkyl, —OH, C1-7 alkoxy, acyloxy, —COOH, ester, —SO3H, —SO3M, sulfonate, C1-7 alkylsulfonate, or a short chain alkyl group;
• R1B, if present, is —H, unsubstituted C1-7alkyl, C1-7haloalkyl, C1-7hydroxyalkyl, C1-7aminoalkyl, C1-7carboxyalkyl, —OH, C1-7alkoxy, acyloxy, —COOH, ester, —SO3H, —SO3M, sulfonate, C1-7alkylsulfonate, or a short chain alkyl group;
• R2B, if present, is —H, unsubstituted C1-7alkyl, C1-7haloalkyl, C1-7hydroxyalkyl, C1-7aminoalkyl, C1-7carboxyalkyl, —OH, C1-7alkoxy, acyloxy, —COOH, ester, —SO3H, —SO3M, sulfonate, C1-7alkylsulfonate, or a short chain alkyl group;
• R3, R4, R5, and R6 is independently —H, —OH, C1-7alkyl, C1-7alkoxy, or acyloxy;
• and,
• R7 and R8 is independently —H, C1-7alkyl, acyl, —SO3H, —SO3M, or sulfonate;
• M denotes a cation or cations of charge or cumulative charge to counter the charge on the —SO3 group;
• and a pharmaceutically acceptable salt thereof, or a therapeutic composition comprising the same, such as to inhibit the aggregation of the protein associated with said disease or dementia.