Lactate enhancing compounds and uses thereof

A method of preventing or treating a disorder or a disease associated with an abnormally low intracerebral energy metabolism or in the central nervous system and/or a neurodegenerative disorder in a subject, said method comprising administering in a subject in need thereof a therapeutically effective amount of a compound of Formula (I),

• wherein R1, R2, R3, R4, R5 and R6 are independently selected from H, halogen, optionally substituted alkoxy, optionally substituted C1-C6 alkyl, optionally substituted amine, optionally substituted carboxylic acid or ester, nitro and nitrile;
• R7, R8, R9, R10 and R11 independently selected from H, halogen, optionally substituted alkoxy, optionally substituted C1-C6 alkyl, optionally substituted amine, optionally substituted carboxylic acid or ester, nitro and nitrile and a group of Formula (II):
• —(X)m—CR12R13R14 (II) wherein at least one group of R7, R8, R9, R10 and R11 is a group of Formula (II);
• X is selected from O, NR15, S, CH2 and hydrazine (—N—N—), m is an integer elected from 0 and 1 and R12, R13 and R14 are independently selected from H, OH, optionally substituted alkoxy, optionally substituted C1-C6 alkyl and halogen, wherein at least one of R12, R13 and R14 is F or Cl;
• Y is selected from —CR16R17— and —NR18—;
• R15 is selected from H, optionally substituted alkoxy and optionally substituted C1-C6 alkyl;
• R16 and R17 are independently selected from H, halogen, optionally substituted alkoxy, optionally substituted C1-C6 alkyl and optionally substituted aryl;
• R18 is independently selected from H or optionally substituted C1-C6 alkyl;
• or pharmaceutically acceptable salts, hydrates, solvates, or polymorphs, tautomers, geometrical isomers, optically active forms, enantiomeric mixtures thereof, and mixtures thereof.

A pharmaceutical composition comprising a compound of Formula (I)

• wherein R1, R2, R3, R4, R5 and R6 are independently selected from H, halogen, optionally substituted alkoxy, C1-C6 alkyl, optionally substituted by halogen C1-C6 alkoxy, amino, nitro, optionally substituted amine, optionally substituted carboxylic acid or ester, nitro and nitrile;
• R7, R1, R9, R10 and R11 independently selected from H, halogen, optionally substituted alkoxy, optionally substituted C1-C6 alkyl, optionally substituted amine, optionally substituted carboxylic acid or ester, nitro and nitrile and a group of Formula (II):
• —(X)m—CR12R13R14 (II) wherein at least one group of R7, R8, R9, R10 and R11 is a group of Formula (II);
• X is selected from O, NR15, S, CH2 and hydrazine (—N—N—), m is an integer elected from 0 and 1 and R12, R13 and R14 are independently selected from H, OH, optionally substituted alkoxy, optionally substituted C1-C6 alkyl and halogen, wherein at least one of R12, R13 and R14 is F or Cl;
• Y is selected from —CR16R17— and —NR18—;
• R15 is selected from H, optionally substituted alkoxy and optionally substituted C1-C6 alkyl;
• R16 and R17 are independently selected from H, halogen, optionally substituted alkoxy, optionally substituted C1-C6 alkyl and optionally substituted aryl;
• R18 is independently selected from H or optionally substituted C1-C6 alkyl;
• and pharmaceutically acceptable salts, hydrates, solvates, or polymorphs, tautomers, geometrical isomers, optically active forms, enantiomeric mixtures thereof, and mixtures thereof, and a pharmaceutically acceptable carrier, diluent or excipient thereof, with the proviso that it is not a compound selected from:
• N-[2-(trifluoromethyl)phenyl]isoquinolin-1-amine;
• N-[3-(trifluoromethyl)phenyl]isoquinolin-1-amine;
• and
• N-[4-(trifluoromethyl)phenyl]isoquinolin-1-amine.

A compound selected from:

• 6,7-dimethoxy-N-(4-(trifluoromethoxy)phenyl)isoquinolin-1-amine;
• 6,7-dimethoxy-N-(4-(trifluoromethyl)phenyl)isoquinolin-1-amine;
• N-(4-(trifluoromethoxy)phenyl)isoquinolin-1-amine;
• or
• 6,7-dimethoxy-1-(4-(trifluoromethoxy)benzyl)isoquinoline;
• or a tautomer, geometrical isomer, optically active form, enantiomeric mixture, pharmaceutically acceptable salt or mixture thereof.