Methods for treating central nervous system disorders using vdac inhibitors

A method for treating a CNS-associated disorder selected from the group consisting of psychotic disorder, mood disorder and neurodegenerative disease, the method comprising the step of administering to a subject in need thereof at least one compound of the general formula (I):

• wherein:
• A is carbon (C) or nitrogen (N);
• R3 is absent, a hydrogen, an unsubstituted or substituted amide, or a heteroalkyl comprising 3-12 atoms (apart from hydrogen atoms), wherein at least one atom is a nitrogen, sulfur or oxygen atom, wherein when A is nitrogen (N), R3 is absent;
• L1 is absent or is an amino linking group —NR4—, wherein R4 is hydrogen, a C1-5-alkyl, a C1-5-alkylene or a substituted alkyl —CH2R, wherein R is a functional group selected from the group consisting of hydrogen, halo, haloalkyl, cyano, nitro, hydroxyl, alkyl, alkenyl, aryl, alkoxyl, aryloxyl, aralkoxyl, alkylcarbamido, arylcarbamido, amino, alkylamino, arylamino, dialkylamino, diarylamino, arylalkylamino, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, alkylcarbonyloxy, arylcarbonyloxy, carboxyl, alkoxycarbonyl, aryloxycarbonyl, sulfo, alkylsulfonylamido, alkylsulfonyl, arylsulfonyl, alkylsulfinyl, arylsulfinyl and heteroaryl;
• R1 is a phenyl, which is optionally substituted with one or more of Z;
• Z is independently at each occurrence a functional group selected from the group consisting of, hydrogen, halo, haloalkyl, haloalkoxy, perhaloalkoxy or C1-2-perfluoroalkoxy, cyano, nitro, hydroxyl, alkyl, alkenyl, aryl, alkoxyl, aryloxyl, aralkoxyl, alkylcarbamido, arylcarbamido, amino, alkylamino, arylamino, dialkylamino, diarylamino, arylalkylamino, aminocarbonyl, alkylaminocarbonyl, arylaminocarbonyl, alkylcarbonyloxy, arylcarbonyloxy, carboxyl, alkoxycarbonyl, aryloxycarbonyl, sulfo, alkylsulfonylamido, alkylsulfonyl, arylsulfonyl, alkylsulfinyl, arylsulfinyl and heteroaryl;
• L2 is a linking group such that:
• when A is nitrogen (N), L2 is selected from the group consisting of butanamidylene, N-methylbutanamidylene, N,N-dimethylbutanamidylene, 4-hydroxybutanamidylene, 4-oxobutanamidylene, 4-hydroxy-N-methylbutanamidylene and 4-oxo-N-methylbutanamidylene, wherein the carbon (C) in third position of the butanamide moiety is bonded to the nitrogen (N) of the piperazine ring and the nitrogen (N) of the butanamide moiety is bonded to R2;
• or L2 is selected from the group consisting of 2-pyrrolidone, pyrrolidine-2,5-dione, 5-thioxo-2-pyrrolidone or 5-methoxy-2-pyrrolidone, wherein a carbon (C) of the pyrrolidine moiety is bonded to the nitrogen (N) of the piperazine ring and the nitrogen (N) of the pyrrolidine moiety is bonded to R2;
• and
• when A is carbon (C), L2 is selected from the group consisting of C1-4alkylene or a group consisting of 4-10 atoms, apart from hydrogen atoms, optionally forming a ring, wherein at least one of the atoms is nitrogen, said nitrogen forming part of an amide group;
• R2 is a phenyl or a naphthyl, optionally substituted with halogen;
• or an enantiomer, diastereomer, mixture or salt thereof.