AMIDE DERIVATIVES AS GLYCOGEN SYNTHASE KINASE 3-BETA INHIBITORS

This invention concerns a compound of formula (I' ),a N-oxide, a pharmaceutically acceptable addition salt, a quaternary amine and a stereochemically isomeric form thereof, wherein ring A represents a 6-membered heterocycle; R1 is hydrogen; aryl; formyl; C1-6alkylcarbonyl; optionally substituted C1-6alkyl; C1-6alkyloxycarbonyl; optionally substituted C1-6alkyloxyC1-6alkylcarbonyl; X is a direct bond or a linker atom or group; Z is O or S; R2 is hydrogen, C1-10alkyl, C2-10alkenyl, C2-10alkynyl, a carbocycle or a heterocycle, each of said groups may optionally be substituted; R3 is hydrogen; hydroxy; halo; optionally substituted C1-6alkyl or C2-6alkenyl or C2-6alkynyl; C1-6alkyloxy; C1-6alkylthio; C1-6alkyloxycarbonyl; C1-6alkylcarbonyloxy; carboxyl; cyano; nitro; amino; mono- or di(C1-6alkyl)amino; polyhaloC1-6alkyl; polyhaloC1-6alkyloxy; polyhaloC1-6alkylthio; R21; R21-C1-6alkyl; R21-O-; R21-S-; R21-C(=O)-; R21-S(=O)p-; R7-S(=O)p-; R7-S(=O)p-NH-; R21-S(=O)p-NH-; R7-C(=O)-; -NHC(=O)H;-C(=O)NHNH2; R7-C(=O)-NH-; R21-C(=O)-NH-; -C(=NH)R7; -C(=NH)R21 ; R4a or R4b each independently represent hydrogen, R8, -Y1-NR9-Y2-NR10R11, -Y1-NR9-Y1-R8, -Y1-NR9R10; provided that -X-R2 and/or R3 is other than hydrogen; their use, pharmaceutical compositions comprising them and processes for their preparation. La invencion se refiere a compuestos de formula (I??), ver formula (I). Un N-oxido, una sal de adicion farmaceuticamente aceptable, una amina cuaternaria y una forma estereoquimicamente isomerica de las mismas, en donde el anillo A representa un heterociclo de 6 miembros; R1 es hidrogeno; arilo; formilo; alquilcarbonilo de C1-6 alquilo de C1-6opcionalmete sustituido; alquilocarbonilo de C1-6; alquiloxi de C1-6 opcionalmente sustituido alquyilcarbonilo de C1-6; X es un enlace directo o un atomo o grupo enlazador; Z es O o S; R2 es hidrogeno, alquilo de C1-10 alquelino de C2-10, alquilino de C2-10, un carbociclo o un heterociclo, cada uno de dichos grupos puede estar opcionalmente sustituido; R3 es hidrogeno; hidroxi; halo; alquilo de C1-6 opcionalmente sustituido o alquelino de C2-6 o alquilino de C2-6; alquiloxi de C1-6; alquilito de C1-6; alquiloxicarbonilo de C1-6; alquilocaboxinoli de C1-6; carboxilo; ciano; nitro; amino; mono-o di(alquilo de C1-6) amino; polihaloalquilo de C1-6; polihalquiloxi de C1-6; polihalquilito de C1-6; R21; R21-alquilo de C1-6, R21-S-; R21-S(=O)-; R21-S -(=O)p-;R7 -S(=O)p-; R7-S (=O)p-NH-; R21-S (=O)p-NH-; Rr-C (=O)-; -NHC(=O); -C(=O) NHNH2; R