Heteroaryl substituted 2-pyridinyl and 2-pyrimidinyl -6,7,8,9-tetrahydropyrimido[1,2-a] pyrimidin-4-one derivatives

A method of inhibiting the activity of glycogen synthase kinase 3-beta (GSK3-β), which comprises administering to a patient in need of said inhibition a therapeuticcally effective amount of a compound of formula (I) or a pharmaceutically acceptable salt thereof:

• wherein:
• X represents two hydrogen atoms, a sulfur atom, an oxygen atom or a C1-2 alkyl group and a hydrogen atom;
• Y represents a bond, an ethenylene group, an ethynylene group or a methylene group optionally substituted by one or two groups chosen from a C1-6 alkyl group, a hydroxy group or a C1-4 a hydroxy group;
• R1 represents a 2, 3 or 4-pyridine ring or a 2, 4 or 5-pyrimidine ring, the ring being optionally substituted by a C3-6 cycloalkyl group, a C1-4 alkyl group, a C1-4 alkoxy group, a benzyl group or a halogen atom;
• R2 represents a heterocyclic ring having 1-4 heteroatoms selected from an oxygen atom, a sulfur atom and a nitrogen atom and having 5-9 carbon atoms, of formula
• wherein A, B, C and D represent, each independently, a carbon atom or a nitrogen atom and W represent a saturated or unsaturated 5, 6 or 7 membered cyclic ring having from 3 to 7 carbon atoms and 2 to 0 heteroatoms selected from an oxygen atom, a sulfur atom or a nitrogen atom;
• the R2 group being optionally substituted on a carbon atom or, when possible, on a nitrogen atom by one or two atoms or groups chosen from a halogen atom, a C1-6 alkyl group, a hydroxy group, a C1-4 alkoxy group, a benzene ring, a pyridine ring or a —NR6R7 group;
• R3 represents a hydrogen atom, a C1-6 alkyl group, a hydroxy group, a C1-4 alkoxy group or a halogen atom;
• R4 represents a hydrogen atom, a C1-6 alkyl group, a C1-4 alkoxy group or a halogen atom;
• R5 represents a hydrogen atom, a C1-6 alkyl group, a C1-2 perhalogenated alkyl group, a C1-3 halogenated alkyl group or a halogen atom;
• R6 and R7 represent, each independently, a hydrogen atom, a C1-6 alkyl group, a benzyl group, a benzene ring or R6 and R7 represent together with the nitrogen atom, a pyrrolidine ring, a piperidine ring, a hexamethyleneimine ring, a morpholine ring or a piperazine ring, the ring being optionally substituted by one or two C1-6 alkyl group;
• when m equals 0, p equals 1, 2 or 3,
• when m equals 1, p equals 0, 1 or 2,
• when m equals 2, p equals 0 or 1;
• when m equals 3, p equals 0;
• and
• n represents 0 to 3;
• with the proviso that the compound of formula (I) is not:
• 9-[2-(1H-indol-3-yl)ethyl]-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrimido[1,2-α]pyrimidin-4-one;
• 9-[3-(1H-indol-3-yl)propyl]-2-pyridin-4-yl-6,7,8,9-tetrahydro-4H-pyrimido[1,2-α]pyrimidin-4-one;
• 1-[2-(1H-Indol-3-yl)ethyl]-7-pyridin-4-yl-2,3-dihydroimidazo[1,2-α]pyrimidin -5(1H)-one, or
• 1-[3-(1H-indol-3-yl)propyl]-7-pyridin-4-yl-2,3-dihydroimidazo[1,2-α]pyrimidin -5(1H)-one.