TRIAZOLOPYRIMIDINE DERIVATIVES AS GLYCOGEN SYNTHASE KINASE 3 INHIBITORS

摘要

This invention concerns compounds of formula (I) a N-oxide, a pharmaceutically acceptable addition salt, a quaternary amine and a stereochernically isomeric form thereof, wherein ring A represents phenyl, pyridyl, pyrimidinyl, pyridazinyl or pyrazinyl; R<1> represents hydrogen; aryl; formyl; C1-6 alkylcarbonyl; C1-6 a]kyl; C1-6 alkyloxycarbonyl; C1-6 alkyl substituted with formyl, C1-6alkylcarbonyl, C1-6alkyloxycarbonyl, C1-6alkylcarbonytoxy; or optionally substituted C1-6 alkyloxyCl-6alkylcarbonyl; X1 represents a direct bond; -(CH2)n3- or -(CH2)n4-X1a-X1b-; R<2> represents optionally substituted C3-7CYCloalkyl; phenyl; a 4, 5, 6- or 7-membered monocyclic heterocycle containing at least one heteroatorn selected from 0, S or N; benzoxazolyl or a radical of formula (a-1); X2 represents a direct bond; -NR<1>-NR<1>-(CH2)N3 -; -0-; -0-(CH2)n3-; -C(=O)-; -C(=O)- (CH2)n3-; -C(=O)-NR<5>-(CH2)n3-; -C(=S)-; -S-; -S(=O)n1-; -(CH2)n3-; -(CH2)n4-X1a-X1b-; -X1a.-X1b-(CH2)n4-; -S(=O)n1-NR<5>-(CH2)n3-NR<5>_ or -S(=O)n1,-NR<5> -(CH2)n3-; R<3> represents an optionally substituted 5-or 6-membered monocyclic heterocycle containing at least one heteroatom selected from 0, S or N, or a 9-or 10-membered bicyclic heterocycle containing at least one heteroatom selected from 0, S or N; R<4> represents hydrogen; halo; hydroxy; optionally substituted C1-4alkyl; optionally substituted C2-4alkenyl or C2-4alkynyl; polyhaloC1-3alkyl; optionally substituted C1-4alkyloxy; polyhaloC1-3alkyloxy; C1-4alkylthio; polyhaloC1-3alkylthio; C1-4alkyloxycarbonyl; C1-4alkylcarbonyloxy; C1-4alkylcarbonyl; polyhaloC1-4alkylcarbonyl; nitro; cyano; carboxyl; NR<9>R<10>; C(=O)NR<9>R<10>;-NR<5_>C(=O)-NR<9>R<10>; -NR<5>-C(=O)-R<5>; -S(=O) n1,-R<11> -NR<5>-S(=O)n1,-R<11> -S-CN; -NR<5> -CN; their use, pharmaceutical compositions comprising them and processes for their preparation.