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; R¹ represents hydrogen; aryl; formyl; C_1-6 alkylcarbonyl; C_1-6 a]kyl; C_1-6 alkyloxycarbonyl; C_1-6 alkyl substituted with formyl, C_1-6alkylcarbonyl, C_1-6alkyloxycarbonyl, C_1-6alkylcarbonytoxy; or optionally substituted C_1-6 alkyloxyCl-6alkylcarbonyl; X₁ represents a direct bond; -(CH₂)_n3- or -(CH₂)_n4-X_1a-X_1b-; R² represents optionally substituted C_3-7CYCloalkyl; 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; -NR¹-NR¹-(CH₂)_N3 -; -0-; -0-(CH₂)_n3-; -C(=O)-; -C(=O)- (CH₂)_n3-; -C(=O)-NR⁵-(CH₂)_n3-; -C(=S)-; -S-; -S(=O)_n1-; -(CH₂)_n3-; -(CH₂)_n4-X_1a-X_1b-; -X_1a.-X_1b-(CH₂)_n4-; -S(=O)_n1-NR⁵-(CH₂)_n3-NR⁵_ or -S(=O)_n1,-NR⁵ -(CH₂)_n3-; R³ 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; R⁴ represents hydrogen; halo; hydroxy; optionally substituted C_1-4alkyl; optionally substituted C_2-4alkenyl or C_2-4alkynyl; polyhaloC_1-3alkyl; optionally substituted C_1-4alkyloxy; polyhaloC_1-3alkyloxy; C_1-4alkylthio; polyhaloC_1-3alkylthio; C_1-4alkyloxycarbonyl; C_1-4alkylcarbonyloxy; C_1-4alkylcarbonyl; polyhaloC_1-4alkylcarbonyl; nitro; cyano; carboxyl; NR⁹R¹⁰; C(=O)NR⁹R¹⁰;-NR^5_C(=O)-NR⁹R¹⁰; -NR⁵-C(=O)-R⁵; -S(=O) _n1,-R¹¹ -NR⁵-S(=O)_n1,-R¹¹ -S-CN; -NR⁵ -CN; their use, pharmaceutical compositions comprising them and processes for their preparation.