1,2,4-triazolo[4,3-a]pyridine derivatives and their use as positive allosteric modulators of mGluR2 receptors

A compound having the formula (I)

• or a stereochemically isomeric form thereof, wherein
• the bond drawn into the ring indicates that the bond may be attached to any carbon ring atom;
• R1 is selected from the group consisting of hydrogen;
• C1-6alkyl;
• (C1-3alkyloxy)-C1-3alkyl;
• [(C1-3alkyloxy)-C1-3alkyloxy]C1-3alkyl;
• C1-3alkyl substituted with one or more independently selected halo substituents;
• unsubstituted benzyl;
• benzyl substituted with one or more substituents each independently selected from the group consisting of halo, C1-3alkyl, (C1-3alkyloxy)C1-3alkyl, C1-3alkyloxy, hydroxyC1-3alkyl, cyano, hydroxyl, amino, (C═O)R′, (C═O)OR′, (C═O)NR′R″, mono- or di-(C1-3alkyl)amino, morpholinyl, (C3-7cycloalkyl)C1-3alkyloxy, trifluoromethyl and trifluoromethoxy, wherein R′ and R″ are independently selected from hydrogen and C1-6alkyl;
• (benzyloxy)C1-3alkyl;
• unsubstituted C3-7cycloalkyl;
• C3-7cycloalkyl substituted with one or more independently selected C1-3alkyl substituted with one or more independently selected halo substituents;
• (C3-7cycloalkyl)C1-3alkyl;
• 4-(2,3,4,5-tetrahydro-benzo[f][1,4]oxazepine)methyl;
• Het1;
• Het1C1-3alkyl;
• Het2;
• and Het2C1-3alkyl;
• R2 is selected from the group consisting of cyano;
• halo;
• C1-3alkyl substituted with one or more independently selected halo substituents;
• C1-3alkyloxy substituted with one or more independently selected halo substituents;
• C1-3alkyl;
• C3-7cycloalkyl;
• and (C3-7cycloalkyl)C1-3alkyl;
• forms a radical selected from (a), (b), (c), (d) and (e):
• wherein
• the bond drawn into (a) indicates that R4 may be attached to any of carbon ring atoms 2 and 3;
• each R3 is independently selected from the group consisting of hydrogen;
• unsubstituted C1-6alkyl;
• C1-6alkyl substituted with one or more substituents independently selected from the group consisting of halo, hydroxy, C1-3alkoxy and trifluoromethyl;
• unsubstituted C3-7cycloalkyl;
• C3-7cycloalkyl substituted with one or more substituents independently selected from the group consisting of halo, C1-3alkyl, hydroxy, C1-3alkoxy and trifluoromethyl;
• C3-7cycloalkylC1-3alkyl;
• unsubstituted phenyl;
• phenyl substituted with one or more substituents independently selected from the group consisting of halo, C1-3alkyl, C1-3alkoxy and trifluoromethyl;
• Het3;
• and Het3C1-3alkyl;
• or
• each R3 is independently selected from a cyclic radical of formula (f)
• wherein R8 is selected from hydrogen, C1-3alkyl, C1-3alkyloxy and hydroxyC1-3alkyl;
• q is 1 or 2;
• X is selected from O, CH2 and CR9(OH), wherein R9 is selected from hydrogen, C1-3alkyl and C3-7cycloalkyl;
• or
• X is a cyclic radical of formula (g)
• wherein r and s are independently selected from 0, 1 and 2, provided that r+s≧2;
• each R4, R6 and R7 are each independently selected from C1-3alkyl and C1-3alkyl substituted with one or more independently selected halo substituents;
• each R5 is independently selected from the group consisting of hydrogen, C1-3alkyl, and C1-3alkyl substituted with one or more independently selected halo substituents;
• n, m and p are each independently selected from 0, 1 and 2;
• v is 0 or 1;
• t and u are each independently selected from 1 and 2;
• W is selected from N and C10;
• wherein R10 is selected from hydrogen, halo and trifluoromethyl;
• each Het1 is a saturated heterocyclic radical selected from pyrrolidinyl;
• piperidinyl;
• piperazinyl;
• and morpholinyl;
• each of which may be optionally substituted with one or more each independently selected from the group consisting of C1-6alkyl;
• mono-, di- and tri-haloC1-3alkyl;
• unsubstituted phenyl;
• and phenyl substituted with 1, 2 or 3 substituents independently selected from the group consisting of halo, trifluoromethyl, and trifluoromethoxy;
• each Het2 is pyridyl or pyrimidinyl;
• and
• each Het3 is a heterocycle selected from the group consisting of tetrahydropyran, pyridyl;
• and pyrimidinyl;
• each of them being optionally substituted with one or more substituents each independently selected from the group consisting of halo, C1-3alkyl, C1-3alkoxy and trifluoromethyl;
• and
• halo is selected from fluoro, chloro, bromo and iodo;
• or a pharmaceutically acceptable salt thereof.