6,7-dihydropyrazolo[1,5-α]pyrazin-4(5H)-one compounds and their use as negative allosteric modulators of mGluR2 receptors

A method for modulating metabotropic glutamate receptor 2 activity in a patient suffering from a disorder involving metabotropic glutamate receptor 2 activity, comprising administering to a patient in need thereof a compound of Formula (I):

• or a stereoisomeric form thereof, wherein:
• R1 is phenyl or 2-pyridinyl, each optionally substituted with one or more substituents each independently selected from the group consisting of halo, C1-4alkyl, monohalo-C1-4alkyl, polyhalo-C1-4alkyl, —C1-4alkyl-OH, —CN, —C1-4alkyl-O—C1-4alkyl, C3-7cycloalkyl, —O—C1-4alkyl, monohalo-C1-4alkyloxy, polyhalo-C1-4alkyloxy, SF5, C1-4alkylthio, monohalo-C1-4alkylthio and polyhalo-C1-4alkylthio;
• R2 is selected from the group consisting of C1-4alkyl;
• C3-7cycloalkyl;
• Het1;
• Aryl;
• Het2;
• and C1-4alkyl substituted with one or more substituents each independently selected from the group consisting of halo, C3-7cycloalkyl, Aryl, Het1 and Het2;
• wherein
• Aryl is phenyl optionally substituted with one or more substituents each independently selected from the group consisting of halo, C1-4alkyl, —C1-4alkyl-OH, monohalo-C1-4alkyl, polyhalo-C1-4alkyl, —CN, —O—C1-4alkyl, —OH, —C1-4alkyl-O—C1-4alkyl, —NR′R″, —NHC(O)C1-4alkyl, —C(O)NR′R″, —C(O)NH[C(O)C1-4alkyl], —S(O)2NR′R″, —S(O)2NH[C(O)C1-4alkyl] and —S(O)2—C1-4alkyl;
• Het1 is selected from the group consisting of oxetanyl, tetrahydrofuranyl and tetrahydropyranyl;
• Het2 is (a) a 6-membered aromatic heterocyclyl substituent selected from the group consisting of pyridinyl, pyrimidinyl, pyrazinyl and pyridazinyl, each of which may be optionally substituted with one or more substituents each independently selected from the group consisting of halo, C1-4alkyl, —C1-4alkyl-OH, monohalo-C1-4alkyl, polyhalo-C1-4alkyl, —CN, —O—C1-4alkyl, —OH, —C1-4alkyl-O—C1-4alkyl, —NR′R″, —NHC(O)C1-4alkyl, —C(O)NR′R″, —C(O)NH[C(O)C1-4alkyl], —S(O)2NR′R″, —S(O)2NH[C(O)C1-4alkyl] and —S(O)2—C1-4alkyl;
• or (b) a 5-membered aromatic heterocyclyl selected from the group consisting of thiazolyl, oxazolyl, 1H-pyrazolyl and 1H-imidazolyl, each of which may be optionally substituted with one or more substituents each independently selected from the group consisting of halo, C1-4alkyl, —C1-4alkyl-OH, monohalo-C1-4alkyl, polyhalo-C1-4alkyl, —CN, —O—C1-4alkyl, —OH, —C1-4alkyl-O—C1-4alkyl, —NR′R″, —NHC(O)C1-4alkyl, —C(O)NR′R″, —C(O)NH[C(O)C1-4alkyl], —S(O)2NR′R″, —S(O)2NH[C(O)C1-4alkyl] and —S(O)2—C1-4alkyl;
• R′ and R″ are each independently selected from the group consisting of hydrogen, C1-4alkyl and —C2-4alkyl-OH;
• R3 is selected from the group consisting of hydrogen and C1-4alkyl;
• and
• R4 is selected from the group consisting of hydrogen, C1-4alkyl, monohalo-C1-4alkyl, polyhalo-C1-4alkyl, —C1-4alkyl-O—C1-4alkyl and —C1-4alkyl-OH;
• or a N-oxide, or a pharmaceutically acceptable salt thereof.