Imidazopyridin-2-one derivatives

摘要

The present invention is directed to imidazopyridin-2-one derivatives which are potentiators of metabotropic glutamate receptors, particularly the mGluR2 receptor, and which are useful in the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which metabotropic glutamate receptors are involved. The invention is also directed to pharmaceutical compositions comprising these compounds and the use of these compounds and compositions in the prevention or treatment of such diseases in which metabotropic glutamate receptors are involved.

主权项

1. A compound according to Formula Iaor a pharmaceutically acceptable salt thereof, wherein:
X1 is selected from the group consisting of: C1-8 alkyl, C2-8 alkenyl, C2-8 alkynyl, C3-6 cycloalkyl and C3-6cycloalkylC1-4alkyl, any of which may bear up to 5 halogen substituents; R3 is selected from the group consisting of: halogen, OH, oxo, CN, CF3, R5, OR4, SR5, SO2R5, COCH2SO2R5, SO2N(R4)2, COR5, CO2R4, CON(R4)2, N(R4)2, NR4COR5, NR4CON(R4)2, NR4CO2R4, NR4SO2R5, —C1-4alkyl-N(R4)2, —C1-4alkyl-NR4COR5 and —C1-4alkyl-NR4CO2R4; each R4 independently represents H, C1-6alkyl, C3-10cycloalkyl, C3-10cycloalkylC1-4alkyl, C3-10cycloalkenyl or C3-10cycloalkenylC1-4alkyl, any of which except H optionally bear up to 3 halogen atoms or with OH, CN, CF3, OCF3, C1-4alkoxy, C1-4alkyl-C(O)—O—, C1-4alkyl-C(O)—, amino, C1-4alkylamino and di(C1-4alkyl)amino, or R4 represents phenyl, benzyl, phenylethyl, 5- or 6-membered monocyclic heteroaryl optionally bridged with —(CH2)p—, or a 9- or 10-membered bicyclic heteroaryl optionally bridged with —(CH2)p—, any of which optionally bear up to 3 substituents independently selected from halogen, OH, CN, CF3, OCF3, C1-4alkyl, C3-6cycloalkyl, phenyl, C1-4alkoxy, amino, C1-4alkylamino, di(C1-4alkyl)amino, a 5- or 6-membered monocyclic heteroaryl optionally bridge with methylene and optionally substituted with one or two methyl groups, and Het, optionally substituted with 1 to 3 substituents selected from oxo and methyl, or R4 represents Het, optionally bridged with —(CH2)p— and said Het optionally bearing up to 3 substituents independently selected from halogen, OH, oxo, CN, CF3, OCF3, C1-4alkyl, C3-6cycloalkyl, phenyl, benzyl, a 5- or 6-membered monocyclic heteroaryl optionally bridged with methylene and substituted with one or two methyl groups, C1-4alkoxy, C1-4alkyl-O—C(O)—, C1-4alkyl-C(O)—, acetyl, amino, C1-4alkylamino, di(C1-4alkyl)amino and Het, optionally substituted with 1 to 3 substituents selected from oxo and methyl; each p is independently 1, 2, 3 or 4; and R5 has the same definition as R4 except that R5 is not H.