| 摘要 |
The present invention relates to novel compounds, in particular novel pyridinone derivatives according to Formula (I);
wherein all radicals are defined in the application and claims. The compounds according to the invention are positive allosteric modulators of metabotropic receptors-subtype 2 (“mGluR2”) which are useful for the treatment or prevention of neurological and psychiatric disorders associated with glutamate dysfunction and diseases in which the mGluR2 subtype of metabotropic receptors is involved. In particular, such diseases are central nervous system disorders selected from the group of anxiety, schizophrenia, migraine, depression, and epilepsy. The invention is also directed to pharmaceutical compositions and processes to prepare such compounds and compositions, as well as to the use of such compounds for the prevention and treatment of such diseases in which mGluR2 is involved. |
| 主权项 |
1. A compound according to the general Formula (I),a pharmaceutically acceptable acid or base addition salt thereof, or a stereochemically isomeric form thereof, wherein
V1 is selected from the group consisting of an unsubstituted bivalent saturated, straight or branched hydrocarbon radical having from 1 to 6 carbon atoms; M1 is selected from the group consisting of hydrogen; cycloC3-7alkyl; phenyl optionally substituted with OCF3 or F; phenyloxy-; and tetrahydropyranyl; L is selected from the group consisting of a covalent bond; —O—; —OCH2—; NR7—; wherein R7, is selected from the group consisting of hydrogen and unsubstituted C1-3alkyl; R2 and R3 are hydrogen; A is piperidinyl selected from the group consisting ofwherein n is an integer equal to 0, 1, or 2;
R4 is, when present, at any of b, or c positions and is selected from the group consisting of C1-6-alkyl; C1-6-alkyloxy; C1-6-alkyloxycarbonyl-; polyhaloC1-3alkyl-; Het3; Het3-C1-6-alkyl-; Het3-oxy-; Het3-oxy-C1-6-alkyl-; Het3-C1-6-alkyloxy; —NRaRb; C1-6-alkyl-NRaRb; wherein Ra and Rb are selected from the group consisting of hydrogen, C1-6-alkyl, and C3-7-cycloalkyl; and Het3 is selected from the group consisting of pyridinyl; pyrimidinyl; pyridazinyl; pyrrolyl; indolyl; morpholinyl; oxadiazolyl; benzoxazolyl; benzofuranyl; indolinyl; 1,2,3,4-tetrahydro-isoquinolinyl; phthalazinyl; and benzo[1,3]dioxolyl wherein each radical is optionally substituted with 1 or 2 substituents, each independently selected from the group consisting of halo, C1-6alkyl, C3-7-cycloalkyl, polyhaloC1-3alkyl, cyano, mono(C1-6alkyl)amino, oxo, phenyl, morpholinyl, and C1-3alkyloxy. |
