| 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 method for treating, preventing, ameliorating, or reducing the risk of a condition that is affected or facilitated by neuromodulatory effect of an mGluR2 positive allosteric modulator in a mammal, the method comprising administering to the mammal in need thereof an mGluR2 positive allosteric modulator of general formula (I): or a pharmaceutically acceptable salt or stereochemically isomeric form thereof, wherein V1 is an unsubstituted bivalent saturated straight or branched hydrocarbon radical having from 1 to 6 carbon atoms; M1 is hydrogen; cycloC3-7alkyl; phenyl optionally substituted with OCF3 or F, phenyloxy; or tetrahydropyranyl; L is a covalent bond; —O—; —OCH2—; or —NR7—; wherein R7 is hydrogen or an unsubstituted C1-3alkyl; R2 and R3 are hydrogen; A is piperidinyl, of a form: wherein n is 0, 1 or 2; R4 is, when present at any of b or c positions, C1-6alkyl, C1-6alkyloxy, C1-6alkyloxycarbonyl; polyhaloC1-3alkyl; Het3; Het3-C1-6alkyl; Het3-oxy; Het3-oxy-C1-6alkyl; Het3-C1-6alkyloxy; —NRaRb; or C1-6alkyl-NRaRb; wherein Ra and Rb are hydrogen, C1-6alkyl or C3-7cycloalkyl; Het3 is pyridinyl; pyrimidinyl; pyridazinyl; pyrrolyl; indolyl; morpholinyl; oxadiazolyl; benzoxazolyl; benzofuranyl; indolinyl; 1,2,3,4-tetrahydro-isoquinolinyl; phthalazinyl; or benzo[1,3]dioxolyl; wherein each radical is optionally substituted with 1 or 2 substituents, each independently halo, C1-6alkyl, C3-7cycloalkyl, polyhaloC1-3alkyl, cyano, mono(C1-6alkyl)amino, oxo, phenyl, morpholinyl, or C1-3alkyloxy. |
