| 摘要 |
The present invention relates to novel compounds, in particular novel pyridinone derivatives according to Formula (I);;wherein all radicals are as 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 having the formula (I)or a stereochemically isomeric form thereof, wherein
R1 is C1-6alkyl; or C1-3alkyl substituted with C3-7cycloalkyl, phenyl, or phenyl substituted with halo, trifluoromethyl or trifluoromethoxy; R2 is halo, trifluoromethyl, C1-3alkyl or cyclopropyl; R3 is hydrogen, fluoro, hydroxyl, hydroxyC1-3alkyl, hydroxyC1-3alkyloxy, fluoroC1-3alkyl, fluoroC1-3alkyloxy or cyano; and Ar is phenyl substituted with n radicals R4, wherein n is 1, 2 or 3; R4 is selected from the group consisting of hydrogen, halo, C1-3alkyl, hydroxyC1-3alkyl, polyhaloC1-3alkyl, cyano, hydroxyl, amino, carboxyl, C1-3alkyloxyC1-3alkyl, C1-3alkyloxy, polyhaloC1-3alkyloxy, C1-3alkylcarbonyl, mono- and di(C1-3alkyl)amino, and morpholinyl; or two vicinal R4 radicals taken together form a bivalent radical of formula
—N═CH—NH— (a),—CH═CH—NH— (b), or—O—CH2—CH2—NH— (c); orR3 and a R4 radical in ortho position taken together form a bivalent radical of formula
—CH2—O— (d), or—O—CH2— (e); or a pharmaceutically acceptable salt or a solvate thereof. |
