Quinoline carboxamide and quinoline carbonitrile derivatives as mglur2-negative allosteric modulators, compositions, and their use

• Main Authors: BUNGARD CHRISTOPHER JAMES, MENG ZHAOYANG, MANLEY PETER J, DE LEON PABLO, MANIKOWSKI JESSE JOSEF, MEISSNER ROBERT, PERKINS JAMES J, SHU YOUHENG, RUDD MICHAEL T, CONVERSO ANTONELLA, HARTINGH TIMOTHY JOHN, HANNEY BARBARA
• Format: Patent
• Language: English
• Published: 28.10.2016
• Subjects: AGRICULTURE; ANIMAL HUSBANDRY; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES, AS HERBICIDES; CHEMISTRY; FISHING; FORESTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HUNTING; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES; PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTSTHEREOF; TRAPPING

Disclosed are quinoline carboxamide and quinoline carbonitrile compounds of formula (I) wherein ring A, RQ, -L-, R1, n, R2, and R3 are as defined in the specification. The compounds are useful as non-competitive metabotropic glutamate receptor 2 (mGluR2) antagonists, or mGluR2 negative allosteric modulators (NAMs), and in methods of treating diseases or disorders in which the mGluR2-NAM receptor is involved, such as Alzheimer's disease, cognitive impairment, schizophrenia and other mood disorders, pain disorders and sleep disorders. Examples of a compound of formula (I) are: 4-(4-fluorophenyl)-7-((3-methyl-2,5-dioxoimidazolidin-1-yl)methyl)quinoline-2-carboxamide 7-[(2,5-dioxopyrrolidin-1-yl)methyl]-4-(4-methoxyphenyl)quinoline-2-carboxamide Ethyl-1-{ [2-carbamoyl-4-(4-fluorophenyl)quinolin-7-yl]methyl} -3-(trifluoromethyl)-1H-pyrazole-4-carboxylate 7-[(4,4-dimethyl-2,6-dioxopiperidin-1-yl)methyl]-4-(4-fluorophenyl)quinoline-2-carbonitrile