871362-31-1Relevant articles and documents
Metabotropic glutamate receptor 5 negative allosteric modulators: Discovery of 2-chloro-4-[1-(4-fluorophenyl)-2,5-dimethyl-1 H-imidazol-4-ylethynyl]pyridine (basimglurant, RO4917523), a promising novel medicine for psychiatric diseases
Jaeschke, Georg,Kolczewski, Sabine,Spooren, Will,Vieira, Eric,Bitter-Stoll, Nadia,Boissin, Patrick,Borroni, Edilio,Büttelmann, Bernd,Ceccarelli, Simona,Clemann, Nicole,David, Beatrice,Funk, Christoph,Guba, Wolfgang,Harrison, Anthony,Hartung, Thomas,Honer, Michael,Huwyler, J?rg,Kuratli, Martin,Niederhauser, Urs,P?hler, Axel,Peters, Jens-Uwe,Petersen, Ann,Prinssen, Eric,Ricci, Antonio,Rueher, Daniel,Rueher, Marianne,Schneider, Manfred,Spurr, Paul,Stoll, Theodor,T?nnler, Daniel,Wichmann, Jürgen,Porter, Richard H.,Wettstein, Joseph G.,Lindemann, Lothar
, p. 1358 - 1371 (2015/03/04)
Negative allosteric modulators (NAMs) of metabotropic glutamate receptor 5 (mGlu5) have potential for the treatment of psychiatric diseases including depression, fragile X syndrome (FXS), anxiety, obsessive-compulsive disorders, and levodopa induced dyskinesia in Parkinson's disease. Herein we report the optimization of a weakly active screening hit 1 to the potent and selective compounds chloro-4-[1-(4-fluorophenyl)-2,5-dimethyl-1H-imidazol-4-ylethynyl]pyridine (basimglurant, 2) and 2-chloro-4-((2,5-dimethyl-1-(4-(trifluoromethoxy)phenyl)-1H-imidazol-4-yl)ethynyl)pyridine (CTEP, 3). Compound 2 is active in a broad range of anxiety tests reaching the same efficacy but at a 10- to 100-fold lower dose compared to diazepam and is characterized by favorable DMPK properties in rat and monkey as well as an excellent preclinical safety profile and is currently in phase II clinical studies for the treatment of depression and fragile X syndrome. Analogue 3 is the first reported mGlu5 NAM with a long half-life in rodents and is therefore an ideal tool compound for chronic studies in mice and rats.
PHARMACEUTICAL COMPOSITIONS OF METABOTROPIC GLUTAMATE 5 RECEPTOR (MGLU5) ANTAGONISTS
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, (2012/03/08)
Pharmaceutical compositions of metabotropic glutamate 5 receptor (mGlu5) antagonists or a pharmacologically acceptable salt thereof are disclosed. The compositions contain the therapeutic active compound with non-ionic polymer and ionic polymer, binder and fillers in either matrix pellet, matrix tablet or coated pellets. The compositions provide a pH-independent in vitro release profile with NMT 70% in one hour, NMT 85% in 4 hour, and NLT 80% in 8 hours. The compositions are useful for the treatment of CNS disorders, such as Treatment-Resistant Depression (TRD) and Fragile X Syndrome.
PYRIDIN-4-YL-ETHYNYL-IMIDAZOLES AND PYRAZOLES AS MGLU5 RECEPTOR ANTAGONISTS
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Page/Page column 26, (2008/06/13)
The present invention relates to diazole derivatives of the general formula (I) wherein A, E, R1, Wand R3 are as defined in the claims and description, their use for the preparation of medicaments for treating diseases and processes