1056465-06-5Relevant academic research and scientific papers
N-(1-HYDROXY-3-(PYRROLIDINYL)PROPAN-2-YL)PYRROLIDINE-3-CARBOXAMIDE DERIVATIVES AS GLUCOSYLCERAMIDE SYNTHASE INHIBITORS
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Paragraph 000254; 000320; 000321, (2015/05/19)
Described herein are compounds of Formula I, methods of making such compounds, pharmaceutical compositions and medicaments containing such compounds, and compounds I for use to treat or prevent diseases or conditions associated with the enzyme glucosylceramide synthase (GCS).
Discovery of 1,4-disubstituted 3-cyano-2-pyridones: A new class of positive allosteric modulators of the metabotropic glutamate 2 receptor
Cid, Jose María,Duvey, Guillaume,Tresadern, Gary,Nhem, Vanthea,Furnari, Rocco,Cluzeau, Philippe,Vega, Juan Antonio,De Lucas, Ana Isabel,Matesanz, Encarnación,Alonso, José Manuel,Linares, María Lourdes,Andrés, José Ignacio,Poli, Sonia M.,Lutjens, Robert,Himogai, Hassan,Rocher, Jean-Philippe,MacDonald, Gregor J.,Oehlrich, Daniel,Lavreysen, Hilde,Ahnaou, Abdelah,Drinkenburg, Wilhelmus,MacKie, Claire,Trabanco, Andrés A.
experimental part, p. 2388 - 2405 (2012/05/05)
The discovery and characterization of compound 48, a selective and in vivo active mGlu2 receptor positive allosteric modulator (PAM), are described. A key to the discovery was the rational exploration of the initial HTS hit 13 guided by an overlay model built with reported mGlu2 receptor PAM chemotypes. The initial weak in vitro activity of the hit 13 was quickly improved, although compounds still had suboptimal druglike properties. Subsequent modulation of the physicochemical properties resulted in compounds having a more balanced profile, combining good potency and in vivo pharmacokinetic properties. Final refinement by addressing cardiovascular safety liabilities led to the discovery of compound 48. Besides good potency, selectivity, and ADME properties, compound 48 displayed robust in vivo activity in a sleep-wake electroencephalogram (sw-EEG) assay consistent with mGlu2 receptor activation, in accordance with previous work from our laboratories.
Imidazo[1,2-a]pyridines: Orally active positive allosteric modulators of the metabotropic glutamate 2 receptor
Trabanco, Andrés A.,Tresadern, Gary,MacDonald, Gregor J.,Vega, Juan Antonio,De Lucas, Ana Isabel,Matesanz, Encarnación,García, Aránzazu,Linares, María Lourdes,Alonso De Diego, Sergio A.,Alonso, José Manuel,Oehlrich, Daniel,Ahnaou, Abdelah,Drinkenburg, Wilhelmus,MacKie, Claire,Andrés, José Ignacio,Lavreysen, Hilde,Cid, José María
experimental part, p. 2688 - 2701 (2012/06/01)
Advanced leads of an imidazopyridine series of positive allosteric modulators of the metabotropic glutamate 2 (mGlu2) receptor are reported. The optimization of in vitro ADMET and in vivo pharmacokinetic properties led to the identification of 27o. With g
7-ARYL-1,2,4-TRIAZOLO[4,3-A]PYRIDINE DERIVATIVES AND THEIR USE AS POSITIVE ALLOSTERIC MODULATORS OF MGLUR2 RECEPTORS
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Page/Page column 60, (2010/12/17)
The present invention relates to novel triazolo[4,3-a]pyridine derivatives of Formula (I) wherein all radicals are as defined in the claims. The compounds according to the invention are positive allosteric modulators of the metabotropic glutamate receptor 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. The invention is also directed to pharmaceutical compositions comprising such compounds, to processes to prepare such compounds and compositions, and to the use of such compounds for the prevention or treatment of neurological and psychiatric disorders and diseases in which mGluR2 is involved.
