Imidazo[1,2-a]pyridines: Orally Active Positive Allosteric Modulators of the Metabotropic Glutamate 2 Receptor

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 good potency and selectivity for the mGlu2 rec...

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Veröffentlicht in:Journal of medicinal chemistry 2012-03, Vol.55 (6), p.2688-2701
Hauptverfasser: 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
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Sprache:eng
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Zusammenfassung: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 good potency and selectivity for the mGlu2 receptor, 27o affected sleep–wake architecture in rats after oral treatment, which we have previously shown to be indicative of mGlu2 receptor-mediated central activity.
ISSN:0022-2623
1520-4804
DOI:10.1021/jm201561r