1. Discovery of a potent and brain penetrant mGluR5 positive allosteric modulator
- Author
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Andreas Ritzen, Christoffer Bundgaard, Robbin Brodbeck, Rikke Sindet, Nannette Svendsen, and Morten Hentzer
- Subjects
Allosteric modulator ,Receptor, Metabotropic Glutamate 5 ,Clinical Biochemistry ,Allosteric regulation ,Administration, Oral ,Pharmaceutical Science ,Pharmacology ,Receptors, Metabotropic Glutamate ,Biochemistry ,Mice ,Structure-Activity Relationship ,chemistry.chemical_compound ,Allosteric Regulation ,Heterocyclic Compounds ,In vivo ,mental disorders ,Drug Discovery ,Animals ,Potency ,Molecular Biology ,Metabotropic glutamate receptor 5 ,Organic Chemistry ,Brain ,Biological activity ,Rats ,chemistry ,Alkynes ,Molecular Medicine ,Penetrant (biochemical) ,Lead compound - Abstract
This Letter describes the discovery of a novel series of mGluR5 positive allosteric modulators (PAMs). The lead compound, 11c, exhibits excellent potency (EC(50)=30 nM) in vitro, and reaches high brain levels in both rats and mice after oral administration.
- Published
- 2009
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