Discovery of a potent and brain penetrant mGluR5 positive allosteric modulator

Andreas Ritzén; Rikke Sindet; Morten Hentzer; Nannette Svendsen; Robbin M Brodbeck; Christoffer Bundgaard

doi:10.1016/j.bmcl.2009.04.095

Discovery of a potent and brain penetrant mGluR5 positive allosteric modulator

Bioorg Med Chem Lett. 2009 Jun 15;19(12):3275-8. doi: 10.1016/j.bmcl.2009.04.095. Epub 2009 Apr 24.

Authors

Andreas Ritzén¹, Rikke Sindet, Morten Hentzer, Nannette Svendsen, Robbin M Brodbeck, Christoffer Bundgaard

Affiliation

¹ Medicinal Chemistry Research DK, H. Lundbeck A/S, Ottiliavej 9, DK-2500 Valby, Denmark. [email protected]

PMID: 19443216
DOI: 10.1016/j.bmcl.2009.04.095

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.

MeSH terms

Administration, Oral
Alkynes / chemistry*
Alkynes / pharmacology
Allosteric Regulation
Animals
Brain / metabolism*
Drug Discovery
Heterocyclic Compounds / chemistry*
Heterocyclic Compounds / pharmacology
Mice
Rats
Receptor, Metabotropic Glutamate 5
Receptors, Metabotropic Glutamate / agonists*
Structure-Activity Relationship

Substances

Alkynes
Grm5 protein, mouse
Grm5 protein, rat
Heterocyclic Compounds
Receptor, Metabotropic Glutamate 5
Receptors, Metabotropic Glutamate