Structure-activity relationships for negative allosteric mGluR5 modulators

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

A series of compounds based on the mGluR5-selective ligand 2-methyl-6-(phenylethynyl)pyridine (MPEP) were designed and synthesized. The compounds were found to be either structural analogues of MPEP, substituted monomers, or dimeric analogues. All compounds retained mGluR5 selectivity with only weak or no activity at other mGluRs or iGluRs. The substituted analogue, 1,3-bis(pyridin-2-ylethynyl)benzene (19), is a potent negative modulator at mGluR5, whereas all other compounds lost potency relative to MPEP and showed that activity is highly dependent on the position of the nitrogen atom in the pyridine moieties. A homology modeling and ligand docking study was used to understand the binding mode and the observed selectivity of compound 19.
Udgave nummer3
Sider (fra-til)440-451
StatusUdgivet - 2012

Bibliografisk note

Keywords: allosteric modulators; cross-coupling; mGluR5; molecular modeling; structure–activity relationships

ID: 37587752