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cc by-nc-nd (c) Elsevier Masson SAS, 2017
Si us plau utilitzeu sempre aquest identificador per citar o enllaçar aquest document: https://hdl.handle.net/2445/147557

Positional isomers of bispyridine benzene derivatives induce efficacy changes on mGlu5 negative allosteric modulation

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Modulation of metabotropic glutamate receptor 5 (mGlu5) with partial allosteric antagonists has received increased interest due to their favourable in vivo activity profiles compared to the unfavourable side-effects of full inverse agonists. Here we report on a series of bispyridine benzene derivatives with a functional molecular switch affecting antagonistic efficacy, shifting from inverse agonism to partial antagonism with only a single change in the substitution pattern of the benzene ring. These efficacy changes are explained through computational docking, revealing two different receptor conformations of different energetic stability and different positional isomer binding preferences.

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GÓMEZ SANTACANA, Xavier, DALTON, James a. r., ROVIRA, Xavier, PIN, Jean-philippe, GOUDET, Cyril, GOROSTIZA LANGA, Pablo ignacio, GIRALDO, Jesús, LLEBARIA SOLDEVILA, Amadeu. Positional isomers of bispyridine benzene derivatives induce efficacy changes on mGlu5 negative allosteric modulation. _European Journal of Medicinal Chemistry_. 2017. Vol. 127, núm. 567-576. [consulta: 25 de gener de 2026]. ISSN: 0223-5234. [Disponible a: https://hdl.handle.net/2445/147557]

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