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http://hdl.handle.net/2445/147557
Title: | Positional isomers of bispyridine benzene derivatives induce efficacy changes on mGlu5 negative allosteric modulation |
Author: | Gómez Santacana, Xavier Dalton, James A. R. Rovira, Xavier Pin, Jean-Philippe Goudet, Cyril Gorostiza Langa, Pablo Ignacio Giraldo, Jesús Llebaria Soldevila, Amadeu |
Keywords: | Receptors de neurotransmissors Molècules Neurotransmitter receptors Molecules |
Issue Date: | 15-Feb-2017 |
Abstract: | 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. |
Note: | Versió postprint del document publicat a: http://dx.doi.org/10.1016/j.ejmech.2017.01.013 |
It is part of: | European Journal of Medicinal Chemistry, 2017, vol. 127, p. 567-576 |
URI: | http://hdl.handle.net/2445/147557 |
Related resource: | http://dx.doi.org/10.1016/j.ejmech.2017.01.013 |
ISSN: | 0223-5234 |
Appears in Collections: | Articles publicats en revistes (Institut de Bioenginyeria de Catalunya (IBEC)) Publicacions de projectes de recerca finançats per la UE |
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L01_2017_European Journal of Medicinal Chemistry_127_567_OA.pdf | 1.22 MB | Adobe PDF | View/Open |
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