FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2890742620> ?p ?o ?g. }

• W2890742620 endingPage "269" @default.
• W2890742620 startingPage "259" @default.
• W2890742620 abstract "GluN2A containing N-methyl-D-aspartate receptors (NMDARs) are important ion channels in the central nervous system and highly involved in several different neurophysiological but also neuropathophysiological processes. However, current understanding of the contribution of GluN2A containing NMDARs in these processes is incomplete. Therefore, highly selective compounds are required to further investigate these ion channels. In 2010, TCN-201 (2), one of the first selective negative allosteric modulators was reported. While the binding site of 2 and the influence of the substitution pattern of the benzenesulfonamide part has been reported recently, detailed structure-activity-relationships of the diacylhydrazine part and the linked phenyl moiety are still missing. In order to examine the critical interactions between these moieties and the binding site, several TCN-201 analogs with modified diacylhydrazine part were synthesized. The negative allosteric effect was recorded by two-electrode voltage clamp (TEVC) experiments using GluN1a/GluN2A expressing Xenopus laevis oocytes. Our data led to the conclusion, that the terminal phenyl moiety is involved in a cation-π-interaction with the guanidinium moiety of Arg755 of the GluN1a subunit, which plays a crucial role for high activity. Additionally, structure optimization by replacing the phenyl moiety with a thiophen-2-yl (10c), indol-2-yl (10g) or indol-3-yl (10h) moiety significantly increased the activity of 2 by the factor 2.5. At a test compound concentration of 200 nM, the negative allosteric effect of the most potent ligands 10c, 10h and 17 was significantly influenced by the glycine concentration. Although glycine dependency is higher than those of the lead compound 4, 10c and 17 showed significantly higher negative allosteric effects than 4 at glycine concentrations from 1 μM up to 10 μM. The potent GluN2A-NMDA receptor inhibitors 10c, 10h and 17 did not influence the ion current of GluN2B-NMDA receptors." @default.
• W2890742620 created "2018-09-27" @default.
• W2890742620 creator A5015679062 @default.
• W2890742620 creator A5040260186 @default.
• W2890742620 creator A5041499989 @default.
• W2890742620 creator A5045112682 @default.
• W2890742620 creator A5049648947 @default.
• W2890742620 creator A5053327437 @default.
• W2890742620 creator A5071739030 @default.
• W2890742620 date "2018-10-01" @default.
• W2890742620 modified "2023-09-27" @default.
• W2890742620 title "Systematic variation of the benzoylhydrazine moiety of the GluN2A selective NMDA receptor antagonist TCN-201" @default.
• W2890742620 cites W1600539804 @default.
• W2890742620 cites W1966517040 @default.
• W2890742620 cites W1970393142 @default.
• W2890742620 cites W1978329946 @default.
• W2890742620 cites W1978507389 @default.
• W2890742620 cites W1998347917 @default.
• W2890742620 cites W1999848385 @default.
• W2890742620 cites W2000378579 @default.
• W2890742620 cites W2007208313 @default.
• W2890742620 cites W2007726238 @default.
• W2890742620 cites W2014765513 @default.
• W2890742620 cites W2016542252 @default.
• W2890742620 cites W2017329375 @default.
• W2890742620 cites W2025420397 @default.
• W2890742620 cites W2025801062 @default.
• W2890742620 cites W2031901496 @default.
• W2890742620 cites W2044958998 @default.
• W2890742620 cites W2065169750 @default.
• W2890742620 cites W2081678712 @default.
• W2890742620 cites W2083966839 @default.
• W2890742620 cites W2084240270 @default.
• W2890742620 cites W2084494940 @default.
• W2890742620 cites W2085313140 @default.
• W2890742620 cites W2090166619 @default.
• W2890742620 cites W2100824868 @default.
• W2890742620 cites W2108909652 @default.
• W2890742620 cites W2154792548 @default.
• W2890742620 cites W2162454135 @default.
• W2890742620 cites W2260891265 @default.
• W2890742620 cites W2264863007 @default.
• W2890742620 cites W2519747458 @default.
• W2890742620 cites W2579245005 @default.
• W2890742620 cites W2588124145 @default.
• W2890742620 doi "https://doi.org/10.1016/j.ejmech.2018.09.006" @default.
• W2890742620 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/30218911" @default.
• W2890742620 hasPublicationYear "2018" @default.
• W2890742620 type Work @default.
• W2890742620 sameAs 2890742620 @default.
• W2890742620 citedByCount "7" @default.
• W2890742620 countsByYear W28907426202020 @default.
• W2890742620 countsByYear W28907426202021 @default.
• W2890742620 countsByYear W28907426202022 @default.
• W2890742620 countsByYear W28907426202023 @default.
• W2890742620 crossrefType "journal-article" @default.
• W2890742620 hasAuthorship W2890742620A5015679062 @default.
• W2890742620 hasAuthorship W2890742620A5040260186 @default.
• W2890742620 hasAuthorship W2890742620A5041499989 @default.
• W2890742620 hasAuthorship W2890742620A5045112682 @default.
• W2890742620 hasAuthorship W2890742620A5049648947 @default.
• W2890742620 hasAuthorship W2890742620A5053327437 @default.
• W2890742620 hasAuthorship W2890742620A5071739030 @default.
• W2890742620 hasConcept C104292427 @default.
• W2890742620 hasConcept C104317684 @default.
• W2890742620 hasConcept C12554922 @default.
• W2890742620 hasConcept C166342909 @default.
• W2890742620 hasConcept C170493617 @default.
• W2890742620 hasConcept C185592680 @default.
• W2890742620 hasConcept C2776038425 @default.
• W2890742620 hasConcept C2776568683 @default.
• W2890742620 hasConcept C2777756961 @default.
• W2890742620 hasConcept C2779535977 @default.
• W2890742620 hasConcept C515207424 @default.
• W2890742620 hasConcept C55493867 @default.
• W2890742620 hasConcept C67018056 @default.
• W2890742620 hasConcept C71240020 @default.
• W2890742620 hasConcept C86803240 @default.
• W2890742620 hasConceptScore W2890742620C104292427 @default.
• W2890742620 hasConceptScore W2890742620C104317684 @default.
• W2890742620 hasConceptScore W2890742620C12554922 @default.
• W2890742620 hasConceptScore W2890742620C166342909 @default.
• W2890742620 hasConceptScore W2890742620C170493617 @default.
• W2890742620 hasConceptScore W2890742620C185592680 @default.
• W2890742620 hasConceptScore W2890742620C2776038425 @default.
• W2890742620 hasConceptScore W2890742620C2776568683 @default.
• W2890742620 hasConceptScore W2890742620C2777756961 @default.
• W2890742620 hasConceptScore W2890742620C2779535977 @default.
• W2890742620 hasConceptScore W2890742620C515207424 @default.
• W2890742620 hasConceptScore W2890742620C55493867 @default.
• W2890742620 hasConceptScore W2890742620C67018056 @default.
• W2890742620 hasConceptScore W2890742620C71240020 @default.
• W2890742620 hasConceptScore W2890742620C86803240 @default.
• W2890742620 hasFunder F4320320879 @default.
• W2890742620 hasLocation W28907426201 @default.
• W2890742620 hasLocation W28907426202 @default.
• W2890742620 hasOpenAccess W2890742620 @default.
• W2890742620 hasPrimaryLocation W28907426201 @default.

• next