Negative allosteric modulators of NMDA receptors with GluN2B subunit: Alanine‐derived benzoxazolone bioisosteres of 2‐methyl‐3‐benzazepine‐1,7‐diols
Sign Up to like & getrecommendations! Published in 2022 at "Archiv der Pharmazie"
DOI: 10.1002/ardp.202200177
Abstract: Inspired by besonprodil, the phenol of potent negative allosteric modulators of GluN2B‐N‐methyl‐d‐aspartate (NMDA) receptors was replaced by a benzoxazolone system. To increase the similarity to the lead compounds, an additional methyl moiety was installed in… read more here.
Keywords: nmda receptors; allosteric modulators; moiety; benzoxazolone ... See more keywords
The structural determinants of the bitopic binding mode of a negative allosteric modulator of the dopamine D2 receptor
Sign Up to like & getrecommendations! Published in 2018 at "Biochemical Pharmacology"
DOI: 10.1016/j.bcp.2018.01.002
Abstract: Graphical abstract Figure. No caption available. ABSTRACT SB269652 is a negative allosteric modulator of the dopamine D2 receptor (D2R) yet possesses structural similarity to ligands with a competitive mode of interaction. In this study, we… read more here.
Keywords: allosteric modulator; negative allosteric; dopamine receptor; pharmacology ... See more keywords
Negative allosteric modulation of GABAARs at α5 subunit-containing benzodiazepine sites reverses stress-induced anhedonia and weakened synaptic function in mice
Sign Up to like & getrecommendations! Published in 2021 at "Biological psychiatry"
DOI: 10.1016/j.biopsych.2021.11.024
Abstract: BACKGROUND Abnormal reward processing, typically anhedonia, is a hallmark of human depression and is accompanied by altered functional connectivity in reward circuits. Negative allosteric modulators of GABAA (gamma-aminobutyric acid A) receptors (GABA-NAMs) have rapid antidepressant-like… read more here.
Keywords: benzodiazepine site; stress; mice; gaba nams ... See more keywords
Systematic variation of the benzoylhydrazine moiety of the GluN2A selective NMDA receptor antagonist TCN-201.
Sign Up to like & getrecommendations! Published in 2018 at "European journal of medicinal chemistry"
DOI: 10.1016/j.ejmech.2018.09.006
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… read more here.
Keywords: tcn 201; nmda receptor; negative allosteric; moiety ... See more keywords
Subtle modifications to a thieno[2,3-d]pyrimidine scaffold yield negative allosteric modulators and agonists of the dopamine D2 receptor.
Sign Up to like & getrecommendations! Published in 2019 at "European journal of medicinal chemistry"
DOI: 10.1016/j.ejmech.2019.01.061
Abstract: We recently described a structurally novel series of negative allosteric modulators (NAMs) of the dopamine D2 receptor (D2R) based on thieno[2,3-d]pyrimidine 1, showing it can be structurally simplified to reveal low molecular weight, fragment-like NAMs… read more here.
Keywords: allosteric modulators; thieno pyrimidine; negative allosteric; dopamine receptor ... See more keywords
Distinctive binding properties of the negative allosteric modulator, [3H]SB269,652, at recombinant dopamine D3 receptors
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DOI: 10.1016/j.ejphar.2017.12.002
Abstract: ABSTRACT Recently, employing radioligand displacement and functional coupling studies, we demonstrated that SB269,652 (N‐[(1r,4r)−4‐[2‐(7‐cyano‐1,2,3,4‐tetrahydroisoquinolin‐2‐yl)ethyl]cyclohexyl]−1H‐indole‐2‐carboxamide) interacts in an atypical manner with dopamine D3 receptor displaying a unique profile reminiscent of a negative allosteric ligand. Here, we… read more here.
Keywords: allosteric modulator; negative allosteric; dopamine; sb269 652 ... See more keywords
Antidepressant Effects and Mechanisms of Group II mGlu Receptor-Specific Negative Allosteric Modulators
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DOI: 10.1016/j.neuron.2019.12.011
Abstract: In this issue of Neuron, Joffe et al. (2020) assess the antidepressant-relevant effects and underlying neural mechanisms of negative allosteric modulators selective for either metabotropic glutamate receptors 2 (mGlu2) or 3 (mGlu3). Negative modulation of both… read more here.
Keywords: mechanisms group; effects mechanisms; negative allosteric; allosteric modulators ... See more keywords
Identification by virtual screening and functional characterisation of novel positive and negative allosteric modulators of the α7 nicotinic acetylcholine receptor
Sign Up to like & getrecommendations! Published in 2018 at "Neuropharmacology"
DOI: 10.1016/j.neuropharm.2018.07.009
Abstract: ABSTRACT Several previous studies have demonstrated that the activity of neurotransmitters acting on ligand‐gated ion channels such as the nicotinic acetylcholine receptor (nAChR) can be altered by compounds binding to allosteric modulatory sites. In the… read more here.
Keywords: positive negative; negative allosteric; nicotinic acetylcholine; allosteric modulators ... See more keywords
Multiparameter Optimization of Naphthyridine Derivatives as Selective α5-GABAA Receptor Negative Allosteric Modulators.
Sign Up to like & getrecommendations! Published in 2022 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.2c00414
Abstract: The discovery and characterization of novel naphthyridine derivatives with selective α5-GABAAR negative allosteric modulator (NAM) activity are disclosed. Utilizing a scaffold-hopping strategy, fused [6 + 6] bicyclic scaffolds were designed and synthesized. Among these, 1,6-naphthyridinones… read more here.
Keywords: selective gabaa; optimization naphthyridine; derivatives selective; multiparameter optimization ... See more keywords
Discovery of 6,7-Dihydropyrazolo[1,5-a]pyrazin-4(5H)-one Derivatives as mGluR2 Negative Allosteric Modulators with In Vivo Activity in a Rodent's Model of Cognition.
Sign Up to like & getrecommendations! Published in 2024 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.4c01227
Abstract: Allosteric modulators of the metabotropic group II receptors, mGluR2 and mGluR3, have been widely explored due to their ability to modulate cognitive and neurological functions in mood disorders, although none have been approved yet. In… read more here.
Keywords: allosteric modulators; negative allosteric; dihydropyrazolo pyrazin; mglur2 negative ... See more keywords
Enantiomerically Pure Indazole Bioisosteres of Ifenprodil and Ro 25-6981 as Negative Allosteric Modulators of NMDA Receptors with the GluN2B Subunit.
Sign Up to like & getrecommendations! Published in 2024 at "Journal of medicinal chemistry"
DOI: 10.1021/acs.jmedchem.4c02035
Abstract: Administration of negative allosteric modulators of GluN2B subunit-containing NMDA receptors such as Ro 25-6981 (1) and ifenprodil (2) results in neuroprotective effects. In this study, the phenol of 1 and 2 was replaced bioisosterically by… read more here.
Keywords: nmda receptors; allosteric modulators; indazole bioisosteres; negative allosteric ... See more keywords