ArticleNeurochemistry international2012
Coumarin-3-carboxylic acid derivatives as potentiators and inhibitors of recombinant and native N-methyl-D-aspartate receptors.
Article in Neurochemistry international, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 44 citations in OpenAlex.
- Glutamate Receptors and Synaptic Plasticity in Health and Disease: A Personal Journey.Hippocampus · 2026Review
- Cage effects on synaptic plasticity and its modulation in a mouse model of fragile X syndrome.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Article
- Incremental induction of NMDAR-STP and NMDAR-LTP in the CA1 area of ventral hippocampal slices relies on graded activation of discrete NMDA receptors.Philosophical transactions of the Royal Society of London. Series B, Biological sciences · 2024Article
- Differential regulation of STP, LTP and LTD by structurally diverse NMDA receptor subunit-specific positive allosteric modulators.Neuropharmacology · 2022Article
- Distinct GluN1 and GluN2 Structural Determinants for Subunit-Selective Positive Allosteric Modulation ofACS chemical neuroscience · 2021Article
- Positive and Negative Allosteric Modulators of N-Methyl-d-aspartate (NMDA) Receptors: Structure-Activity Relationships and Mechanisms of Action.Journal of medicinal chemistry · 2019Review
- Mechanism and properties of positive allosteric modulation of N-methyl-d-aspartate receptors by 6-alkyl 2-naphthoic acid derivatives.Neuropharmacology · 2017Article
- A single-channel mechanism for pharmacological potentiation of GluN1/GluN2A NMDA receptors.Scientific reports · 2017Article
- The Structure-Activity Relationship of a Tetrahydroisoquinoline Class of N-Methyl-d-Aspartate Receptor Modulators that Potentiates GluN2B-Containing N-Methyl-d-Aspartate Receptors.Journal of medicinal chemistry · 2017Article
- Enhancing NMDA Receptor Function: Recent Progress on Allosteric Modulators.Neural plasticity · 2017Review
- Synthesis, Fluorescence Properties, and Antiproliferative Potential of Several 3-Oxo-3H-benzo[f]chromene-2-carboxylic Acid Derivatives.Molecules (Basel, Switzerland) · 2015Article
- NMDA receptor modulators: an updated patent review (2013-2014).Expert opinion on therapeutic patents · 2014Review
- Synthesis and structure activity relationship of tetrahydroisoquinoline-based potentiators of GluN2C and GluN2D containing N-methyl-D-aspartate receptors.Journal of medicinal chemistry · 2013Article
- The NMDA receptor as a target for cognitive enhancement.Neuropharmacology · 2013Review
- Novel NMDA receptor modulators: an update.Expert opinion on therapeutic patents · 2012Review
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 2 countries.
Funding
Abstract
N-Methyl-d-aspartate receptors (NMDARs) are known to be involved in a range of neurological and neurodegenerative disorders and consequently the development of compounds that modulate the function of these receptors has been the subject of intense interest. We have recently reported that 6-bromocoumarin-3-carboxylic acid (UBP608) is a negative allosteric modulator with weak selectivity for GluN2A-containing NMDARs. In the present study, a series of commercially available and newly synthesized coumarin derivatives have been evaluated in a structure-activity relationship (SAR) study as modulators of recombinant NMDAR activity. The main conclusions from this SAR study were that substituents as large as iodo were accommodated at the 6-position and that 6,8-dibromo or 6,8-diiodo substitution of the coumarin ring enhanced the inhibitory activity at NMDARs. These coumarin derivatives are therefore excellent starting points for the development of more potent and GluN2 subunit selective inhibitors, which may have application in the treatment of a range of neurological disorders such as neuropathic pain, epilepsy and depression. Surprisingly, 4-methyl substitution of UBP608 to give UBP714, led to conversion of the inhibitory activity of UBP608 into potentiating activity at recombinant GluN1/GluN2 receptors. UBP714 also enhanced NMDAR mediated field EPSPs in the CA1 region of the hippocampus. UBP714 is therefore a novel template for the development of potent and subunit selective NMDAR potentiators that may have therapeutic applicability in the treatment of patients with cognitive deficits or schizophrenia.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.