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BioAssay: AID 143084

Affinity for the glycine binding site of NMDA receptor by inhibition of [3H]5,7-dichlorokynurenic acid ([3H]DCKA) binding to rat brain synaptic membrane

A series of tricyclic quinoxalinediones, 5,6-dihydro-1H-pyrrolo[1,2,3-de]quinoxaline-2,3-diones and 6,7-dihydro-1H,5H-pyrido[1,2,3-de]quinoxaline-2,3-diones, were synthesized and was evaluated for their affinity for the glycine binding site of the NMDA receptor using a [3H]-5,7-dichlorokynurenic acid binding assay. The six-membered ring-fused tricyclic quinoxalinedione 18g (Ki = 9.9 nM) displayed more ..
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 Tested Compounds
 Tested Compounds
All(24)
 
 
Active(21)
 
 
Unspecified(3)
 
 
 Tested Substances
 Tested Substances
All(24)
 
 
Active(21)
 
 
Unspecified(3)
 
 
 Related BioAssays
 Related BioAssays
AID: 143084
Data Source: ChEMBL (140323)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-05-21
Modify Date: 2014-05-19

Data Table ( Complete ):           View Active Data    View All Data
BioActive Compounds: 21
Description:
Title: Tricyclic quinoxalinediones: 5,6-dihydro-1H-pyrrolo[1,2,3-de] quinoxaline-2,3-diones and 6,7-dihydro-1H,5H-pyrido[1,2,3-de] quinoxaline-2,3-diones as potent antagonists for the glycine binding site of the NMDA receptor.

Abstract: A series of tricyclic quinoxalinediones, 5,6-dihydro-1H-pyrrolo[1,2,3-de]quinoxaline-2,3-diones and 6,7-dihydro-1H,5H-pyrido[1,2,3-de]quinoxaline-2,3-diones, were synthesized and was evaluated for their affinity for the glycine binding site of the NMDA receptor using a [3H]-5,7-dichlorokynurenic acid binding assay. The six-membered ring-fused tricyclic quinoxalinedione 18g (Ki = 9.9 nM) displayed high affinity for the glycine site. The anilide derivative 20g (Ki = 2.6 nM) was 4-fold more potent than 18g and as potent as L-689,560, one of the most potent glycine antagonists so far prepared. Although the carboxylic acid derivative of the corresponding five-membered ring-fused tricyclic quinoxalinedione 18e (Ki = 7.3 nM) had affinity comparable to that of 18g, the anilide derivative 20e largely decreased in the affinity in contrast to 20g. Enantiomers 23g, 24g, 25g, and 26g were prepared and tested. Only the S enantiomer 25g (Ki = 0.96 nM) retained the affinity among the anilide derivatives, whereas both enantiomers 23g (Ki = 2.3 nM) and 24g (Ki = 9.6 nM) were active among the carboxylic acid derivatives. The origin of the high affinity of carboxylic acid derivatives such as 18e and 18g would be a charge-charge interaction between the anionic carboxylate residues of the compounds and the cationic proton-donor site in the receptor.
(PMID: 7966156)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.
Putative Target:
ChEMBL Target ID: 104302
Target Type: PROTEIN COMPLEX GROUP
Pref Name: Glutamate NMDA receptor
Synonyms: GluN2D;Glutamate receptor ionotropic; NMDA 2D;Glutamate [NMDA] receptor subunit epsilon-4;N-methyl D-aspartate receptor subtype 2D;NMDAR2D;NR2D;GluN1;Glutamate receptor ionotropic; NMDA 1;Glutamate [NMDA] receptor subunit zeta-1;N-methyl-D-aspartate receptor subunit NR1;NMD-R1;GluN2A;Glutamate receptor ionotropic; NMDA 2A;Glutamate [NMDA] receptor subunit epsilon-1;N-methyl D-aspartate receptor subtype 2A;NMDAR2A;NR2A;GluN2B;Glutamate receptor ionotropic; NMDA 2B;Glutamate [NMDA] receptor subunit epsilon-2;N-methyl D-aspartate receptor subtype 2B;NMDAR2B;NR2B;GluN2C;Glutamate receptor ionotropic; NMDA 2C;Glutamate [NMDA] receptor subunit epsilon-3;N-methyl D-aspartate receptor subtype 2C;NMDAR2C;NR2C;GluN3A;Glutamate receptor chi-1;Glutamate receptor ionotropic; NMDA 3A;N-methyl-D-aspartate receptor;N-methyl-D-aspartate receptor subtype 3A;NMDAR-L;NMDAR-L1;NMDAR3A;NR3A;GluN3B;Glutamate receptor ionotropic; NMDA 3B;N-methyl-D-aspartate receptor subtype 3B;NMDAR3B;NR3B;
Gene Name: GluN2D;Grin2d;Grin1;Nmdar1;Grin2a;Grin2b;Grin2c;Grin3a;Grin3b;
Protein Accession: Q62645;P35439;Q00959;Q00960;Q00961;Q9R1M7;Q8VHN2;
Protein GI: 18202594;548379;3915771;548372;548374;51701631;51701630;
Organism: Rattus norvegicus
Tax ID: 10116
Target Classification: ion channel lgic glut nmda
Confidence: Multiple homologous protein targets may be assigned
Relationship Type: Homologous protein target assigned
Categorized Comment - additional comments and annotations
From ChEMBL:
Assay Type: Binding
Assay Data Source: Scientific Literature
Result Definitions
Show more
TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Ki*Ki PubChem standard valueFloatμM
3BEIBinding Efficiency Index(nM)Float
2SEISurface Efficiency Index(nM)Float
4LELigand EfficiencyFloat
5LLELipophilic Ligand EfficiencyFloat
6Ki activity commentKi activity commentString
7Ki standard flagKi standard flagInteger
8Ki qualifierKi qualifierString
9Ki published valueKi published valueFloatnM
10Ki standard valueKi standard valueFloatnM

* Activity Concentration.

Data Table (Concise)
Data Table ( Complete ):     View Active Data    View All Data
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