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BioAssay: AID 148680

Inhibition of [3H]U-69593 radioligand binding to Guinea pig opioid receptor kappa 1.

Derivatives of racemic and optically active 5-(3-hydroxyphenyl)-2-methylmorphan (5-(3-hydroxyphenyl)-2-methyl-2-azabicyclo[3.3.1]nonane, 1) were synthesized containing additional aromatic moieties, as an application of the message-address concept targeted at producing delta-opioid receptor selective ligands. In vitro radioreceptor binding studies in rat brain revealed that both of the parent more ..
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 Tested Compounds
 Tested Compounds
All(23)
 
 
Active(12)
 
 
Unspecified(11)
 
 
 Tested Substances
 Tested Substances
All(23)
 
 
Active(12)
 
 
Unspecified(11)
 
 
AID: 148680
Data Source: ChEMBL (145926)
BioAssay Type: Confirmatory, Concentration-Response Relationship Observed
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-05-21
Modify Date: 2014-08-24

Data Table ( Complete ):           View Active Data    View All Data
Target
Sequence: RecName: Full=Kappa-type opioid receptor; Short=K-OR-1; Short=KOR-1
Description ..   
Protein Family: Serpentine type 7TM GPCR chemoreceptor Srsx
Comment ..   

Gene:OPRK1     Related Protein 3D Structures     More BioActivity Data..
BioActive Compounds: 12
Description:
Title: Probes for narcotic receptor-mediated phenomena. 20. Alteration of opioid receptor subtype selectivity of the 5-(3-hydroxyphenyl)morphans by application of the message-address concept: preparation of delta-opioid receptor ligands.

Abstract: Derivatives of racemic and optically active 5-(3-hydroxyphenyl)-2-methylmorphan (5-(3-hydroxyphenyl)-2-methyl-2-azabicyclo[3.3.1]nonane, 1) were synthesized containing additional aromatic moieties, as an application of the message-address concept targeted at producing delta-opioid receptor selective ligands. In vitro radioreceptor binding studies in rat brain revealed that both of the parent enantiomers, (-)- and (+)-1, had a high affinity for the mu-opioid receptor (21 nM), a slight affinity for kappa 1-opioid receptors (approximately 800-900 nM), and less than 1000 nM affinity for the delta-opioid receptor (mu/delta IC50 ratio of < 0.02 for both). A derivative of (-)-1 containing an indole moiety fused at the C6-C7 position of the phenylmorphan nucleus, (-)-11, displayed a > 180-fold increase in affinity for the delta-opioid receptor with an IC50 value of 6 nM. The parent compound (-)-1 had only 26% agonist activity at 30 microM in the mouse vas deferens (delta) bioassay, whereas compound (-)-11 had an IC50 of 393 nM in this preparation, indicating the importance of the indole moiety in imparting delta-opioid agonist activity to the phenylmorphan (-)-11. A structure-activity relationship (SAR) study of N-alkyl derivatives of the racemic nor 11 indicated similarities between the interaction of various derivatives with the mu- and delta- but not the kappa 1-opioid receptor. As studies on the molecular basis of the interaction of opioid ligands with their respective receptors continue to gain momentum, the SAR data described herein for the synthetic phenylmorphans will prove useful for further studies.
(PMID: 7739011)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.
Categorized Comment - additional comments and annotations
From BioAssay Depositor:
Assay Type: Binding
Target Type: Target is a single protein chain
Assay Data Source: Scientific Literature
Result Definitions
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TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1IC50*IC50 PubChem standard valueFloatμM
3BEIBinding Efficiency Index(nM)Float
2SEISurface Efficiency Index(nM)Float
4LELigand EfficiencyFloat
5LLELipophilic Ligand EfficiencyFloat
6IC50 activity commentIC50 activity commentString
7IC50 standard flagIC50 standard flagInteger
8IC50 qualifierIC50 qualifierString
9IC50 published valueIC50 published valueFloatnM
10IC50 standard valueIC50 standard valueFloatnM
11IC50 binding domainsIC50 binding domainsString

* Activity Concentration.

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