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BioAssay: AID 601797

Displacement of [3H]DPDPE from delta opioid receptor in rat brain membranes

In order to slightly modify the orientation of the pharmacophoric structural elements of the potent kappa agonists 7 and 8, the three-membered bridge of these compounds was enlarged to four carbon atoms. Reductive amination of the bicyclic ketone 11 with pyrrolidine and NaBH(OAc)3 provided the pyrrolidine 12 with excellent diastereoselectivity (>99:1). The diastereomeric pyrrolidine 24 was more ..
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 Tested Compounds
 Tested Compounds
All(7)
 
 
Active(2)
 
 
Inconclusive(4)
 
 
Unspecified(1)
 
 
 Tested Substances
 Tested Substances
All(7)
 
 
Active(2)
 
 
Inconclusive(4)
 
 
Unspecified(1)
 
 
 Related BioAssays
 Related BioAssays
AID: 601797
Data Source: ChEMBL (751948)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2012-02-15
Modify Date: 2013-11-17

Data Table ( Complete ):           Active    All
Target
Sequence: RecName: Full=Delta-type opioid receptor; Short=D-OR-1; Short=DOR-1; AltName: Full=Opioid receptor A
Description ..   
Protein Family: Serpentine type 7TM GPCR chemoreceptor Srx
Comment ..   

Gene:OPRD1     Related Protein 3D Structures     More BioActivity Data..
BioActive Compounds: 2
Description:
Title: Synthesis of 7,9-diazabicyclo[4.2.2]decanes as conformationally restricted kappa receptor agonists: fine tuning of the dihedral angle of the ethylenediamine pharmacophore.

Abstract: In order to slightly modify the orientation of the pharmacophoric structural elements of the potent kappa agonists 7 and 8, the three-membered bridge of these compounds was enlarged to four carbon atoms. Reductive amination of the bicyclic ketone 11 with pyrrolidine and NaBH(OAc)3 provided the pyrrolidine 12 with excellent diastereoselectivity (>99:1). The diastereomeric pyrrolidine 24 was established by a stepwise strategy, involving an unselective nucleophilic substitution of the triflate 20 with NaN3 as key step. The synthesis of 9 and 10 was completed by LiAlH4 reduction, replacement of the PMB group at N-9 with a (3,4-dichlorophenyl)acetyl residue and the N-7-benzyl group with the methoxycarbonyl moiety. The kappa receptor affinity of the new compounds is strongly dependent on the stereochemistry and the N-7-substituent. The (1RS,2SR,6SR)-configured pyrrolidine 9 with a methoxycarbonyl moiety at N-7 represents the most potent kappa ligand (Ki=65 nM) of this series. The 65fold lower kappa affinity of 9 compared with its smaller homologue 7 is partly explained by 9 being a racemic mixture, and the slightly modified dihedral angle of the pharmacophoric N(pyrrolidine)-C-C-N(dichlorophenylacetyl) substructure. However, the additional methylene moiety, which enlarges the size of the bridge, is assumed to be responsible for the reduced kappa affinity.
(PMID: 21481987)
Comment
Compounds with activity <= 50uM or explicitly reported as active by ChEMBL are flagged as active in this PubChem assay presentation.

Categorized Comment
ChEMBL Assay Type: Binding

ChEMBL Assay Data Source: Scientific Literature

ChEMBL Target ID: 10526

ChEMBL Target Type: Target is a single protein chain

Result Definitions
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TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1Ki*Ki PubChem standard valueFloatμM
2BEIBinding Efficiency Index(nM)Float
3SEISurface 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
11Ki binding domainsKi binding domainsString

* Activity Concentration.

Data Table (Concise)
Classification
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