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BioAssay: AID 272398

Activity at human dopamine D4.4 receptor expressed in HEK293 cells assessed as inhibition of forskolin-stimulated cAMP production

We report the synthesis of trans-2,3-dihydroxy-6a,7,8,12b-tetrahydro-6H-chromeno[3,4-c]isoquinoline hydrochloride 6 and the resolution of its enantiomers. This new compound is an oxygen bioisostere of the potent dopamine D1-selective full agonist dihydrexidine. The initial synthetic approach involved, as a key step, a Suzuki coupling between a chromene triflate and a boronate ester, followed by more ..
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 Tested Compounds
 Tested Compounds
All(9)
 
 
Active(7)
 
 
Inconclusive(2)
 
 
 Tested Substances
 Tested Substances
All(9)
 
 
Active(7)
 
 
Inconclusive(2)
 
 
 Related BioAssays
 Related BioAssays
AID: 272398
Data Source: ChEMBL (410545)
Depositor Category: Literature, Extracted
BioAssay Version:
Deposit Date: 2010-05-25
Modify Date: 2013-11-18

Data Table ( Complete ):           Active    All
Target
Sequence: RecName: Full=D(4) dopamine receptor; AltName: Full=D(2C) dopamine receptor; AltName: Full=Dopamine D4 receptor
Description ..   
Protein Family: FAM101 family
Comment ..   

Gene:DRD4     Related Protein 3D Structures     More BioActivity Data..
BioActive Compounds: 7
Description:
Title: trans-2,3-dihydroxy-6a,7,8,12b-tetrahydro-6H-chromeno[3,4-c]isoquinoline: synthesis, resolution, and preliminary pharmacological characterization of a new dopamine D1 receptor full agonist.

Abstract: We report the synthesis of trans-2,3-dihydroxy-6a,7,8,12b-tetrahydro-6H-chromeno[3,4-c]isoquinoline hydrochloride 6 and the resolution of its enantiomers. This new compound is an oxygen bioisostere of the potent dopamine D1-selective full agonist dihydrexidine. The initial synthetic approach involved, as a key step, a Suzuki coupling between a chromene triflate and a boronate ester, followed by isoquinoline formation and reduction of the resulting isoquinoline. Subsequently, a more efficient route was developed that involved conjugate addition of an aryl Grignard reagent to a 2-nitrochromene. The title compound possessed high affinity (Ki=20-30 nM) for porcine D1-like receptors in native striatal tissue and full intrinsic activity at cloned human dopamine D1 receptors but had much lower affinity at dopamine D2-like receptors (Ki=3000 nM). The binding and functional properties of this compound illustrate again the utility of constructing dopamine D1 agonist ligands around the beta-phenyldopamine pharmacophore template.
(PMID: 17154515)
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: Functional

ChEMBL Assay Data Source: Scientific Literature

ChEMBL Assay Cell Type: HEK293

ChEMBL Target ID: 90

ChEMBL Target Type: Target is a single protein chain

Result Definitions
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TIDNameDescriptionHistogramTypeUnit
OutcomeThe BioAssay activity outcomeOutcome
1EC50*EC50 PubChem standard valueFloatμM
2Activity activity commentActivity activity commentString
3Activity standard flagActivity standard flagInteger
4Activity qualifierActivity qualifierString
5Activity published valueActivity published valueFloat
6Activity standard valueActivity standard valueFloat
7Activity binding domainsActivity binding domainsString
8EC50 activity commentEC50 activity commentString
9EC50 standard flagEC50 standard flagInteger
10EC50 qualifierEC50 qualifierString
11EC50 published valueEC50 published valueFloatnM
12EC50 standard valueEC50 standard valueFloatnM
13EC50 binding domainsEC50 binding domainsString

* Activity Concentration.

Data Table (Concise)
Classification
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