Abstract
A series of new 1,4-disubstituted triazoles was prepared from appropriate arylacetylenes and aminoalkylazides using click chemistry methodology. These compounds were evaluated as potential ligands on several subtypes of dopamine receptors in in vitro competition assays, showing high affinity for dopamine D3 receptors, lower affinity for D2 and D4, and no affinity for the D1 receptors. Compound 18 displayed the highest affinity at the D3 receptor with a Ki value of 2.7 nM, selectivity over D2 (70-fold) and D4 (200-fold), and behaviour as a competitive antagonist in the low nanomolar range.
Keywords:
1,2,3-Triazoles; Binding assays; Click chemistry; Dopamine receptors; Microwaves; Synthesis.
Copyright © 2013 Elsevier Ltd. All rights reserved.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Click Chemistry
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Dopamine D2 Receptor Antagonists
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Humans
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Kinetics
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Ligands*
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Piperazines / chemical synthesis*
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Piperazines / chemistry
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Piperazines / metabolism
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Protein Binding
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Receptors, Dopamine D1 / agonists
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Receptors, Dopamine D1 / antagonists & inhibitors
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Receptors, Dopamine D1 / metabolism
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Receptors, Dopamine D2 / agonists
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Receptors, Dopamine D2 / metabolism
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Receptors, Dopamine D3 / agonists
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Receptors, Dopamine D3 / antagonists & inhibitors
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Receptors, Dopamine D3 / chemistry
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Receptors, Dopamine D3 / metabolism*
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Triazoles / chemical synthesis
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Triazoles / chemistry*
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Triazoles / metabolism
Substances
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Dopamine D2 Receptor Antagonists
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Ligands
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Piperazines
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Receptors, Dopamine D1
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Receptors, Dopamine D2
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Receptors, Dopamine D3
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Triazoles