Abstract
Bifunctional ligands containing an ester linkage between morphine and the δ-selective pharmacophore Dmt-Tic were synthesized, and their binding affinity and functional bioactivity at the μ, δ and κ opioid receptors determined. Bifunctional ligands containing or not a spacer of β-alanine between the two pharmacophores lose the μ agonism deriving from morphine becoming partial μ agonists 4 or μ antagonists 5. Partial κ agonism is evidenced only for compound 4. Finally, both compounds showed potent δ antagonism.
Copyright © 2010 Elsevier Masson SAS. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, N.I.H., Intramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Animals
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CHO Cells
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Cricetinae
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Cricetulus
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Dipeptides / chemical synthesis
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Dipeptides / chemistry
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Dipeptides / pharmacology*
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Esters / chemical synthesis
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Esters / chemistry
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Esters / pharmacology*
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Humans
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Ligands
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Molecular Conformation
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Morphine / chemical synthesis
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Morphine / chemistry
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Morphine / pharmacology*
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Narcotic Antagonists*
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Stereoisomerism
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Structure-Activity Relationship
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Tetrahydroisoquinolines / chemical synthesis
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Tetrahydroisoquinolines / chemistry
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Tetrahydroisoquinolines / pharmacology*
Substances
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2',6'-dimethyltyrosyl-1,2,3,4-tetrahydroisoquinoline-3-carboxylic acid
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Dipeptides
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Esters
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Ligands
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Narcotic Antagonists
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Tetrahydroisoquinolines
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Morphine