Opioid bifunctional ligands from morphine and the opioid pharmacophore Dmt-Tic

BALBONI, GIANFRANCO;SALVADORI S;MARCZAK E. D;KNAPP B. I;BIDLACK J. M;LAZARUS L. H;PENG X;SI Y. G;NEUMEYER J. L.

2011-01-01

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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.