Abstract
Position 6 of the morphinan skeleton plays a key role in the μ-opioid receptor (MOR) activity in vitro and in vivo. We describe the consequence of the 6-carbonyl group deletion in N-methylmorphinan-6-ones 1-4 on ligand-MOR interaction, signaling, and antinociception. While 6-desoxo compounds 1a, 2a, and 4a show similar profiles to their 6-keto counterparts, the 6-desoxo-14-benzyloxy substituted 3a displays significantly increased MOR binding and agonist potency and a distinct binding mode compared with its analogue 3.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Analgesics / chemical synthesis
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Analgesics / pharmacology*
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Animals
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CHO Cells
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Cell Membrane / physiology
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Cricetulus
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Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / pharmacology
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Guanosine 5'-O-(3-Thiotriphosphate) / physiology
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Ligands
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Molecular Docking Simulation
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Morphinans / chemical synthesis
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Morphinans / pharmacology*
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Receptors, Opioid, delta / agonists
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Receptors, Opioid, kappa / agonists
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Receptors, Opioid, mu / agonists*
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Receptors, Opioid, mu / chemistry
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Receptors, Opioid, mu / metabolism
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Structure-Activity Relationship
Substances
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Analgesics
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Ligands
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Morphinans
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Receptors, Opioid, delta
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Receptors, Opioid, kappa
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Receptors, Opioid, mu
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Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
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Guanosine 5'-O-(3-Thiotriphosphate)