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Synthesis, Radiosynthesis and Biological Evaluation of Buprenorphine‐Derived Phenylazocarboxamides as Novel μ‐Opioid Receptor Ligands
Targeted structural modifications have led to a novel type of buprenorphine‐derived opioid receptor ligand displaying an improved selectivity profile for the μ‐OR subtype. On this basis, it is shown that phenylazocarboxamides may serve as useful bioisosteric replacements for the widely occurring cin...
Autores principales: | , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
John Wiley and Sons Inc.
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7383964/ https://www.ncbi.nlm.nih.gov/pubmed/32378310 http://dx.doi.org/10.1002/cmdc.202000180 |
Sumario: | Targeted structural modifications have led to a novel type of buprenorphine‐derived opioid receptor ligand displaying an improved selectivity profile for the μ‐OR subtype. On this basis, it is shown that phenylazocarboxamides may serve as useful bioisosteric replacements for the widely occurring cinnamide units, without loss of OR binding affinity or subtype selectivity. This study further includes functional experiments pointing to weak partial agonist properties of the novel μ‐OR ligands, as well as docking and metabolism experiments. Finally, the unique bifunctional character of phenylazocarboxylates, herein serving as precursors for the azocarboxamide subunit, was exploited to demonstrate the accessibility of an (18)F‐fluorinated analogue. |
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