Premium
Synthesis, Radiosynthesis and Biological Evaluation of Buprenorphine‐Derived Phenylazocarboxamides as Novel μ‐Opioid Receptor Ligands
Author(s) -
Krüll Jasmin,
Fehler Stefanie K.,
Hofmann Laura,
Nebel Natascha,
Maschauer Simone,
Prante Olaf,
Gmeiner Peter,
Lanig Harald,
Hübner Harald,
Heinrich Markus R.
Publication year - 2020
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.202000180
Subject(s) - radiosynthesis , chemistry , buprenorphine , selectivity , agonist , bifunctional , ligand (biochemistry) , docking (animal) , partial agonist , combinatorial chemistry , stereochemistry , opioid , opioid receptor , receptor , biochemistry , biology , neuroscience , positron emission tomography , medicine , nursing , catalysis
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.