Synthesis, biological evaluation and radiosynthesis of buprenorphine-derived phenylazocarboxamides as novel μ-opioid receptor ligands.

Synthesis, biological evaluation and radiosynthesis of buprenorphine-derived phenylazocarboxamides as novel μ-opioid receptor ligands.
ChemMedChem. 2020 May 06;:
Authors: Krüll J, Fehler SK, Hofmann L, Nebel N, Maschauer S, Prante O, Gmeiner P, Lanig H, Hübner H, Heinrich MR
Abstract
Targeted structural modifications led to a novel type of buprenorphine-derived opioid receptor ligands 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 widely occuring cinnamide units, without loss of OR binding affinity or subtype selectivity. The present 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-fluorinated analogue.
PMID: 32378310 [PubMed - as supplied by publisher]

Source: ChemMedChem - May 5, 2020 Category: Chemistry Authors: Krüll J, Fehler SK, Hofmann L, Nebel N, Maschauer S, Prante O, Gmeiner P, Lanig H, Hübner H, Heinrich MR Tags: ChemMedChem Source Type: research