Synthesis, Radiosynthesis and Biological Evaluation of Buprenorphine-Derived Phenylazocarboxamides as Novel mu-Opioid Receptor Ligands

Krüll J, Fehler S, Hofmann L, Nebel N, Maschauer S, Prante O, Gmeiner P, Lanig H, Hübner H, Heinrich M (2020)

Publication Language: English

Publication Status: Published

Publication Type: Journal article, Original article

Publication year: 2020

Journal

ChemMedChem Wiley

Publisher: WILEY-V C H VERLAG GMBH

DOI: 10.1002/cmdc.202000180

Open Access Link: https://doi.org/10.1002/cmdc.202000180

Abstract

Targeted structural modifications have led to a novel type of buprenorphine-derived opioid receptor ligand displaying an improved selectivity profile for the mu-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 mu-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 F-18-fluorinated analogue.

Authors with CRIS profile

Jasmin Krüll Lehrstuhl für Pharmazeutische Chemie Stefanie Fehler Professur für Pharmazeutische Chemie Laura Hofmann Professur für Pharmazeutische Chemie Natascha Nebel Department of Nuclear Medicine Simone Maschauer Department of Nuclear Medicine Olaf Prante Professur für Molekulare Bildgebung und Radiochemie Peter Gmeiner Lehrstuhl für Pharmazeutische Chemie Harald Lanig Zentralinstitut für Scientific Computing (ZISC) Harald Hübner Lehrstuhl für Pharmazeutische Chemie Markus Heinrich Professur für Pharmazeutische Chemie

Additional Organisation(s)

Zentralinstitut für Scientific Computing (ZISC) Exzellenz-Cluster Engineering of Advanced Materials

How to cite

APA:

Krüll, J., Fehler, S., Hofmann, L., Nebel, N., Maschauer, S., Prante, O.,... Heinrich, M. (2020). Synthesis, Radiosynthesis and Biological Evaluation of Buprenorphine-Derived Phenylazocarboxamides as Novel mu-Opioid Receptor Ligands. ChemMedChem. https://dx.doi.org/10.1002/cmdc.202000180

MLA:

Krüll, Jasmin, et al. "Synthesis, Radiosynthesis and Biological Evaluation of Buprenorphine-Derived Phenylazocarboxamides as Novel mu-Opioid Receptor Ligands." ChemMedChem (2020).

BibTeX: Download