18F]Fluorophenylazocarboxylates: Design and Synthesis of Potential Radioligands for Dopamine D3 and μ-Opioid Receptor

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autor(en): Nebel N, Strauch B, Maschauer S, Lasch R, Rampp H, Fehler S, Bock L, Hübner H, Gmeiner P, Heinrich M, Prante O
Zeitschrift: ACS Omega
Jahr der Veröffentlichung: 2017
Band: 2
Heftnummer: 12
Seitenbereich: 8649-8659
ISSN: 2470-1343


Abstract

18F-Labeled building blocks from the type of [18F]fluorophenylazocarboxylic-tert-butyl esters offer a rapid, mild, and reliable method for the 18F-fluoroarylation of biomolecules. Two series of azocarboxamides were synthesized as potential radioligands for dopamine D3 and the μ-opioid receptor, revealing compounds 3d and 3e with single-digit and sub-nanomolar affinity for the D3 receptor and compound 4c with only micromolar affinity for the μ-opioid receptor, but enhanced selectivity for the μ-subtype in comparison to the lead compound AH-7921. A "minimalist procedure" without the use of a cryptand and base for the preparation of 4-[18F]fluorophenylazocarboxylic-tert-butyl ester [
18
F]2a was established, together with the radiosynthesis of methyl-, methoxy-, and phenyl-substituted derivatives ([
18
F]2b-f). With the substituted [18F]fluorophenylazocarbylates in hand, two prototype azocarboxylates radioligands were synthesized by 18F-fluoroarylation, namely the methoxy azocarboxamide [
18
F]3d as the D3 receptor radioligand and [
18
F]4a as a prototype structure of the μ-opioid receptor radioligand. By introducing the new series of [18F]fluorophenylazocarboxylic-tert-butyl esters, the method of 18F-fluoroarylation was significantly expanded, thereby demonstrating the versatility of 18F-labeled phenylazocarboxylates for the design of potential radiotracers for positron emission tomography .


FAU-Autoren / FAU-Herausgeber

Bock, Leonard
Lehrstuhl für Pharmazeutische Chemie
Fehler, Stefanie
Lehrstuhl für Pharmazeutische Chemie
Gmeiner, Peter Prof. Dr.
Lehrstuhl für Pharmazeutische Chemie
Heinrich, Markus Prof. Dr.
Professur für Pharmazeutische Chemie
Hübner, Harald Dr.
Lehrstuhl für Pharmazeutische Chemie
Lasch, Roman
Lehrstuhl für Pharmazeutische Chemie
Maschauer, Simone PD Dr.
Professur für Molekulare Bildgebung und Radiochemie
Nebel, Natascha
Nuklearmedizinische Klinik
Prante, Olaf Prof. Dr.
Professur für Molekulare Bildgebung und Radiochemie


Zitierweisen

APA:
Nebel, N., Strauch, B., Maschauer, S., Lasch, R., Rampp, H., Fehler, S.,... Prante, O. (2017). 18F]Fluorophenylazocarboxylates: Design and Synthesis of Potential Radioligands for Dopamine D3 and μ-Opioid Receptor. ACS Omega, 2(12), 8649-8659. https://dx.doi.org/10.1021/acsomega.7b01374

MLA:
Nebel, Natascha, et al. "18F]Fluorophenylazocarboxylates: Design and Synthesis of Potential Radioligands for Dopamine D3 and μ-Opioid Receptor." ACS Omega 2.12 (2017): 8649-8659.

BibTeX: 

Zuletzt aktualisiert 2018-23-11 um 10:53