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

Language
en
Document Type
Article
Issue Date
2019-05-10
Issue Year
2017
Authors
Nebel, Natascha
Strauch, Brigitte
Maschauer, Simone
Lasch, Roman
Rampp, Hannelore
Fehler, Stefanie K.
Bock, Leonard R.
Hübner, Harald
Gmeiner, Peter
Heinrich, Markus R.
Editor
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 [18F]2a was established, together with the radiosynthesis of methyl-, methoxy-, and phenyl-substituted derivatives ([18F]2b–f). With the substituted [18F]fluorophenylazocarbylates in hand, two prototype azocarboxylates radioligands were synthesized by 18F-fluoroarylation, namely the methoxy azocarboxamide [18F]3d as the D3 receptor radioligand and [18F]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.

Journal Title
ACS Omega
Volume
2
Issue
12
Citation
ACS Omega 2.12 (2017): S. 8649–8659. <https://doi.org/10.1021/acsomega.7b01374>
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