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

ACS Omega
Natascha NebelOlaf Prante

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 significa...Continue Reading

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Citations

Feb 28, 2018·The Journal of Organic Chemistry·Dinesh S BarakSanjay Batra

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Methods Mentioned

BETA
imaging technique
NMR
column chromatography

Software Mentioned

PRISM6
GraphPad

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