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[F]氟苯基偶氮羧酸盐：多巴胺D3和μ-阿片受体潜在放射性配体的设计与合成

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

作者信息

Nebel Natascha, Strauch Brigitte, Maschauer Simone, Lasch Roman, Rampp Hannelore, Fehler Stefanie K, Bock Leonard R, Hübner Harald, Gmeiner Peter, Heinrich Markus R, Prante Olaf

机构信息

Department of Nuclear Medicine, Molecular Imaging and Radiochemistry, Friedrich Alexander University Erlangen-Nürnberg (FAU), Schwabachanlage 6, Erlangen D-91054, Germany.

Department of Chemistry and Pharmacy, Medicinal Chemistry, Emil Fischer Center, Friedrich Alexander University Erlangen-Nürnberg (FAU), Schuhstrasse 19, Erlangen D-91052, Germany.

出版信息

ACS Omega. 2017 Dec 31;2(12):8649-8659. doi: 10.1021/acsomega.7b01374. Epub 2017 Dec 6.

DOI:10.1021/acsomega.7b01374
PMID:29479577
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5819854/
Abstract

F-Labeled building blocks from the type of [F]fluorophenylazocarboxylic--butyl esters offer a rapid, mild, and reliable method for the F-fluoroarylation of biomolecules. Two series of azocarboxamides were synthesized as potential radioligands for dopamine D3 and the μ-opioid receptor, revealing compounds and with single-digit and sub-nanomolar affinity for the D3 receptor and compound 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-[F]fluorophenylazocarboxylic--butyl ester was established, together with the radiosynthesis of methyl-, methoxy-, and phenyl-substituted derivatives (). With the substituted [F]fluorophenylazocarbylates in hand, two prototype azocarboxylates radioligands were synthesized by F-fluoroarylation, namely the methoxy azocarboxamide as the D3 receptor radioligand and as a prototype structure of the μ-opioid receptor radioligand. By introducing the new series of [F]fluorophenylazocarboxylic--butyl esters, the method of F-fluoroarylation was significantly expanded, thereby demonstrating the versatility of F-labeled phenylazocarboxylates for the design of potential radiotracers for positron emission tomography .

摘要

来自[F]氟苯基偶氮羧酸丁酯类型的F标记砌块为生物分子的F-氟芳基化提供了一种快速、温和且可靠的方法。合成了两个系列的偶氮甲酰胺作为多巴胺D3和μ-阿片受体的潜在放射性配体，发现化合物 和 对D3受体具有个位数和亚纳摩尔亲和力，化合物 对μ-阿片受体仅具有微摩尔亲和力，但与先导化合物AH-7921相比，对μ-亚型的选择性增强。建立了一种不使用穴状配体和碱制备4-[F]氟苯基偶氮羧酸丁酯 的“极简程序”，以及甲基、甲氧基和苯基取代衍生物的放射性合成（）。有了取代的[F]氟苯基偶氮基化物后，通过F-氟芳基化合成了两种原型偶氮羧酸盐放射性配体，即作为D3受体放射性配体的甲氧基偶氮甲酰胺 和作为μ-阿片受体放射性配体原型结构的 。通过引入新系列的[F]氟苯基偶氮羧酸丁酯，F-氟芳基化方法得到了显著扩展，从而证明了F标记的苯基偶氮羧酸盐在设计正电子发射断层扫描潜在放射性示踪剂方面的多功能性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b985/6643488/0fe5409835e0/ao-2017-01374f_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b985/6643488/48f760457cd4/ao-2017-01374f_0001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b985/6643488/0fe5409835e0/ao-2017-01374f_0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b985/6643488/48f760457cd4/ao-2017-01374f_0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b985/6643488/dca9b1d4ea60/ao-2017-01374f_0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b985/6643488/e358b241279f/ao-2017-01374f_0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b985/6643488/d3b6b6f49e81/ao-2017-01374f_0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b985/6643488/7fbba215c55e/ao-2017-01374f_0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b985/6643488/0fe5409835e0/ao-2017-01374f_0003.jpg

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