Medicinal and radiopharmaceutical chemistry with phenylazocarboxylic esters

苯基偶氮甲酸酯的药物和放射性药物化学

• 批准号: 104754872
• 负责人: Professor Dr. Markus Heinrich
• 金额: --
• 依托单位: Nuklearmedizinische Klinik
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2009
• 资助国家: 德国
• 起止时间: 2008-12-31 至 2018-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/104754872?language=en
• 关键词: Medicinal; radiopharmaceutical; chemistry; phenylazocarboxylic; esters

Within our preliminary work we have been able to demonstrate that phenylazocarboxylic acid esters can be well suited reagents for nucleophilic aromatic substitutions and a wide range of further transformations. Based on our current results two fields of application in medicinal chemistry appear especially attractive, which we would now like to investigate in more detail. In the first subproject, phenylazocarboxylates shall be evaluated with regard to an application in combinatorial synthesis, which plays a key role in todays drug development. After a nucleophilic aromatic substitution as a first step, which is already known to be feasible under mild conditions and with high selectivity, diverse further transformations shall be conducted with the azocarbonyl unit as central reactive moiety. The aim hereby is to establish phenylazocarboxylates as highly versatile bifunctional reagents. The research planned within the second subproject is based on the key observation that phenylazocarboxylates can be radioactively labeled with [18F]fluoride ions in less than one minute and with high yields. The new methodologies developed in the first subproject shall then be used for the straightforward and efficient synthesis of new radioligands for PET studies.

在我们的初步工作中，我们已经能够证明，苯基偶氮羧酸酯可以很好地适合试剂的亲核芳族取代和广泛的进一步转化。根据我们目前的研究结果，药物化学中的两个应用领域显得特别有吸引力，我们现在想更详细地研究。在第一个子项目中，将评估苯偶氮羧酸酯在组合合成中的应用，这在当今的药物开发中起着关键作用。在作为第一步的亲核芳族取代（其已知在温和条件下以高选择性是可行的）之后，将以偶氮羰基单元作为中心反应性部分进行各种进一步的转化。本发明的目的是建立作为高度通用的双功能试剂的苯基偶氮羧酸酯。第二个子项目中计划的研究是基于以下关键观察结果，即苯偶氮羧酸盐可以在不到一分钟的时间内用[18F]氟离子进行放射性标记，并且产率很高。第一个子项目中开发的新方法将用于直接有效地合成PET研究所需的新放射性配体。

项目成果

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

[18F]氟苯基偶氮甲酸盐：多巴胺 D3 和 Î⁄-阿片受体的潜在放射性配体的设计和合成

• DOI: 10.1021/acsomega.7b01374
• 发表时间: 2017
• 期刊: ACS Omega
• 影响因子: 4.1
• 作者: N. Nebel;B. Strauch;S. Maschauer;R. Lasch;H. Rampp;S. K. Fehler;L. R. Bock;H. Hübner;P. Gmeiner;M. R. Heinrich;O. Prante
• 通讯作者: O. Prante

Microwave-Assisted Rapid One-Pot Synthesis of Fused and Non-Fused Indoles and 5-[18 F]Fluoroindoles from Phenylazocarboxylates.

• DOI: 10.1002/chem.201703890
• 发表时间: 2017-11
• 期刊: Chemistry
• 作者: Jasmin Krüll;A. Hubert;N. Nebel;O. Prante;M. Heinrich

Selective Functionalization of Graphene at Defect-Activated Sites by Arylazocarboxylic tert-Butyl Esters.

芳基偶甲酸叔丁酯在缺陷激活位点选择性官能化石墨烯

• DOI: 10.1002/anie.201811192
• 发表时间: 2019
• 期刊: Angewandte Chemie
• 作者: C. E. Halbig;R. Lasch;J. Krüll;A. Pirzer;Z. Wang;J. N. Kirchhof;K. I. Bolotin;M. R. Heinrich;S. Eigler
• 通讯作者: S. Eigler

Zinc-Mediated Allylation and Benzylation of Phenylazocarboxylic Esters.

锌介导的苯基偶氮甲酸酯的烯丙基化和苯甲基化

• DOI: 10.1021/acs.joc.5b01978
• 发表时间: 2015
• 期刊: The Journal of organic chemistry
• 作者: R. Lasch;M. R. Heinrich
• 通讯作者: M. R. Heinrich

Optimization and synthesis of an (18) F-labeled dopamine D3 receptor ligand using [(18) F]fluorophenylazocarboxylic tert-butylester.

• DOI: 10.1002/jlcr.3361
• 发表时间: 2016-02
• 期刊: Journal of labelled compounds & radiopharmaceuticals
• 影响因子: 1.8
• 作者: N. Nebel;S. Maschauer;C. Hocke;H. Hübner;P. Gmeiner;O. Prante