Medicinal and radiopharmaceutical chemistry with phenylazocarboxylic esters

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非常适合用于亲核芳香族取代和广泛的进一步转化的试剂。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。

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.