Pharmaceutical Institute, Pharmaceutical Chemistry I, University of Bonn, An der Immenburg 4, 53121, Bonn, Germany.
Molecular Pharmacology Section, National Cancer Institute, NIH, Bethesda, MD, 20892, USA.
ChemMedChem. 2018 Oct 8;13(19):2080-2089. doi: 10.1002/cmdc.201800263. Epub 2018 Sep 6.
The introduction of fluorine into bioactive molecules is a matter of importance in medicinal chemistry. In this study, representatives of various chemical entities of fluoroaromatic compounds were synthesized. Depending on the reaction conditions, either tetrafluorophthalimides or ammonium tetrafluorophthalamates are accessible from tetrafluorophthalic anhydride and primary amines. Tetrafluorophthalamic acids undergo thermal decarboxylation to yield tetrafluorobenzamides. These could be successfully converted upon treatment with primary amines, in the course of an aromatic nucleophilic substitution, to 2,3,5-trifluorobenzamides with respective amino substituents at the 4-position. The five structure types were characterized by means of spectroscopic and crystallographic methods. The synthesized compounds were evaluated as inhibitors of angiogenesis by measuring microvessel outgrowth in a rat aortic ring assay. The biological activity was maintained throughout these different polyfluorinated chemotypes.
将氟原子引入生物活性分子在药物化学中是一个重要的问题。在这项研究中，合成了各种氟化芳香族化合物的化学实体的代表物。根据反应条件，四氟邻苯二甲酰亚胺或四氟邻苯二甲酰胺盐可由四氟邻苯二甲酸酐和伯胺制得。四氟邻苯二甲酸受热脱羧生成四氟苯甲酰胺。这些化合物在与伯胺反应时，通过芳香亲核取代反应，在 4 位上带有相应的氨基取代基，可成功转化为 2,3,5-三氟苯甲酰胺。这五种结构类型通过光谱和晶体学方法进行了表征。通过测量大鼠主动脉环试验中的微血管生长，评估了合成化合物作为血管生成抑制剂的活性。在这些不同的多氟化化学类型中，生物活性都得到了保持。
