Synthesis, Structural Characterization, and Antiangiogenic Activity of Polyfluorinated Benzamides.
Synthesis, Structural Characterization, and Antiangiogenic Activity of Polyfluorinated Benzamides.
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多氟苯甲酰胺的合成、结构表征和抗血管生成活性。
DOI：
10.1002/cmdc.201800263
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发表时间：
2018
期刊：
影响因子：
3.4
通讯作者：
Gütschow,Michael
中科院分区：
文献类型：
--
作者：
Steinebach,Christian;Ambrożak,Agnieszka;Dosa,Stefan;Beedie,ShaunnaL;Strope,JonathanD;Schnakenburg,Gregor;Figg,WilliamD;Gütschow,Michael
将氟引入生物活性分子是药物化学中的一个重要问题。在这项研究中，各种化学实体的氟代芳香族化合物的代表进行了合成。根据反应条件，四氟邻苯二甲酰亚胺或四氟邻苯二甲酸铵可由四氟邻苯二甲酸酐和伯胺获得。四氟邻苯二甲酰胺酸经历热脱羧以产生四氟苯甲酰胺。在芳族亲核取代过程中，这些可以在用伯胺处理后成功地转化为在4位具有相应氨基取代基的2，3，5-三氟苯甲酰胺。通过光谱和晶体学方法对这五种结构类型进行了表征。通过在大鼠主动脉环测定中测量微血管生长来评估合成的化合物作为血管生成抑制剂。在这些不同的多氟化化学型中保持生物活性。
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.