Focal adhesion kinase (FAK) is considered a promising target for the diagnosis and treatment of cancer. In this work, a series of N,N’-(4-((5-bromo-2-(phenylamino)pyrimidin-4-yl)amino)-1,3-phenylene)diacetamide derivatives were synthesized and evaluated as FAK inhibitors and radiotracers. The studied compounds, possessing the same phenylene-diacetamide chain, exhibited high to moderate enzyme inhibition values (IC₅₀) ranging from 3.7 to 108.0 nM. Compound 13a, which exhibits high FAK enzyme inhibition with an IC₅₀ value of 3.7, could effectively suppress the tumor growth. Furthermore, three compounds were radiolabeled with F-18. Among them, a higher tumor uptake value was observed for [¹⁸F]17 (3.73 ± 0.10% ID/g) and [¹⁸F]13a (3.66 ± 0.02% ID/g). Compound [¹⁸F]18 displayed the highest tumor/blood (35.75) value at 120 min postinjection. In addition, the results from docking studies revealed the binding mechanism of the studied compounds. The findings of this study may provide useful guidance to improve the development of radiotracers and enzyme inhibitors.

中文翻译：

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作为 FAK 抑制剂和肿瘤放射性示踪剂的 4-芳氨基嘧啶衍生物的设计、合成和生物学评价

粘着斑激酶（FAK）被认为是癌症诊断和治疗的有希望的靶点。在这项工作中，合成了一系列N , N '-(4-((5-bromo-2-(phenylamino)pyrimidin-4-yl)amino)-1,3-phenylene)二乙酰胺衍生物并作为 FAK 抑制剂进行了评估。和放射性示踪剂。所研究的化合物具有相同的苯二乙酰胺链，表现出高至中等的酶抑制值 (IC ₅₀ )，范围为 3.7 至 108.0 nM。化合物13a具有高FAK酶抑制作用，IC ₅₀值为3.7，可有效抑制肿瘤生长。此外，用 F-18 对三种化合物进行了放射性标记。其中，观察到较高的肿瘤摄取值 [ ¹⁸F] 17 (3.73 ± 0.10% ID/g) 和 [ ¹⁸ F] 13a (3.66 ± 0.02% ID/g)。化合物[ ¹⁸ F] 18在注射后120分钟显示出最高的肿瘤/血液(35.75)值。此外，对接研究的结果揭示了所研究化合物的结合机制。这项研究的结果可能为改进放射性示踪剂和酶抑制剂的开发提供有用的指导。