%0 Journal Article
%T 吡嗪类SHP2抑制剂的设计、合成及生物活性评价<br>Design, Synthesis and Biological Activity Evaluation of Pyrazine SHP2 Inhibitors
%A 陈卓
%A 堵桐弘
%A 吕遐师
%A 李沛峰
%A 赖宜生
%J Hans Journal of Medicinal Chemistry
%P 175-184
%@ 2331-8295
%D 2024
%I Hans Publishing
%R 10.12677/hjmce.2024.123020
%X SHP2是一个肿瘤治疗的潜在靶点。本文以TNO155为先导化合物，采用基于片段的药物设计策略，设计并合成三个系列共11个新型吡嗪类SHP2变构抑制剂，其结构均经<sup>1</sup>H-NMR和ESI-MS谱确证。采用荧光分析方法，通过替代底物DiFMUP的去磷酸化程度对目标化合物开展体外活性评价。结果表明，目标化合物对SHP2蛋白显示不同程度的抑制活性。其中2个化合物C-2和C-3的活性较为突出，值得进一步研究。<br />
Eleven novel pyrazine SHP2 allosteric inhibitors were designed and synthesized in three series based on TNO155 of Novartis, drug design strategy based on fragments and molecular docking technology of computer-aided drug design. Their structures were confirmed by <sup>1</sup>H-NMR and ESI-MS spectra. The <i>in vitro</i> activity of DiFMUP was evaluated by fluorescence analysis. The results showed that the target compounds showed different degrees of inhibitory activity on SHP2. Among them, two compounds, C-2 and C-3, have outstanding activity and deserve further study.
%K 蛋白酪氨酸磷酸酶，SHP2抑制剂，TNO155，生物活性<br>Protein Tyrosine Phosphatase
%K SHP2 Inhibitor
%K TNO155
%K Biological Activity
%U http://www.hanspub.org/journal/PaperInformation.aspx?PaperID=92761