1, 2, 4-三氮唑类衍生物的设计、合成及SHP-2活性评价

Design and Synthesis of 1, 2, 4-Triazole Derivatives and Evaluation of SHP-2 Activity

摘要: SHP2作为一种重要的磷酸化酶与多种癌症的发生密切相关，高活化的SHP2使得包括胃癌，乳腺癌在内的各种癌症的发生率增大，因此它成为治疗癌症的重要靶标之一。为了寻找高效的SHP2抑制剂，本文在具有潜在的抗肿瘤活性的1, 2, 4-三氮唑母核基础上，通过化学合成，设计并完成了10个新型1, 2, 4-三氮唑类衍生物，利用核磁共振氢谱技术对结构进行了表征，并进行了生物学活性评价，为后期的基于1, 2, 4-三氮唑母核的SHP2抑制剂发现工作奠定了一定的基础。

Abstract: SHP2 is closely associated with the development of many cancers as a key phosphatase. Highly activated SHP2 is one of the important targets for cancer treatment as it increases the incidence of several cancers, including gastric and breast cancer. In order to find efficient SHP2 inhibitors, in this work, based on the 1, 2, 4-triazole parent nucleus with potential antitumour activity, ten novel 1, 2, 4-triazole derivatives were designed and completed by chemical synthesis. The structures were characterised by NMR hydrogen spectroscopy and evaluated for biological activity, which laid a certain foundation for the later discovery of SHP2 inhibitors based on the parent nucleus of 1, 2, 4-triazole.