氨基噻吩取代的TAE-226类似物合成与生物活性研究  

Synthesis and Biological Activity of TAE-226 Analogues Substituted with Aminothiophene

作　　者：王庆涛 饶念 韦广胜 徐应 乐意[1] 刘力[1] 鄢龙家 WANG Qing-tao;RAO Nian;WEI Guang-sheng;XU Ying;LE Yi;LIU Li;YAN Long-jia(School of Pharmaceutical Sciences,Guizhou University,Guiyang 550025,China)

机构地区：[1]贵州大学药学院,贵州贵阳550025

出　　处：《化学试剂》2023年第12期118-125,共8页Chemical Reagents

基　　金：贵州省科技计划项目(黔科合基础-ZK[2022]一般124)。

摘　　要：黏着斑激酶(Focal Adhesion Kinase,FAK)是一种非受体酪氨酸激酶,在胶质瘤中存在过表达现象。因此,以FAK为靶点开发治疗胶质瘤的药物引起了广泛研究兴趣。以TAE-226为先导化合物,利用生物电子等排原理设计并合成了21个含2-氨基噻吩片段的三嗪类化合物作为新型FAK抑制剂。所有的目标化合物结构经^(1)HNMR、^(13)CNMR和HRMS确证。随后,采用MTT法评价了该系列化合物对人脑恶性星形胶质母瘤细胞U87-MG的体外抗肿瘤活性。结果表明,部分化合物表现出较好的抗肿瘤活性,特别是2-((4-氯-6-((4-(4-(2-羟乙基)哌嗪-1-基)苯基)氨基)-1,3,5-三嗪-2-基)氨基)-N-甲基噻吩-3-甲酰胺活性显著优于阳性对照TAE-226,其IC 50值为1.791μmol/L。Focal adhesion kinase(FAK)is a non-receptor tyrosine kinase,which is overexpressed in gliomas.Therefore,the development of drugs targeting FAK for the treatment of glioma has attracted widespread research interest.In this paper,with TAE-226 as the lead compound,21 triazines containing 2-aminothiophene fragments were designed and synthesized as new FAK inhibitors based on the principle of bioelectronic isoarrangement.The structures of all target compounds were confirmed by^(1)HNMR,^(13)CNMR,and HRMS.Subsequently,the in vitro anti-tumor activities of these compounds against human brain malignant astroblastoma cell U87-MG in vitro were evaluated by MTT method.The results showed that some compounds exhibited good anti-tumor activity,especially 2-((4-((4-([1,4′-bipiperidin]-1′-yl)phenyl)amino)-6-chloro-1,3,5-triazin-2-yl)amino)-N-methylthiophene-3-carboxamide,which had significantly better activity than the positive control TAE-226,with an IC 50 value of 1.791μmol/L.

关 键 词：氨基 噻吩 三嗪 抗肿瘤 胶质瘤 

分 类 号：R739.91[医药卫生—肿瘤]