3-苯并咪唑-6-(3,5-二甲氧基苯基)吲唑类FGFR抑制剂的合成及活性研究

目的 寻找具有新型骨架结构的成纤维细胞生长因子受体(FGFR)抑制剂.方法 基于活性化合物1和2的结构,利用“杂交”设计原理,设计并合成了一系列3-苯并咪唑-6-(3,5-二甲氧基苯基)吲唑类衍生物.结果 目标化合物经1 HNMR和质谱确证结构,并评价了其对人胃癌细胞SNU-16的增殖抑制活性.结论 该系列化合物均对FGFR高表达的肿瘤细胞有较好的增殖抑制活性,其中,化合物3g的IC50值达到0.32 μmol·L-1.3-苯并咪唑-6-(3,5-二甲氧基苯基)吲唑是一类新型的FGFR抑制剂骨架,值得进一步结构修饰研究.

Synthesis and antiproliferative activity of 3-benzoimidazol-6-(3,5-dimethoxyphenyl)-indazoles as FGFR inhibitors

OBJECTIVE To discover FGFR inhibitors with novel scaffolds.METHODS Based on the structures of compounds 1 and 2,their hybrid derivatives,3-benzoimidazol-6-(3,5-dimethoxyphenyl)-indazoles,were designed and synthesized.RESULTS The structures of target compounds were confirmed by 1HNMR and MS,and their proliferative effect against FGFR2-amplified human gastric cancer cell line SNU-16 was evaluated.CONCLUSION Most of the new compounds exhibit good antiprolif erative activity.Compound 3g possesses an IC50 value of 0.32 μmol· L-1.The result indicates that 3-benzoimidazol-6-(3,5-dimethoxyphenyl)-indazole is a novel scaffold for FGFR inhibitor and deserves further exploration.