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
Synthesis and antiproliferative activity of 3-benzoimidazol-6-( 3,5-dimethoxyphenyl)-indazoles as FGFR inhibitors
作者：严伟;段文虎;
Author：
收稿日期： 年卷（期）页码：2017,32(02):-120-123
期刊名称：华西药学杂志
Journal Name：WEST CHINA JOURNAL OF PHARMACEUTICAL SCIENCES
关键字：抗肿瘤药物;3-苯并咪唑-6-(3,5-二甲氧基苯基)吲唑;FGFR抑制剂;结构修饰
Key words：
基金项目：
中文摘要
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~1HNMR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IC_(50)值达到0.32μmol·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。
参考文献
[1]Brooks AN,Kilgour E,Smith PD.Molecular pathways:Fibroblast growth factor signaling:A new therapeutic opportunity in cancer[J].Clin Cancer Res,2012,18(7):1855-1862.
[2]Dillon C,Spencer-Dene B,Dickson C.A crucial role for fibroblast growth factor signaling in embryonic mammary gland development[J].J Mammary Gland Biol Neoplasia,2004,9(2):207-215.
[3]Marek L,Ware KE,Fritzsche A,et al.Fibroblast growth factor(FGF)and FGF receptor-mediated autocrine signaling in non-small-cell lung cancer cells[J].Mol Pharmacol,2009,75(1):196-207.
[4]Kwabi-Addo B,Ozen M,Ittmann M.The role of fibroblast growth factors and their receptors in prostate cancer[J].Endocr Relat Cancer,2004,11(4):709-724.
[5]Katoh M.Cancer genomics and genetics of FGFR2(Review)[J].Int J Oncol,2008,33:233-237.
[6]Korc M,Friesel R.The role of fibroblast growth factors in tumor growth[J].Curr Cancer Drug Targets,2009,9(5):639-651.
[7]Mc Bride CM,Renhowe PA,Heise C,et al.Design and structureactivity relationship of 3-benzimidazol-2-yl-1H-indazoles as inhibitors of receptor tyrosine kinases[J].Bioorg Med Chem Lett,2006,16(13):3595-3599.
[8]Gavine PR,Mooney L,Kilgour E,et al.AZD4547:An orally bioavailable,potent,and selective inhibitor of the fibroblast growth factor receptor tyrosine kinase family[J].Cancer Res,2012,72(8):2045-2056.
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