2-取代-4-氨基噻吩并[3,2-d]嘧啶类化合物的合成及抗增殖活性  

Synthesis and antiproliferative activities of novel 2-substituted-4-aminothieno[3,2-d]pyrimidine derivatives

作　　者：姜楠[1] 李婷[1] 陶海燕[1] 宫平[1] 

机构地区：[1]沈阳药科大学基于靶点的药物设计与研究教育部重点实验室,辽宁沈阳110016

出　　处：《沈阳药科大学学报》2012年第11期829-833,846,共6页Journal of Shenyang Pharmaceutical University

基　　金：国家科技重大专项资助项目(No.2011ZX09102-001-006)

摘　　要：目的设计并合成2-取代-4-氨基噻吩并[3,2-d]嘧啶类化合物,评价其体外抗增殖活性。方法以3-氨基-2-噻吩甲酸甲酯为起始原料,经6步反应合成目标化合物;以CP-31398为阳性对照药,采用MTT[3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide]法测定了目标化合物对肿瘤细胞株H-460和HT-29的抗增殖活性。结果与结论合成16个未见文献报道的化合物,其结构经1H-NMR、MS确证;5个化合物显示较好的抗增殖活性,其中,化合物8n活性突出,为CP-31398的4-5倍。Objective To design and synthesize 2-substituted-4-aminothieno [ 3,2-d] pyrimidine derivatives and evaluate their in vitro antiproliferative activities. Methods The target compounds were synthesized in 6 steps starting from 3-aminothiophene-27carboxylate, and their antiproliferative activity against H-460 and HT- 29 cancer cell lines were tested by MTT assay,with CP-31398 as the positive control. Results and Conclu- sion Sixteen compounds which had not been reported in literatures were synthesized, and their structures were confirmed by 1^H-NMR and MS. Five compounds showed potent antiproliferative activity, and compound 8n displayed promising activity which was 4-to 5-fold better than CP-31398, respectively.

关 键 词：合成 2-取代-4-氨基噻吩并[3 2-d]嘧啶类化合物 抗增殖活性 

分 类 号：R914[医药卫生—药物化学]