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

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MTT3-(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。

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

Objective To design and synthesize 2-substituted-4-aminothieno3,2-d]pyrimidine derivatives and evaluate their in vitro antiproliferative activities.Methods The target compounds w ere synthesized in 6 steps starting from 3-aminothiophene-2-carboxylate,and their antiproliferative activity against H-460 and HT29 cancer cell lines w ere tested by MTT assay,w ith CP-31398 as the positive control.Results and Conclusion Sixteen compounds which had not been reported in literatures were synthesized,and their structures w ere confirmed by 1 H-NMR and MS.Five compounds show ed potent antiproliferative activity,and compound 8n displayed promising activity w hich w as 4-to 5-fold better than CP-31398,respectively.