N-3，4，6，7-四氢-2H-取代嘧啶并[1，6-c]喹唑啉-2-烯胺类衍生物的合成及其体外抗肿瘤活性研究

目的合成N-3,4,6,7-四氢-2H-取代嘧啶并1,6-c]喹唑啉-2-烯胺类衍生物,并对其进行体外抗肿瘤活性研究。方法以4,6-二氯嘧啶和6-氨基-1,4-苯并二氧杂环为起始原料,经过氨化、Suzuki偶联、缩合反应和环合反应合成一系列N-3,4,6,7-四氢-2H-取代嘧啶并1,6-c]喹唑啉-2-烯胺类化合物,并采用MTT法对其体外肿瘤活性进行研究。结果设计并合成了18个目标化合物,结构经~1H-NMR和MS确证。活性测试结果显示多个目标化合物抗肿瘤活性与阳性对照药索拉非尼相近。结论发现了一类全新结构的骨架分子,目标化合物具有较强的抗肿瘤活性,为新型抗肿瘤化合物的设计与合成提供思路。

Synthesis of N-3,4,6,7-tetrahydro-2H-pyrimido [1,6-c]quinazolin-2-imine derivatives and their antitumor activities in vitro

Objective To synthesize N-3,4,6,7-tetrahydro-2H-pyrimido1,6-c]quinazolin-2-imine derivatives, and to investigate their antitumor activities in vitro. Methods 2,6-Dichloropyrimidine and 6-amino-1,4-benzodioxole were used as starting materials to synthesize a series of 3,4,6,7-tetrahydro-2H-pyrimido1,6-c]quinazolin-2-imine derivatives through amination, Suzuki couple reaction, condensation, and cyclization reaction. The antitumor activities in vitro were determined by MTT assay. Results Eighteen target compounds were designed and synthesized, and their chemical structures were confirmed by ¹H-NMR and MS. Antitumor activities test showed that some target compounds have as the same antitumor activities as sorafenib. Conclusion A novel skeleton molecular are discovered, and the targeted compounds have good antitumor activities, which offer new mentality to designe and synthesize novel antitumor compounds in the future.