二氢三嗪类化合物的设计、合成及其促葡萄糖消耗活性研究

Design,Synthesis and Glucose Consumption Activity of Dihydrotriazines

以芳香醛和乙酸乙烯酯为原料,经Aldol羟醛缩合反应得到中间体,再与盐酸二甲双胍反应合成一系列新型结构的标题化合物。其结构经1HNMR、13CNMR和HRMS确证。在HepG2细胞模型中对目标化合物进行了促葡萄糖消耗活性测试,结果显示大部分化合物具有一定的促葡萄糖消耗活性。其中,化合物4-氨基-3,6-二氢-2-二甲氨基-6-苯乙烯基-1,3,5-三嗪、4-氨基-3,6-二氢-2-二甲氨基-6-(2,3-二甲氧基)苯乙烯基-1,3,5-三嗪、4-氨基-3,6-二氢-2-二甲氨基-6-(3,4-二甲氧基)苯乙烯基-1,3,5-三嗪、4-氨基-3,6-二氢-2-二甲氨基-6-(2,5-二甲氧基)苯乙烯基-1,3,5-三嗪和4-氨基-3,6-二氢-2-二甲氨基-6-胡椒苯乙烯基-1,3,5-三嗪的促葡萄糖消耗活性较阳性对照药二甲双胍略强或相当,它们具有进一步开发的价值。

Using aromatic aldehydes and vinyl acetate as the starting materials,the key intermediates were synthesized via aldol condensation,which reacted with metformin hydrochloride to afford a novel series of dihydrotriazine derivatives. The structures of the target compounds were confirmed by1 HNMR,13 CNMR and HRMS,and their glucose consumption activity were investigated in human liver cancer Hep G2 cell lines. The results showed that most of the synthesized compounds possessed a certain glucose consumption activity. Among them,4-amino-3,6-dihydro-2-dimethylamino-6-phenylvinyl-1,3,5-triazine,4-amino-3,6-hihydro-2-dimethylamino-6-（2,3-dimethoxyl） phenylvinyl-1,3,5-triazine,4-amino-3,6-dihydro-2-dimethylamino-6-（3,4-dimethoxyl） phenylvinyl-1,3,5-triazine,4-amino-3,6-dihydro-2-dimethylamino-6-（2,5-dimethoxyl） phenylvinyl-1,3,5-triazine and 4-amino-3,6-dihydro-2-dimethylamino-6-piper-onylphenylvinyl-1,3,5-triazine exhibited comparable or more potent activities than the positive control metformin,and thus were worthy of further evaluation.