3-取代-4-氧-3H-咪唑并[5,1-d][1,2,3,5]四嗪-8-羧酸衍生物的合成及其抗癌活性研究(英文)

Synthesis and Antitumour Activities of 3-Substituted 4-Oxo-3H-imidazo tetrazine-8-carboxylic Acids and Their Derivatives

根据咪唑四嗪酮类抗癌药物构效关系研究结果 ,以替莫唑胺和米托唑胺为先导化合物 ,设计合成了 1 0个 3 取代 4 氧 3H 咪唑并 [5 ,1 d][1 ,2 ,3 ,5 ]四嗪 8 羧酸及其衍生物。以 4 氨基咪唑 5 甲酰胺盐酸盐为起始原料 ,经酰化、重氮化环合得到咪唑四嗪酮环 ,再经 3位和 8位官能团转化 ,得到目标化合物。其中 5个目标化合物未见文献报道 ,其结构均经红外光谱、核磁共振氢谱和元素分析等数据证实。经体外抗癌活性筛选 ,3个化合物表现出良好的抗癌活性。

Based on the antitumour mechanism of temozolomide and the SAR study result of imidazotetrazinone antitumour drugs,3-substituted 4-oxo-3H-imidazotetrazine- 8-carboxylic acids and their derivatives were designed and synthesized.Nitrosation cyclisation of 5-amino-1-carbamoylimidazole-4-carboxamides afforded 3-substituted 4-oxo-3H-imidazo tetrazine-8-carboxamide.The facile conversion of 3- or 8- functional groups gave other imidazotetrazinones.Of the ten target compounds,five were novel compounds,of which the chemical structures were characterized by the applications of elemental analysis,IR, 1H-NMR, 13 C-NMR and MS.The chemical entities were tested against GM 892A cell (Mer -) and Raji cell (Mer +) and three compounds had significant antitumour activities.