以均三嗪为核心的三类新型多杂环分子的合成与生物活性

发布时间：2018-04-12 07:38

本文选题：均三嗪 + -三唑　；参考：《有机化学》2017年08期

【摘要】：均三嗪衍生物具有优良的生物活性,在均三嗪结构中将其它杂环对接引入已成为创制新型药物分子的重要方法.首次将1,2,4-三唑、三唑并噻二唑和1,2,4-三嗪等药效基团拼合在均三嗪结构中,设计合成了三类21个新型目标分子,并通过IR、1H NMR和HRMS等对目标分子进行了结构表征.首先为研究不同取代基团对药效活性的影响,利用4种不同的三嗪单取代化合物分别与含有苯基和正戊基的中间体缩合,合成了8个含有双1,2,4-三唑的目标分子,同时针对三唑环上的氨基进行修饰得到目标产物;其次利用7种不同的三嗪双取代化合物,首次将1,2,4-三嗪和三唑并噻二唑构筑在9个目标分子中.评价了21个目标分子对Cdc25B抑制活性.结果发现13个目标分子对Cdc25B均表现出良好的抑制活性,IC_(50)值在(3.99±0.80)~(0.44±0.07)μg/m L之间,其中6个目标分子的IC_(50)值均低于阳性参照物Na_3VO_4,有望成为潜在的抗肿瘤药物.
[Abstract]:Due to its excellent biological activity, the introduction of other heterocyclic docking into the structure of m-triazine has become an important method for the preparation of novel drug molecules.For the first time, three kinds of 21 novel target molecules were designed and synthesized, and the target molecules were characterized by IR 1H NMR and HRMS, etc. The pharmacokinetic groups such as 1'2'2'4 '-triazole, 1' 2'2 '-thiadiazole and 1' 2'2'2'4''-triazine were assembled into the structure of homotriazine for the first time, and the structure of the target molecule was characterized by IR 1H NMR and HRMS.Firstly, in order to study the effect of different substituents on the pharmacodynamics, eight target molecules containing bis-1m2O4-triazole were synthesized by condensation of four different triazine monosubstituted compounds with phenyl and n-pentyl intermediates, respectively.At the same time, the target product was obtained by modifying the amino group on the triazole ring. Secondly, seven different triazine disubstituted compounds were used to construct 1za2n2-triazine and triazo-thiadiazole into 9 target molecules for the first time.The inhibitory activity of 21 target molecules to Cdc25B was evaluated.The results showed that all the 13 target molecules showed good inhibitory activity to Cdc25B. The values of ICS-50) were between 3.99 卤0.80 渭 g / mL and 0.44 卤0.07 渭 g / mL, and the ICS50 values of 6 target molecules were all lower than those of Na3VO4, which might be a potential antitumor drug.
【作者单位】：辽宁师范大学化学化工学院;
【基金】：辽宁省教育厅科学技术研究(No.2009A426)资助项目~~
【分类号】：O626;TQ460.1

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