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噻吩并[2,3-d]嘧啶-4(3H)-酮衍生物的合成及其活性研究
刘飞泽
Subtype硕士
Thesis Advisor黄国正、侯雪玲
2018-06-03
Degree Grantor中国科学院大学
Place of Conferral北京
Degree Discipline有机化学
Keyword噻吩并嘧啶类衍生物 合成 抗肿瘤活性 抗流感活性
Abstract

噻吩并嘧啶类衍生物是一类具有良好生物活性的氮杂环化合物,对其合成的新方法和药物活性研究引起人们极大的兴趣。据文献报道,将靛红酸酐,胺和醛加入到绿色环保试剂(如乙醇)体系中,以路易氏酸作催化剂,可以通过三组分一锅法得到含喹诺唑啉环的化合物,此类化合物具有一定的抗肿瘤活性。噻吩并嘧啶类化合物与喹诺唑啉具有类似结构的化合物。可以看成与喹诺唑啉的生物电子等排体。本论文以靛红酸酐的类似物,即2H-噻吩并[2,3-d] [1,3]恶嗪-2,4-(1H) - 二酮为原料,通过三组份一锅法合成噻吩并[2,3-d]嘧啶酮化合物。并对此反应进行了实验条件优化,即:以乙醇为溶剂,KOH为催化剂的条件下产率最佳。在此反应条件下可以有效、简便和快速地合成目标化合物,此反应条件温和、产率高、绿色环保且实用性强等特性。应用这一方法,合成了58个噻吩并[2,3-d]嘧啶酮类衍生物。所合成的化合物的结构都经过红外、氢谱、碳谱、质谱表征。化合物LF55还通过二维谱确定了每个信号的归属。另外,化合物LF10和LF21 经X衍射进一步确证了结构。对所有化合物进行抗肿瘤活性和部分抗流感活性筛选,活性结果表明:部分化合物具有抗肿瘤活性和抗流感活性与阳性对照药品阿霉素的IC50为2.61±0.29 μg/mL比较,化合物LF44对肿瘤(MCF-7)细胞有较好的抑制作用,其IC50值为14.44±3.50 μM,。化合物LF12和LF30表现出一定的抗流感活性,其IC50值分别为1.93 μg/mL和4.28 μg/mL,与阳性对照药品磷酸奥司他韦和利巴韦林值相当。有望继续开发,成为一类全新结构的抗流感药物。

Other Abstract

Thieno[2,3-d]pyrimidine derivatives are of great interest to synthetic chemists because of their diversed bioactivities. Recently, researchers reported the preparation of quinazoline ring compounds via multi-component reactions of isatoic anhydride, amino, and aldehyde in the presence of catalytic Lewis acids, in environmental friendly reagent ethanol. As the bioisosteres of quinazoline, thieno [2, 3-d] pyrimidin compounds display various bioactivities, such as anti-cancer and anti-inflammatory. In the present study, we used one-pot, three-component reaction and two step reaction to synthesis the thieno[2,3-d]pyrimidin type compounds from isatoic anhydride analouges, i.e. 2H-thieno[2,3-d][1,3]oxazine-2,4(1H)-diones. After optimatization, the best reaction condition was found in the presence of catalyst of KOH using ethanol as the solvent. This method provides rapid and efficient synthetic strategy for a library of products, at the same time have special advantages such as no special catalyst needed, high and diverse yield under relatively mild and practical reaction condition. The analytic spectrum of those compounds was documented. Their structures have been confirmed by IR, 1H NMR, 13C NMR, MS and LF55 has been confirmed by two-dimensional spectrum. LF10 and LF21 are also confirmed by X-ray crystal diffraction. Forthermore, biological activities against influenza activity and anti-tumor activity for these compounds are explored.Anti-tumor activity for some compounds: the compound LF44 show good antitumor activities, IC50 is 14.44±3.50 μM; The compounds LF12 and LF30 show better anti-influenza activities, IC50 are 1.93 μg/ml and 4.28 μg/ml;

Pages114
Document Type学位论文
Identifierhttp://ir.xjipc.cas.cn/handle/365002/5448
Collection资源化学研究室
Recommended Citation
GB/T 7714
刘飞泽. 噻吩并[2,3-d]嘧啶-4(3H)-酮衍生物的合成及其活性研究[D]. 北京. 中国科学院大学,2018.
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