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GFDA2唑并[5,4-d]嘧啶类化合物的设计、合成及其抗肿瘤活性
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引用本文:李明涛,徐丹,薛文君,尤启冬,孙丽萍.GFDA2唑并[5,4-d]嘧啶类化合物的设计、合成及其抗肿瘤活性[J].中国药科大学学报(中文版),2017,48(4):425-431
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李明涛# 中国药科大学药学院药物化学教研室江苏省药物分子设计与成药性优化重点实验室 
徐丹# 中国药科大学药学院药物化学教研室江苏省药物分子设计与成药性优化重点实验室 
薛文君 中国药科大学药学院药物化学教研室江苏省药物分子设计与成药性优化重点实验室 
尤启冬 中国药科大学药学院药物化学教研室江苏省药物分子设计与成药性优化重点实验室 
孙丽萍 中国药科大学药学院药物化学教研室江苏省药物分子设计与成药性优化重点实验室 
基金项目:国家自然科学基金资助项目(No.20872181,No.21172265)#李明涛和徐丹对本论文的贡献相同
中文摘要:为了寻找具有更好抗肿瘤活性的化合物,设计合成了一系列GFDA2唑并[5,4-d]嘧啶类衍生物。以盐酸乙脒为起始原料,合成了13个化合物8a~8m;目标化合物结构经IR、1H NMR、EI-MS和元素分析确证;采用MTT法先后对目标化合物进行了人脐静脉内皮细胞(HUVEC)的抗肿瘤血管生成抑制活性测试和3株肿瘤细胞(A549、HepG2、U251)的体外抗肿瘤活性测试;结果表明,化合物8c8d8g8i和8l对HUVEC和3株不同肿瘤细胞表现出明显的增殖抑制活性;化合物8l对A549、HepG2和U251的抑制活性略优于阳性对照药舒尼替尼,值得进一步研究。
中文关键词:GFDA2唑并[5,4-d]嘧啶类衍生物  合成  抗血管生成  抗肿瘤活性
 
Design, synthesis and antitumor activities of oxazolo[5, 4-d]pyrimidine derivatives
Abstract:A series of oxazole[5, 4-d]pyrimidine derivatives were designed and synthesized to discover novel compounds with antitumor activity. Compounds 8a-8m were synthesized using acetamidine hydrochloride as the start material. The structures of synthesized compounds were confirmed by IR, 1H NMR, EI-MS and elemental analysis. The antiangiogenesis activities of the synthesized compounds were determined by MTT in human umbilical vein endothelial cell(HUVEC). The in vitro antitumor activities of the synthesized compounds were determined by MTT assay in A549, HepG2 and U251. Compounds 8c, 8d, 8g, 8i and 8l were found to inhibit the proliferation of all the tested cell lines. Compound 8l exhibited noteworthy activities in A549, HepG2 and U251 cell lines with IC50value lower than the positive reference sunitinib, suggesting that compound 8l might be the promising antitumor agent for further investigation.
keywords:oxazole[5,4-d]pyrimidine derivatives  synthesis  anti-angiogenesis  antitumor activity
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