a 辽宁师范大学化学化工学院 大连 116029) ( b 大连理工大学精细化工国家重点实验室 大连 116012) ( c 中国科学院上海药物研究所国家新药筛选中心 药物研究国家重点实验室 上海 201203) 摘要 大量研究表明, 细胞分裂周期 25 磷酸酯酶 B (Cdc25B)在许多癌症中都是过度表达的, 如乳腺癌、结肠癌、子宫 颈癌、肺癌等. 因此, 抑制 Cdc25B 是治疗癌症的一种潜在方法. 采用微波辐射法, 合成出了 20 个新的 2,6-二芳基-咪 唑[2,1-b][1,3,4]噻二唑衍生物 4, 然后再经 Vilsmeier-Haack 反应, 合成出了 19 个新的 2,6-二芳基-咪唑[2,1-b][1,3,4]噻二 唑-5-甲醛(5). 利用 IR, 1 H NMR 和元素分析对新的中间体化合物 3 及目标产物 4 和 5 进行了结构表征. 对所合成的目标 化合物 4 和 5 进行了 Cdc25B 抑制活性筛选. 实验结果表明, 在浓度为 5 μg/mL 时, 目标化合物 4c 对 Cdc25B 的抑制活 性最高, 抑制率为 87.68%, 目标化合物

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... 和 5m 具有中等的抑制活性, 其抑制率分别为 55.76%和 57.69%. 它们是潜在 的 Cdc25B 抑制剂. Abstract Researches indicate that the cell division cycle 25 phosphatase B (Cdc25B) is over-expressed in various primary human cancers including breast, colon, cervix, lung, etc. This suggests that the inhibition of Cdc25B may become a promising strategy in oncology. In this work, twenty novel 2,6-diaryl-imidazo[2,1-b][1,3,4]thiadiazoles 4 have been synthesized by microwave-assisted method. Then nineteen novel 2,6-diaryl-imidazo[2,1-b][1,3,4]thiadiazole-5-carbaldehydes (5) have obtained by Vilsmeier-Haack reaction. The structures of new compounds 3, 4 and 5 were characterized by IR, 1 H NMR spectra and elemental analysis. The synthesized target compounds 4 and 5 were screened for Cdc25B inhibitory activities. The results revealed that compound 4c showed the highest inhibitory activity against Cdc25B with percentage inhibition 87.68% at 5 μg/mL, compounds 4o and 5c showed moderate activities with percentage inhibition 55.76% and 57.69%, respectively. They can be considered as potential candidates as novel Cdc25B inhibitors.