新型3,6-二取代三唑并噻二唑衍生物的合成及细胞分裂周期25B磷酸酶和蛋白酪氨酸磷酸酶1B抑制活性研究
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摘要
以邻苯二胺和一氯乙酸为初始原料,经多步反应,合成了一系列新型含苯并咪唑环和芳磺酰基的3,6-二取代三唑并噻二唑衍生物7a~7y.利用~1H NMR、IR和元素分析对新的中间体化合物3、4、6及目标产物7进行了结构表征.对所合成的目标化合物进行了细胞分裂周期25B磷酸酶(Cdc25B)和蛋白酪氨酸磷酸酶1B(PTP1B)抑制活性筛选,实验结果显示,部分目标化合物对Cdc25B和PTP1B显示出良好的抑制活性,其中目标化合物7d对Cdc25B的抑制活性最高[IC50=(7.72±0.73)mg/m L],7u对PTP1B的抑制活性最高[IC50=(3.31±0.57)mg/m L].值得注意的是,化合物7b、7d、7l、7t和7u对Cdc25B和PTP1B均具有抑制活性.这些活性的目标化合物是潜在的Cdc25B和PTP1B抑制剂,在癌症和糖尿病治疗方面具有很好的应用前景.
A series of new 3,6-disubstituted triazolothiadiazole derivatives 7a~7y containing benzimidazole and arylsulfonyl moities have been synthesized by o-phenylenediamine and chloroacetic acid as starting materials via multistep reactions. The structures of the intermediates 3, 4, 6 and the target compounds 7 were characterized by ~1H NMR, IR spectra and elemental analysis. All synthesized target compounds were screened for their inhibitory activity against cell division cycle 25 B phosphatase(Cdc25B) and protein tyrosine phosphatase 1B(PTP1B). The results show that some of them display significant inhibitory activities against Cdc25 B and PTP1 B. Among them, compound 7d exhibits the highest inhibitory activity against Cdc25 B [IC_(50)=(7.72±0.73) μg/m L] and 7u exhibits the highest inhibitory activity against PTP1 B [IC_(50)=(3.31±0.57) μg/m L]. It is noteworthy that compounds 7b, 7d, 7l, 7t and 7u show higher inhibitory activities against Cdc25 B and PTP1 B. They can be considered as potential Cdc25 B and PTP1 B inhibitors, and have great application prospects in the treatment of cancers and diabetes.
A series of new 3,6-disubstituted triazolothiadiazole derivatives 7a~7y containing benzimidazole and arylsulfonyl moities have been synthesized by o-phenylenediamine and chloroacetic acid as starting materials via multistep reactions. The structures of the intermediates 3, 4, 6 and the target compounds 7 were characterized by ~1H NMR, IR spectra and elemental analysis. All synthesized target compounds were screened for their inhibitory activity against cell division cycle 25 B phosphatase(Cdc25B) and protein tyrosine phosphatase 1B(PTP1B). The results show that some of them display significant inhibitory activities against Cdc25 B and PTP1 B. Among them, compound 7d exhibits the highest inhibitory activity against Cdc25 B [IC_(50)=(7.72±0.73) μg/m L] and 7u exhibits the highest inhibitory activity against PTP1 B [IC_(50)=(3.31±0.57) μg/m L]. It is noteworthy that compounds 7b, 7d, 7l, 7t and 7u show higher inhibitory activities against Cdc25 B and PTP1 B. They can be considered as potential Cdc25 B and PTP1 B inhibitors, and have great application prospects in the treatment of cancers and diabetes.
引文
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