V型对称三唑并噻二唑衍生物的合成与生物活性  

Syntheses and Biological Activities of V-Shaped Symmetrical Triazolothiazine Oxadiazole Derivatives

作　　者：张成路[1] 王雪[1] 胡雪[1] 孙丽杰[1] 曲瑞峰[1] 国阳[1] 柴金华[1] 朱长安[1] 

机构地区：[1]辽宁师范大学化学化工学院,辽宁省生物与制药重点实验室,大连116029

出　　处：《高等学校化学学报》2015年第3期463-468,共6页Chemical Journal of Chinese Universities

基　　金：辽宁省教育厅科学技术资助项目(批准号:2009A426)资助~~

摘　　要：为构筑V型对称结构的三唑并噻二唑类衍生物,将间苯二甲酸和5-氨基间苯二甲酸分别与3-脂肪基-1,2,4-三唑(1)缩合,在POCl3催化下,合成了14个V型对称结构三唑并噻二唑稠环衍生物(2a^2g和3a^3g),其中13个化合物为首次合成.通过红外光谱、核磁共振波谱和高分辨质谱等对目标产物的结构进行了表征.研究了目标产物对细胞周期分裂蛋白25B(Cdc25B)和蛋白酪氨酸磷酸酶1B(PTP1B)的抑制性能,结果发现,部分目标产物对Cdc25B表现出良好的抑制活性,其中化合物3b和3f的抑制活性IC50值分别为(1.34±0.39)和(0.61±0.09)μg/m L,有望作为治疗癌症的潜在Cdc25B抑制剂;化合物3b^3g对PTP1B均表现出良好的抑制活性,其中化合物3b和3e的IC50值分别为(0.36±0.05)和(0.97±0.08)μg/m L,有望作为治糖尿病的潜在PTP1B抑制剂.To build V-shaped symmetrical structure thiadiazole derivatives, isophthalic acid and 5-amin- oisophthalic acid condensed with 3-aliphatie-1,2,4-triazole （1） respectively. In POCI3 presence, fourteen symmetrical V-shaped triazolo-thiadiazole derivatives（2a-2g and 3a-3g） were synthesized, wherein thirteen of them were first synthesized, and the structures of compounds 2 and 3 were characterized by infrared （IR） , nuclear magnetic resonance（NMR） and high resolution mass spectrometer（HRMS）. The inhibitory activities of the target compounds were screened for Cdc25B and PTP1B. The results showed that some eompouds exhibited inhibitory activities against Cde25B, compounds 3b and 3f may be used as potential Cdc25B inhibitors in the treatment of cancer. Compouds 3b-3g exhibited inhibitory activities against vrP1B. Compounds 3b and 3e may be used as potential PTP1B inhibitors in the treatment of diabetes.

关 键 词：3-脂肪基-1 2 4-三唑 药物活性筛选 CDC25B PTP1B 

分 类 号：O626.23[理学—有机化学]