1,3,4-(口恶)二唑硫醚酰胺为核心骨架的新型多杂环分子的合成及对Cdc25B与PTP1B的抑制活性

首先利用含有三嗪的芳香酰肼(3)构筑了1,3,4-噁二唑衍生物(5), 然后将化合物5与含有1,3,4-噻二唑的衍生物(6)拼合合成了18个目标分子. 利用红外光谱(IR)、 核磁共振波谱(NMR)和高分辨质谱(HRMS)等技术对其结构进行了表征. 考察了目标分子对细胞分裂周期25磷酸酯酶B(Cdc25B)和蛋白酪氨酸磷酸酯酶1B(PTP1B)的抑制活性. 结果表明, 有8个目标分子的抑制活性优于其阳性对照物, 有望成为潜在的Cdc25B抑制剂; 有12个目标分子的抑制活性优于其对照物, 有望成为潜在的PTP1B抑制剂.

Synthesis of Novel Polyheterocyclic Molecules with 1,3,4-Oxadiazole Thioetheramide as Core Framework and Their Inhibitory Activity on Cdc25B and PTP1B†

1,3,4-Oxadiazole derivatives(5) were constructed using aromatic hydrazide containing a triazines(3). Then, compound 5 was combined with the derivatives 6 containing 1,3,4-thiadiazole to synthesize eighteen target molecules. Their structures were characterized by infrared spectroscopy(IR), nuclear magnetic resonance(NMR) and high resolution mass spectrometry(HRMS). The inhibitory activities of the target molecules against cell division cycle 25B(Cdc25B) and protein tyrosine phosphatase 1B(PTP1B) were evaluated. The results showed that eight target molecules had better inhibitory activities than their positive reference and could be expected to be potential Cdc25B inhibitors; twelve target molecules had better inhibitory activities than their reference and could be expected to be potential PTP1B inhibitors.