1,4-双[3-脂肪基/苯基-1,2,4-三唑并[3,4-b]-1,3,4-噻二唑-6-基]芳基衍生物的合成与生物活性

在三氯氧磷催化下, 6种3-脂肪基-1,2,4-三唑(1a~1f)和3-苯基-1,2,4-三唑(1g)分别与对苯二甲酸和2-氨基-1,4-对苯二甲酸发生环化反应, 高产率合成了14种双枝三唑并噻二唑稠环衍生物(2和3), 并对其进行了结构表征及药物活性测试. 目标化合物对Cdc25B和PTP1B抑制活性筛选结果表明, 化合物2f, 3a和3g对Cdc25B有较高的抑制活性, IC₅₀值分别为(3.45±0.60), (0.69±0.10)和(1.52±0.19) μg/mL; 化合物3a和3b对PTP1B表现出较高的抑制活性, IC₅₀值分别为(0.98±0.13)和(2.00±0.16) μg/mL.

Synthesis and Bioactivity of 1,4-Bis[3-aliphatic/aryl -1,2,4-triazole[3,4-b]-1,3,4-thiatriazole-6-yl] Aryl Derivatives†

Fourteen new bis-1,2,4-triazole[3,4-b]-[1,3,4]thiadiazol-6-yl derivatives(2 and 3) were synthesized in high yields through the reactions of six 3-aliphatic-1,2,4-triazole derivatives(1a—1f) and 3-phe-nyl-1,2,4-triazole(1g) with terephthalic acid and 2-aminoterephthalic acid, respectively, in the presence of phosphorus oxychloride. The structures of target compounds were characterized and the inhibitory properties of Cdc25B and PTP1B were studied. The results showed that compounds 2f, 3a and 3g exhibited high inhibitory activity against Cdc25B enzyme with IC₅₀ values of (3.45±0.60), (0.69±0.10) and (1.52±0.19) μg/mL, respectively. Compounds 3a and 3b showed high inhibitory activity against PTP1B with IC₅₀ values of (0.98±0.13) and (2.00±0.16) μg/mL.