含吡啶组块3-脂肪基-1,2,4-三唑并[3,4-b]-1,3,4噻二唑衍生物的合成及生物活性

Synthesis and Biological Activities of 3-Aliphatic-1,2,4-Triazole[3,4-b]-1,3,4-Thiatriazole Derivatives Containing Pyridine Unit

分别将6种脂肪酸与二氨基硫脲反应,合成了6种含不同碳数的3-脂肪基-1,2,4-三唑(1a^1f),其中化合物1e和1f为首次合成。在三氯氧磷存在下,分别将化合物1a^1f与4-吡啶甲酸和2,6-吡啶二甲酸反应,首次高产率合成了12种三唑并噻二唑衍生物(2a^2f)和(3a^3f)。为对比引入3-脂肪基和吡啶组块对生物活性的影响,分别合成了3-苯基含吡啶组块产物(5)、双枝3-苯基含吡啶组块化合物(6)、不含吡啶组块的化合物(7a^7c)和(8a^8c)。应用IR、1H NMR和HRMS等技术手段对19种新物质进行了结构表征,并研究了其对Cdc25B和PTP1B的抑制性能,研究结果表明,含有吡啶组块的双枝脂肪基化合物3b、3d、3e和3f对Cdc25B有良好的抑制活性,IC50值(mg/L)分别为1.12±0.27、2.72±1.07、0.72±0.05和4.97±0.93;化合物2b、3d和5对PTP1B表现出较高的抑制活性,IC50值(mg/L)分别为0.98±0.13、1.33±0.11和2.18±0.20。

3-Aliphatie-1,2,4-triazole derivatives la - If were synthesized through the reaction of six kinds of fatty acids with diaminothiourea, in which compounds le and If were first synthesized. In the presence of phosphorus oxychloride, compounds la- If reacted with 4-pyridine earboxylie acid and 2, 6-pyridine diearboxylie acid, respectively. The 12 kinds of aliphatic triazoles, thiadiazoles 2a ~ 2f and 3a -3f were synthesized in high yields for the first time. In order to study the influence of 3-aliphatic group and pyridine, compounds 5, 6, 7a ~ 7c and 8a -8c without pyridine units were also synthesized. The target compounds were well characterized by IR, 1H NMR and HRMS. In the biotic screening test, the inhibitory properties of Cde25B and PTP1B were explored. The results show that compounds 3b, 3d, 3e and 3f have good inhibition activity against Cdc25B with IC50 values of （1.12 ± 0.27 ）, （2.72 ± 1.07）, （0. 72 ± 0. 05 ） and （4.97 ± 0. 93） mg/L, respectively; compounds 2b, 3d, and 5 exhibit higher inhibition activity against PTP1B with IC50 values of （0. 98 ±0. 13）, （1.33 ±0. 11）, （2. 18 ±0.20） mg/L, respectively.