Based on the observed biological activity of 1,2,4-triazin-5-one derivatives and their cyclic analogues, a novel series of 7-thiazolo[3,2-]-1,2,4-triazin-7-one derivatives that contain ester moiety compounds carboxylic acid moiety compounds and piperazine amide moiety compounds at position-3 of the thiazolotriazinone scaffold were synthesized. The intermolecular cyclization occurred regioselectively at N2-position of 1,2,4-triazine ring was characterized by X-ray single-crystal diffraction analysis. The biological activities of the target compounds were assayed against some bacterial strains. Compared with ciprofloxacin, compounds and exhibited more excellent antibacterial activity, especially the activity against , showing that the fluorine at the para position of the benzyl group would be the best choice. In addition, compounds with carboxylic acid moiety can enhance the antibacterial activity. Compounds containing bulky 1-(substituted phenyl)piperazine moiety were found with slightly less biological activity. Similar to ciprofloxacin, the docking result of target compounds with DNA topoisomerase II indicates the carboxyl group of the target compounds with carboxylic acid moiety has a crucial salt bridge interaction with Mg in the protein.

中文翻译：

---

新型7H-噻唑并[3,2-b]-1,2,4-三嗪-7-酮衍生物的设计、合成及其抗菌活性


基于观察到的 1,2,4-三嗪-5-酮衍生物及其环状类似物的生物活性，一系列新型 7-噻唑并[3,2-]-1,2,4-三嗪-7-酮衍生物合成了在噻唑并三嗪酮骨架的3位上含有酯部分化合物、羧酸部分化合物和哌嗪酰胺部分化合物的化合物。通过X射线单晶衍射分析表征了1,2,4-三嗪环N2位区域选择性发生的分子间环化。针对某些细菌菌株测定了目标化合物的生物活性。与环丙沙星相比，化合物 和 表现出更优异的抗菌活性，特别是对 的活性，表明苄基对位的氟是最佳选择。此外，带有羧酸部分的化合物可以增强抗菌活性。含有大量 1-(取代苯基)哌嗪部分的化合物被发现具有稍低的生物活性。与环丙沙星类似，目标化合物与DNA拓扑异构酶II的对接结果表明，目标化合物的羧酸部分的羧基与蛋白质中的Mg存在关键的盐桥相互作用。