N.D. Zelinsky Institute of Organic Chemistry, Russian Academy of Sciences, 47 Leninsky Prosp., Moscow, Russian Federation, 119991.
Institute of Physiologically Active Compounds of the Russian Academy of Sciences, 1 Severnyi Proezd, Chernogolovka, Russian Federation, 142432.
Mol Divers. 2018 Aug;22(3):585-599. doi: 10.1007/s11030-018-9813-8. Epub 2018 Mar 14.
A series of tetrahydroimidazo[4,5-e]thiazolo[3,2-b]-1,2,4-triazine-2,7(1H, 6H)-diones were synthesized via the reaction of imidazotriazinethiones and bromoacetic acid followed by condensation with isatins. Amidine skeletal rearrangement of 3,3a,9,9a-tetrahydroimidazo[4,5-e]thiazolo[3,2-b]-1,2,4-triazine-2,7 (1H, 6H)-diones into 1,3a,4,9a-tetrahydroimidazo[4,5-e]thiazolo[2,3-c]-1,2,4-triazine-2,8 (3H, 7H)-diones under KOH treatment has been studied. The influence of substituents at positions 1,3,3a,6,9a of imidazothiazolotriazine on the ability to undergo rearrangement was analyzed based on experimental data and theoretical calculations. Both imidazothiazolo[3,2-b]triazines and their rearrangement products were evaluated for their cytotoxic activity against rhabdomyosarcoma, A549, HCT116 and MCF7 human cancer cell lines by MTT assay. Among the derivatives, 1,3-diethyl-6-[1-(2-propyl)-2-oxoindolin-3-ylidene]-3,3a,9,9a-tetrahydroimidazo [4,5-e]thiazolo[3,2-b]-1,2,4-triazine-2,7(1H, 6H)-dione 4i was found to have the highest antiproliferative activity toward the tested cell lines (4i: [Formula: see text], 2.29, 0.47 and [Formula: see text], respectively). The [Formula: see text] value of compound 4i against normal human embryonic kidney cells HEK293 was [Formula: see text], which appeared to be 6-41-fold higher than [Formula: see text] values of 4i against human cancer cells.
一系列四氢咪唑并[4,5-e]噻唑并[3,2-b]-1,2,4-三嗪-2,7(1H,6H)-二酮是通过咪唑并三嗪硫酮与溴乙酸反应，然后与靛红缩合合成的。用 KOH 处理研究了 3,3a,9,9a-四氢咪唑并[4,5-e]噻唑并[3,2-b]-1,2,4-三嗪-2,7(1H,6H)-二酮的酰胺骨架重排为 1,3a,4,9a-四氢咪唑并[4,5-e]噻唑并[2,3-c]-1,2,4-三嗪-2,8(3H,7H)-二酮。根据实验数据和理论计算分析了咪唑并噻唑并三嗪中 1、3、3a、6、9a 位取代基对重排能力的影响。通过 MTT 法评估了咪唑并[3,2-b]三嗪及其重排产物对横纹肌肉瘤、A549、HCT116 和 MCF7 人癌细胞系的细胞毒性活性。在衍生物中，1,3-二乙基-6-[1-(2-丙基)-2-氧代吲哚啉-3-亚基]-3,3a,9,9a-四氢咪唑并[4,5-e]噻唑并[3,2-b]-1,2,4-三嗪-2,7(1H,6H)-二酮 4i 对测试的细胞系表现出最高的增殖抑制活性（4i：[化学式：见文本]，2.29，0.47 和 [化学式：见文本]，分别）。化合物 4i 对正常人类胚胎肾细胞 HEK293 的[化学式：见文本]值为[化学式：见文本]，这似乎比 4i 对人类癌细胞的[化学式：见文本]值高 6-41 倍。
