论文部分内容阅读
硫酸二甲酯作为N-甲基化试剂,与相应的异噁唑啉反应,并在盐酸中三氯化铁作为阴离子交换试剂,合成了15个未见文献报道的2-甲基-3-(1’,2’-二-O-环亚己基二氧乙基)-5-芳基-3a,6a-二氢-4,6-二氧代氮杂茂并[3’,4’-d]异噁唑四氯化铁酸盐衍生物4a～4o.化合物4a～4o结构结构经1H NMR,IR和元素分析确证,并进行了初步药物活性筛选,大部分化合物显示了不同程度的抗癌和抗炎症性及免疫性疾病活性.体外抗癌活性试验表明,当样品浓度为20μg/mL时,除了4h无活性外,其余化合物对细胞分裂周期磷酸酯酶Cdc25B的抑制率为≥97.55%.此外,体外白细胞共同抗原活性试验表明,当样品浓度为20μg/mL时,所有化合物4a～4o对白细胞共同抗原CD45蛋白酪氨酸磷酸酶A具有良好的抑制活性,其抑制率为68.41%～93.38%.在此基础上,初步讨论了该类化合物的构效关系.
Dimethyl sulfate was used as an N-methylating reagent to react with the corresponding isoxazolines. In the presence of FeCl3 as an anion exchange reagent in hydrochloric acid, 15 unreplaced 2-methyl-3- (1 ’, 2’-di-O-cyclohexylidenedioxyethyl) -5-aryl-3a, 6a-dihydro-4,6-dioxoazepino [3’, 4’- d] isoxazole ferrochloride derivatives 4a ~ 4o. The structures of compounds 4a ~ 4o were confirmed by 1H NMR, IR and elemental analysis, and the preliminary drug activity screening was performed. Most of the compounds showed different degrees of resistance Cancer and anti-inflammatory and immune disease activity in vitro test showed that when the sample concentration of 20μg / mL, in addition to 4h no activity, other compounds on the cell cycle of the phosphatase Cdc25B inhibition rate of ≥ 97.55% In addition, in vitro leukocyte common antigen activity test showed that when the sample concentration of 20μg / mL, all compounds 4a ~ 4o on the leukocyte common antigen CD45 protein tyrosine phosphatase A has a good inhibitory activity, the inhibition rate was 68.41% 93.38% .Based on this, the structure-activity relationship of these compounds was discussed preliminarily.