有机化学 ›› 2012, Vol. 32 ›› Issue (02): 376-381 .DOI: 10.6023/cjoc1104222 上一篇    下一篇

研究论文

新型二氧代氮杂茂并[3',4'-d]N-甲基异噁唑四氯化铁酸盐衍生物的合成及其生物活性

图尔麦麦提·艾力, 穆赫塔尔·伊米尔艾山, 阿依努尔·胡达依别尔根   

  1. 新疆大学化学与化工学院 乌鲁木齐 830046
  • 收稿日期:2011-04-22 修回日期:2011-09-14 发布日期:2012-03-09
  • 通讯作者: 穆赫塔尔·伊米尔艾山 E-mail:imerhasan@xju.edu.cn
  • 基金资助:

    国家自然科学基金(No. 21062019)资助项目.

Synthesis and Bioactivity of Novel Dioxy-pyrrolino[3',4'-d]-N-methylisoxazolinium-tetrachloroferrate Derivatives

Turmuhammad Ali, Mukhtar Imerhasan, Aynur Hudabergen   

  1. College of Chemistry and Chemical Engineering, Xinjiang University, Urumqi 830046
  • Received:2011-04-22 Revised:2011-09-14 Published:2012-03-09
  • Supported by:

    Project supported by the National Natural Science Foundation of China (No. 21062019).

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20 μg/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20 μg/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.

关键词: N-甲基异噁唑四氯化铁酸盐, 合成, 生物活性

Fifteen novel 2-methyl-3-(1',2'-O-cyclohexylidendioxyethyl)-5-aryl-3a,6a-dihydro-4,6-dioxopyrrolino[3',4'-d]- isoxazolinium-tetrachloroferrate derivatives 4a~4o were synthesized by N-methylation of the corresponding isoxazoline using dimethyl sulfate as a methylating reagent and ferric(III)-chloride as anion exchange reagent in hydrochloric acid. The structures of the target compounds 4a~4o were characterized by 1H NMR, IR spectra and elemental analysis. The preliminary in vitro bioassay on the compounds showed that most compounds possess anti-cancer activity and the Leukocyte common antigen activity at some extent. At the test concentration of 20 μg/mL, all compounds showed inhibition activity of ≥97.55% against Cdc25B (cell division cycle 25B) phosphatase except for compound 4h, and inhibition activity of 68.41%~93.38% against leukocyte common antigen (LCK) CD45 protein tyrosine phosphatase A, respectively. Preliminary discussion was carried out on the structure-activity relationship of the target compounds.

Key words: N-methylisoxazolinium-tetrachloroferrate, synthesis, bioactivity