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

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.

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

Fifteen novel 2-methyl-3-(1’,2’-O-cyclohexylidendioxyethyl)-5-aryl-3a,6a-dihydro-4,6-dioxopyrrolino3’,4’-d]-structures of the target compounds 4a～4o were characterized by 1H NMR,IR spectra and elemental analysis.The preliminaryisoxazolinium-tetrachloroferrate derivatives 4a～4o were synthesized by N-methylation of the corresponding isoxazoline us-ing dimethyl sulfate as a methylating reagent and ferric(III)-chloride as anion exchange reagent in hydrochloric acid.The 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.