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有机化学 ›› 2010, Vol. 30 ›› Issue (04): 582-589. 上一篇    下一篇

研究论文

含有异噁唑环的β-氨基酮的合成及其抗糖尿病活性的初步研究

周祖文1，晏菊芳2，唐雪梅1，张蔚瑜2，张映霞1，陈欣2，苏小燕1，杨大成*,1   

  1. (1西南大学化学化工学院 重庆 400715)
    (2成都地奥制药集团药物筛选中心 成都 610041)
  • 收稿日期:2009-08-24 修回日期:2009-11-25 发布日期:2010-04-28
  • 通讯作者: 杨大成 E-mail:hxydc@swu.edu.cn

Synthesis and Preliminary Evaluation of Antidiabetic Activity for β-Amino Ketone Containing Isoxazole Moiety

Zhou Zuwen1 Yan Jufang2 Tang Xuemei1 Zhang Weiyu2 Zhang Yingxia1 Chen Xin2 Su Xiaoyan1 Yang Dacheng*,1   

  1. (1 School of Chemistry and Chemical Engineering, Southwest University, Chongqing 400715)
    (2 Chengdu Di Ao Pharmaceutical Group, Chengdu 610041)
  • Received:2009-08-24 Revised:2009-11-25 Published:2010-04-28

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为了寻找新型高效低毒的抗糖尿病分子, 由Mannich反应一步合成了15个新的含有异噁唑结构单元的β-氨基酮, 制备方法简便、反应条件温和、产品易纯化, 收率为51.2%～89.3%. 所得化合物结构均通过1H NMR, 13C NMR, ESI MS和HR MS表征. 生物活性实验结果表明, 在低浓度范围, 目标分子对蛋白质酪氨酸磷酸酶1B和α-葡萄糖苷酶抑制活性不高, 但对过氧化物酶体增殖物激活受体的激动活性强度中等, 其中化合物1-(3,4-二氯苯基)-3-(5-甲基异噁唑-3-氨基)-3-(6-甲氧基萘-2-基)-1-丙酮(15)的PPAR激动活性最好, 达到75.3%, 值得进一步研究. 还讨论了目标分子的合成条件及其结构-活性关系.

关键词: 糖尿病, 异噁唑, β-氨基酮, Mannich反应

In order to find highly active antidiabetic compounds, fifteen new β-amino ketones containing a isoxazole moiety were synthesized directly through Mannich reaction with facile method and mild reaction condition in the yields of 51.2%～89.3%. Their structures were confirmed by 1H NMR, 13C NMR, ESI MS and HR MS techniques. Preliminary bioassay indicated that although most of these compounds possess weak α-glucosidase inhibitory activity and protein tyrosine phosphatase 1B inhibitory activity in low concentration, some could activate peroxisome proliferator-activated receptors (PPAR) response element moderately. Compound 1-(3,4-dichlorophenyl)-3-(6-methoxynaphthalen-2-yl)-3-(5-methylisoxazol-3-ylamino)propan- 1-one (15) has the strongest activity (75.3%), which deserved further study. The reaction conditions and the structure-activity relationship of these compounds were also discussed in this paper．

Key words: diabetes mellitus, isoxazole, β-amino ketone, Mannich reaction