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

Chin. J. Org. Chem. ›› 2010, Vol. 30 ›› Issue (04): 582-589. Previous Articles Next Articles

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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 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

Abstract

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

Cite this article

ZHOU Jie-Wen, YAN Ju-Fang, TANG Xue-Mei, ZHANG Wei-Yu, ZHANG Yang-Xia, CHEN Xin, SU Xiao-Yan, YANG Da-Cheng. Synthesis and Preliminary Evaluation of Antidiabetic Activity for β-Amino Ketone Containing Isoxazole Moiety[J]. Chin. J. Org. Chem., 2010, 30(04): 582-589.

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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

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

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