中华医学超声杂志

应用化学 ›› 2010, Vol. 27 ›› Issue (09): 1026-1031.DOI: 10.3724/SP.J.1095.2010.90506

• 研究论文 • 上一篇    下一篇

4-(3-(4-羟基苯基) -3-氧代-1-芳基丙氨基)-N-(5-甲基异噁唑-3-基)苯磺酰胺的合成与抗糖尿病活性

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

  1. (1.西南大学化学化工学院 重庆 400715;2.成都地奥制药集团有限公司药物筛选中心 成都)
  • 收稿日期:2009-07-27 修回日期:2010-03-11 出版日期:2010-09-10 发布日期:2010-09-10
  • 通讯作者: 杨大成, 男, 博士, 教授; E-mail:hxydc@swu.edu.cn; 研究方向：有机反应及药物合成
  • 基金资助:
    重庆市自然科学基金(2005BB5095)西南师大博士科研基金(SWNU.B2005010)和高新技术培育基金(XSGX05)资助项目

Synthesis and Preliminary Evaluation of Antidiabetic Activity of 4-(3- (4-Hydroxyphenyl)-3-oxo-1-arylpropylamino)-N-(5-Methylisoxazol-3-yl) Benzenesulfonamide

ZHANG Ying-Xia1, YAN Ju-Fang2, FAN Li1, ZHANG Wei-Yu2, SU Xiao-Yan1, CHEN Xin2, TANG Xue-Mei1, ZHOU Zu-Wen1, YANG Da-Cheng1*   

  1. (1.School of Chemistry and Chemical Engineering,Southwest University,Chongqing 400715;
    2.Drug Screening Center,Chengdu Di Ao Pharmaceutical Group Co. Ltd,Chengdu)
  • Received:2009-07-27 Revised:2010-03-11 Published:2010-09-10 Online:2010-09-10

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摘要：

由磺胺甲噁唑、对羟基苯乙酮和芳香醛反应直接合成了13个未见报道的β-氨基酮，反应选择性发生在羰基α位。产物结构通过1H NMR、13C NMR、MS进行了表征。生物活性试验显示，低浓度范围，所得化合物不仅显示一定的蛋白质酪氨酸磷酸酶1B(PTP1B)和α-葡萄糖苷酶抑制活性，而且具有中等强度的过氧化物酶体增殖物激活受体反应元件(PPRE)的激动活性，8个化合物的激动活性超过40％，其中化合物11的活性达到72.7％。

关键词: α-葡萄糖苷酶, 蛋白质酪氨酸磷酸酶1B, 过氧化物酶体增殖物激活受体反应元件, 对羟基苯乙酮, 磺胺甲噁唑, β-氨基酮, Mannich反应

Abstract:

Thirteen new β-amino ketones were designed and synthesized directly through the Mannich reaction of sulfamethoxazole, 4-hydroxyacetophenone and aromatic aldehydes in good yields. The reaction selectively occurred at the α-position of the carbonyl group of 4-hydroxyacetophenone. Their chemical structures were confirmed by means of 1H NMR, 13C NMR and MS. Biological activity tests showed that in the rage of low concentrations, these title compounds displayed a certain inhibitory activity against protein tyrosine phosphatase 1B(PTP1B) and α-glucosidase. Moreover, some could activate the peroxisome proliferatoractivated receptor response element(PPRE) moderately. The PPRE agonist activity of eight compounds was over 40%, among them compound 11 showed the highest activity(72.7%), which deserved further study.

Key words: α-Glucosidase, PTP1B, PPRE, hydroxyacetophenone, sulfamethoxazole, β-amino ketone

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