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有机化学
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有机化学 ›› 2008, Vol. 28 ›› Issue (07): 1204-1206. 上一篇    下一篇

研究论文

新型含异噁唑环的喹唑啉衍生物的合成和抑蛋白酪氨酸酶 α和ε活性研究

雍建平a,b ; 阿吉艾克拜尔•艾萨*,a   

  1. (a中国科学院新疆理化技术研究所 乌鲁木齐 830011)
    (b中国科学院研究生院 北京 100039)
  • 收稿日期:2007-08-13 修回日期:2007-12-08 发布日期:2008-07-28
  • 通讯作者: 阿吉艾克拜尔•艾萨

Synthesis of Novel Isoxazole Ring Containing Quinazoline Deriva-tives and in vitro Inhibitory Activity Against PTPα and PTPε

YONG, Jian-Ping a,b; HAJI, Akber Aisa*,a   

  1. (a Xinjiang Technical Institute of Physics and Chemistry , Chinese Academy of Science, Urumqi 830011)
    (b Graduate School of Chinese Academy of Science, Beijing 100039)
  • Received:2007-08-13 Revised:2007-12-08 Published:2008-07-28
  • Contact: HAJI, Akber Aisa

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以2-氨基-4-硝基-苯甲酸和醋酸甲脒为原料, 合成了7-硝基-喹唑啉酮(3), 化合物3在SOCl2的作用下氯代得7-硝基-4-氯-喹唑啉(4); 又以取代苯甲醛为起始原料, 通过合成肟、1,3偶极环加成反应、甲磺酰化、叠氮化、Zn/NH4Cl 还原得中间体3-(取代苯基)-异噁唑-5-甲胺衍生物5a～5e. 4与5a～5e在碱性氧化铝作用下固相研磨合成了5种未见文献报道的新型的含异噁唑环的喹唑啉衍生物6a～6e. 所合成的化合物通过IR , 1H NMR, MS等分析方法进行了表征. 体外抑蛋白酪氨酸酶α (PTPα)和蛋白酪氨酸酶ε (PTPε)活性测试结果表明测试样品浓度在20 μg/mL下对PTPα和PTPε均无显著的抑制活性.

关键词: 7-硝基-4-氯-喹唑啉, 3-(取代苯基)-异噁唑-5-甲胺, 抗蛋白酪氨酸酶活性, 4-[3-(取代苯基)-异噁唑-5-甲氨基]-喹唑啉衍生物

7-Nitro-4-chrolo-quinazoline (4) was synthesized by two-step reactions using 4-nitro-2-amino-
benezic acid and formamidine acetate as starting materials. And then, 3-(substituted-phenyl)-
isoxazole-5-methylamine derivatives 5a～5e were synthesized by synthesizing substituted benaldehyde oxime, [3＋2] dipolar cycloaddition reaction with propargyl alcohol, then acylation with methanesulfonyl chloride, substitution with NaN3 and reduction with Zn/NH4Cl. Subsequently, 3-(substituted-phenyl)isoxa- zole-5-methylamino-4(3H)-quinazoline derivatives 6a～6e were obtained by solid-grinding 5a～5e and 4 under the basic Al2O3 at room temperature. Their structures were confirmed by IR, HNMR and ESI-MS spectra. The compounds 6a, 6c and 6d were assayed in vitro activity against PTPα, PTPε, and showed that the tested compounds had no notable inhibitory activity in the concentration of 20 μg/mL.

Key words: 3-(substituted-phenyl)-isoxazole-5-methylamine, PTPε, 3-(substituted- phenyl)-isoxazole-5-methylamino-4(3H)-quinazoline derivative, inhibitory activity against PTPα, 7-nitro-4-chrolo-quinazoline