化学学报 ›› 2006, Vol. 64 ›› Issue (15): 1559-1564. 上一篇    下一篇

研究论文

萘普生噻唑衍生物的设计和合成及其环氧合酶-2抑制活性的体外评价

郭长彬, 郭彦伸, 郭宗儒*, 肖景发, 褚凤鸣, 程桂芳   

  1. (中国医学科学院中国协和医科大学药物研究所 北京 100050)
  • 收稿日期:2005-10-24 修回日期:2006-01-06 出版日期:2006-08-14 发布日期:2006-08-14
  • 通讯作者: 郭宗儒

Design, Synthesis and in vitro Evaluation of Thiazole Derivatives of Naproxen as Cyclooxygenase-2 Inhibitors

GUO Chang-Bin, GUO Yan-Shen, GUO Zong-Ru*, XIAO Jing-Fa
CHU Feng-Ming, CHENG Gui-Fang   

  1. (Institute of Materia Medica, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050)
  • Received:2005-10-24 Revised:2006-01-06 Online:2006-08-14 Published:2006-08-14
  • Contact: GUO Zong-Ru

基于环氧合酶-2 (COX-2)与COX-1结构上的差异, 设计了萘普生的噻唑衍生物, 以期利用COX-2的侧面口袋, 增加对COX-2的结合作用. 以萘普生为原料经四步反应合成7个目标化合物, 其结构经核磁共振氢谱、质谱和元素分析(或高分辨质谱)确证. 体外筛选结果表明, 化合物有一定的COX-2抑制活性.

关键词: 萘普生, 环氧合酶-2, 抑制剂, 噻唑衍生物

Based on the differences between cyclooxygenase-2 (COX-2) and COX-1, a series of derivatives of naproxen in which the carboxyl group was replaced with a variety of substituted thiazolyls were designed. Seven target compounds were synthesized in four steps with naproxen as a starting material and structurally confirmed by 1H NMR, MS and elemental analysis or HRMS. The biological tests showed that some of them have inhibitory activity against COX-2 in vitro.

Key words: naproxen, cyclooxygenase-2, inhibitor, thiazole derivative