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有机化学 ›› 2007, Vol. 27 ›› Issue (06): 733-738. 上一篇    下一篇

研究论文

3-(羟基-p-甲磺酰苯甲撑基)-5-氯-2-吲哚酮-1-羧酰胺类化合物的合成及生物活性研究

赖宜生*,a，张奕华a，李月珍b，季晖c，杨茗c，丛日刚a   

  1. (a中国药科大学新药研究中心 南京 210009)
    (b中国药科大学基础部 南京 210009)
    (c中国药科大学药理教研室 南京 210009)
  • 收稿日期:2006-08-31 修回日期:1900-01-01 发布日期:2007-05-21
  • 通讯作者: 赖宜生

Synthesis and Biological Activity of 5-Chloro-3-(hydroxy- p-methanesulfonylphenylmethylene)-2-oxo-2,3-dihydroindole-1-carboxamides

LAI Yi-Sheng*,a, ZHANG Yi-Huaa, LI Yue-Zhenb, JI Huic
YANG Mingc, CONG Ri-Ganga   

  1. (a Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009)
    (b Department of Basic Pharmaceutical Sciences, China Pharmaceutical University, Nanjing 210009)
    (c Department of Pharmacology, China Pharmaceutical University, Nanjing 210009)
  • Received:2006-08-31 Revised:1900-01-01 Published:2007-05-21
  • Contact: LAI Yi-Sheng

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为了寻找高效低毒的非甾体抗炎药物, 将5-氯-2-吲哚酮与氯甲酸苯酯经酯化及水解制得1-苯氧羰基-5-氯-2-吲哚酮, 在4-N,N-二甲氨基吡啶作用下与对甲磺酰基苯甲酰氯反应, 经酸化得1-苯氧羰基-3-[羟基-(p-甲磺酰基)苯甲撑基]-5-氯-2-吲哚酮(II1), 最后与相应的胺(氨)反应, 经盐酸中和制得未见文献报道的目标化合物II2～II15, 其结构经IR, 1H NMR, MS和元素分析确证. 二甲苯致小鼠耳肿胀模型测试显示II10, II11, II15具有明显的抗炎活性; 角叉菜胶致大鼠足跖肿胀模型试验结果表明, II10, II11抗炎活性与双氯芬酸钠和替尼达普钠相当(P＞0.05); 其中II11的胃肠道副作用显著小于双氯芬酸钠(P＜0.05)和替尼达普钠(P＜0.01).

关键词: 3-(羟基-p-甲磺酰苯甲撑基)-5-氯-2-吲哚酮-1-羧酰胺, 胃肠道副作用, 合成, 抗炎活性, 替尼达普

In order to search for new compounds with stronger anti-inflammatory activity and less side effects, phenyl 5-chloro-2-oxindole-1-carboxylate, obtained from 5-chloro-2-oxindole via esterification with phenyl chloroformate and subsequent hydrolyzation, reacted with 4-(methylsulfonyl) benzoyl chloride and 4-dimethylaminopyridine, followed by acidification with hydrochloric acid to yield phenyl 5-chloro- 3-(hydroxy-p-methylsulfonylphenylmethylene)-2-oxo-2,3-dihydroindole-1-carboxylate (II1), which was condensed with corresponding amines, followed by acidification with hydrochloride acid to afford the target compounds II2～II15, respectively. Fifteen novel title compounds were synthesized, and their structures were confirmed by IR, 1H NMR, MS spectra and elemental analyses. II10, II11 and II15 exhibited marked anti-inflammatory activity in xylene-induced mice ear swelling model. Moreover, II10 and II11 showed significant anti-inflammatory activity comparable to diclofenac sodium and tenidap sodium (P＞0.05) in carrageenan-induced rat paw edema model. II11 had less gastrointestinal side effect than diclofenac sodium (p＜0.05) and tenidap sodium (P＜0.01).

Key words: 5-chloro-3-(hydroxy-p-methylsulfonylphenylmethylene)-2-oxo-2,3-dihydroindole-1- carboxamides, gastrointestinal side effect, synthesis, anti-inflammatory activity, tenidap