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有机化学
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有机化学 ›› 2004, Vol. 24 ›› Issue (2): 210-215. 上一篇    下一篇

研究论文

S-烃基-1-烃基-3-[4-(5-取代苯并咪唑-2-巯基)苯基]异硫脲的合成及生物活性

徐云根, 罗穗†, 华维一*, 朱东亚   

  1. 中国药科大学新药研究中心 南京 210009
  • 收稿日期:2003-05-06 修回日期:2003-08-04 接受日期:2003-09-01 发布日期:2022-09-20
  • 作者简介:†现在广东省药品监督管理局工作.
  • 基金资助:
    国家自然科学基金(No. 39670856)资助项目.†现在广东省药品监督管理局工作

Synthesis and Biological Activity of S-Alkyl (or Aralkyl)-1-alkyl (or aryl)-3- [4-(5-methoxy (or chloro)benzimidazole-2-mercapto)phenyl]isothioureas

XU, Yun-Gen, LUO, Sui†, HUA, Wei-Yi*, ZHU, Dong-Ya   

  1. Center of Drug Discovery, China Pharmaceutical University, Nanjing 210009
  • Received:2003-05-06 Revised:2003-08-04 Accepted:2003-09-01 Published:2022-09-20
  • Contact: * E-mail: huawy36@yahoo.com.cn

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以5-甲氧基(或氯)-2-巯基苯并咪唑(1)为原料,经缩合和还原得到5-甲氧基(或氯)-2-(4-氨基苯硫基)苯并咪唑(3),再与异硫氰酸烃基酯反应得到取代硫脲4,最后与卤代烃反应得到12个新的S-烃基-1-烃基-3-[4-(5-甲氧基(或氯)苯并咪唑-2-巯基)苯基]异硫脲化合物5.其结构经IR, 1HNMR, MS及元素分析确证.初步的药理试验表明,12个目标化合物的iNOS抑制活性均强于阳性对照药氨基胍.

关键词: iNOS抑制剂, 异硫脲, 炎症, 败血性休克

In order to get some novel compoundswith potent iNOS inhibitory activity for the treatment of septic shock and inflammation, 12 target compounds of S-alkyl (or aralkyl)-1-alkyl (or aryl)-3-[4-(5-methoxy (or chloro)-benzimidazole-2-mercapto)phenyl]isothioureas(5a～5l) were synthesized. Firstly, 2-mercapto-5-methoxy (or chloro)benzimidazole (1) were converted into 5-methoxy (or chloro)-2-(4-nitrophenylmercapto)benzimidazole (2) by condensation with 1-chloro-4-nitrobenzene. Secondly, reductionof 2 afforded 5-methoxy (or chloro)-2-(4-aminophenylmercapto)benzimidazole (3). Then 3 were converted into corresponding 1,3-disubstituted thioureas 4 by reaction with alkyl (or aryl) isothiocyanate. Finally, the S-alkylation of 4 with alkyl iodide or (substituted)benzyl halogen was carried out to obtain the targetcompounds 5a～5l. The structures of the compounds were confirmed by IR, MS, 1H NMR spectra and elemental analysis. Theresults of preliminary pharmacological test showed that all of compounds possess higher iNOS inhibitory activity than the control aminoguanidine.

Key words: iNOS inhibitor, isothiourea, inflammation, septic shock