S-烃基-1-烃基-3-[4-(苯并噻唑-2-巯基)苯基]异硫脲的合成及生物活性  

Synthesis and Biological Activity of S-Alkyl(or aralkyl)-1-alkyl-3-[4-(benzothiazole-2-mercapto)phenyl]isothioureas

作　　者：徐云根[1] 华维一[1] 刘晓燕[1] 朱东亚[1] 

机构地区：[1]中国药科大学新药研究中心,南京210009

出　　处：《有机化学》2004年第10期1217-1222,共6页Chinese Journal of Organic Chemistry

基　　金：国家自然科学基金 (No.39670 856)资助项目

摘　　要：以 2 巯基苯并噻唑 ( 1)为原料 ,经缩合和还原得到 2 ( 4 氨基苯硫基 )苯并噻唑 ( 3 ) ,再与异硫氰酸苯甲酰酯或异硫氰酸烃基酯反应得到取代硫脲 ( 5和 7) ,最后与卤代烃反应得到 2 0个新的S 烃基 1 烃基 3 [4 (苯并噻唑 2 巯基 )苯基 ]异硫脲化合物 ( 6和 8) ,其结构经IR ,1HNMR ,MS及元素分析确证 .初步的药理试验表明 ,2 0个目标化合物均有不同程度的iNOS抑制活性 ,化合物 8a ,8b ,8c ,8e ,8f ,8i,8j和 8k的iNOS抑制活性强于阳性对照药氨基胍 ,其中化合物 8j的iNOS抑制活性比氨基胍强 2In order to get some novel compounds with potent iNOS inhibitory activity for the treatment of septic shock and inflammation, 20 target compounds of S-alkyl (or aralkyl)-N-[4-(benzothiazole-2-mercapto)phenyl]isothioureas 6a～6i and S-alkyl (or aralkyl)-1-alkyl-3- [4-(benzothiazole-2-mercapto)phenyl]isothioureas 8a～8k were synthesized by two different synthetic methods from 2-mercaptobenzothiazole (1). 6a～6i were synthesized from 2-(4- aminophenylmercapto)benzothiazole (3) by the reaction with benzoyl isothiocyanate to form corresponding benzoylthioureas 4 which was hydrolyzed with 10% sodium hydroxide solution, followed by S-alkylation with alkyl iodide or (substituted)benzyl halide. 8a～8k were synthesized from compound 3 by the reaction with alkyl(or aryl) isothiocyanate to form corresponding 1,3-disubstituted thioureas 7 which was S-alkylated with alkyl iodide or (substituted) benzyl halide. The intermediate 3 was synthesized from 2-mercaptobenzothiazole (1) by the reaction with 1-chloro-4-nitrobenzene to form 2-(4-nitrophenylmercapto)benzothiazole (2) which was reduced by iron powder and hydrochloric acid. The structures of the obtained compounds were confirmed by IR, MS, 1H NMR soectra and elemental analysis. The results of preliminary pharmacological test showed that all these compounds possessed iNOS inhibitory activity, among which compounds 8a, 8b, 8c, 8e, 8f, 8i, 8j and 8k had stronger activity than the control aminoguanidine. Activity of compound 8j is 26 times more potent than aminoguanidine.

关 键 词：S-烃基-1-烃基-3-[4-(苯并噻唑-2-巯基)苯基]异硫脲 合成 生物活性 一氧化氮合酶抑制剂 

分 类 号：O626[理学—有机化学]