S-烃基-1-烃基-3-[4-(苯并咪唑-2-巯基)苯基]异硫脲的合成及其iNOS抑制活性  

Synthesis and iNOS Inhibitory Activity of S-Alkyl(or aralkyl)-1-alkyl (or aryl)-3-[4-(benzimidazole-2-mercapto)phenyl] Isothioureas

作　　者：徐云根[1] 华维一[1] 朱东亚[1] 时煜[1] 封小琴[1] 

机构地区：[1]中国药科大学新药研究中心,南京210009

出　　处：《高等学校化学学报》2003年第12期2208-2214,共7页Chemical Journal of Chinese Universities

基　　金：国家自然科学基金 (批准号 :3 9670 85 6)资助

摘　　要：以 2 -巯基苯并咪唑 ( 1 )为原料 ,经缩合和还原得到 2 -( 4 -氨基苯硫基 )苯并咪唑 ( 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-(苯并咪唑 -2 -巯基 )苯基 ]异硫脲化合物 ( 6和 8) ,其结构经 IR,1H NMR,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 i NOS抑制活性 ,其中化合物 6b,8d和 8f的 i NOS抑制活性与阳性对照药氨基胍相当 .In order to get some novel potent compounds with iNOS inhibitory activity for the treatment of septic shock and inflammation, 20 target compounds of S-alkyl(or aralkyl)-N-[4-(benzimidazole-2-mercapto) phenyl] isothioureas(6a-6j) and S-alkyl(or aralkyl)-1-alkyl(or aryl)-3-[4-(benzimidazole-2-mercapto) phenyl] isothioureas(8a-8j) were synthesized by two different synthetic methods from 2-mercaptobenzimidazole(1). Compounds 6a-6j were synthesized from 2-(4-aminophenylmercapto) benzimidazole(3) by reaction with benzoyl isothiocyanate to form the corresponding benzoylthioureas 4 which was hydrolyzed with 2.0 mol/L sodium hydroxide solution containing tetrahydrofuran, followed by S-alkylation with alkyl iodide or (substituted) benzyl halogen. Compounds 8a-8j were synthesized from compound 3 by reaction with alkyl(or aryl) isothiocyanate to form the corresponding 1,3-disubstituted thioureas 7 which was S-alkylated with alkyl iodide or (substituted) benzyl halogen. The intermediate 3 was synthesized from 2-mercaptobenzimidazole(1) by reaction with 1-chloro-4-nitrobenzene to form 2-(4-nitrophenylmercapto)benzimidazole(2) which was reduced by iron powder and hydrochloric acid. The structures of these compounds were confirmed by IR, MS, 1H NMR and elemental analysis. The results of preliminary pharmacological test show that most of these compounds possess iNOS inhibitory activity, among which compounds 6b, 8d and 8f have a comparable activity to the control aminoguanidine.

关 键 词：S-烃基-1-烃基-3-[4-(苯并咪唑-2-巯基)苯基]异硫脲 合成 INOS抑制剂 抑制活性 败血性休克 炎症 

分 类 号：R914.4[医药卫生—药物化学]