Abstract: 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 benzoyLIsothiocyanate to form the corresponding benzoylthioureas 4 which was hydrolyzed with 2.0 mol/Lsodium hydroxide solution containing tetrahydrofuran, followed by S-alkylation with alkyLIodide 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 alkyLIodide 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, ¹HNMR 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.

Key words: iNOS inhibitor, Isothiourea, 2-(4-Aminophenylmercapto)benzimidazole, Septic shock