关键词: iNOS抑制剂, 异硫脲, 2-(4-氨基苯硫基)苯并噻唑, 败血性休克

In 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 withbenzoyl 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 thereaction 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. Activityof compound 8j is 26 times more potent thanaminoguanidine.

Key words: iNOS inhibitor, isothiourea, 2-(4-aminophenylmercapto)benzothiazole, septic shock