Synthesis of 1-acyl-2-alkylthio-1,2,4-triazolobenzimidazoles with antifungal, anti-inflammatory and analgesic effects.

Some new derivatives of 1,2,4-triazolo[2,3-a]benzimidazoles were synthesized through the reaction of 1,2-diaminobenzimidazole with carbon disulfide. The resulting 1,2,4-triazolo[2,3-a]benzimidazole-2-thione intermediate reacted with one equivalent of the alkyl halide to give the corresponding 2-alkylthio derivative 3a-g. The latters were acylated to afford the 1-acyl-2-alkylthio-1,2,4-triazolo[2,3-a]-benzimidazole derivatives 4-10 in good yields. Structures of the new compounds were verified on the basis of spectral and elemental methods of analyses. Fourteen of the prepared compounds were tested for their possible antifungal activities. Most of the tested compounds showed activity against Candida albicans and Fusarium oxysporum comparable to that of fluconazole as a reference drug. Compounds 8a, 9a, and 10d are the most active ones against most of the fungi used. Compounds 3e, 4d, 5d, 6d, 7d, 8c, 8d, 9d, and 10d were tested for their anti-inflammatory and analgesic effects; most of these compounds showed potent and significant results compared to indomethacin. Moreover, ulcerogenicity and the median lethal dose (LD(50)) of the most active compound 8d were determined in mice; LD(50) was found to be 275 mg kg(-1) (i.p.).