Synthesis And Biological Activities Of Pyrimidine Thioether Compounds

Pyrimidine thioether compounds have been widely used in pesticidal and medical fields because of their good boilogical activities.With 4,6-dimethyl-pyrimidin-2-thiol as a lead compound,13 novel 2-?benzylthio?-5-???4,6-dimethylpyrimidin-2-yl?thio?methyl?-1,3,4-oxadiazoles,15 novel2-?benzylthio?-5-???4,6-dimethylpyrimidin-2-y-l?thio?methyl?-1,3,4-thiadi-azoles,10 novel 2-??5-???4,6-dimethylpyrimidin-2-yl?thio?methyl?-1,3,4-thiadiazol-2-yl?thio?-N-phenylacetamides and 13 novel 2-???5-?benzylthio?-4-phenyl-4H-1,2,4-triazol-3-yl?methyl?thio?-4,6-dimethyl pyrimidines were designed and synthesized.Their structures were confirmed by ¹H NMR and IR.The biological activities of compounds5a-5i and 7a-7k were evaluated.The results showed that some of them had fungicidal activity and some of them exhibited significant in vitro activity against intracellular amastigotes of Leishmania donovani.The main contents are listed as follows:1.With 4,6-dimethyl pyrimidine-2-thiol as the starting materials,fifty-one novel pyrimidine thioether-linked 1,3,4-thiadiazole?oxadiazole?,or 1,2,4-triazole compounds were synthesized by the esterification,hydrazine,cyclization and the last benzylation reaction.2.The fungicidal activities results showed that 5b?5f?5g and 7a?7c?7i had certain activity against Colletrotichum acutatum?ColletrotichumfragariaeandColletrotichumgloeosporioides.Compounds 5f?5g?7a and 7i had good activities against these 3 kinds of test targets in mcrotiter conditions.The results of in vitro activity against intracellularamastigotes of Leishmania donovani showed that compounds5a?5g?5i and 7i were found highly active with IC₅₀.The activity of these compounds was far better than the reference drugs sodium stibogluconate(IC₅₀=57.3?g/mL)and paromomycin(IC₅₀=24.8?g/m L).And the bio-activity of compounds 7a?7c?7f and 7g was higher than that of the reference drugssodium stibogluconate(IC₅₀=57.3?g/mL).