Design,Synthesis And Biological Activity Of Novel 1,2,4-Triazole And Pyrimidine Derivatives

1,2,4-Triazole and pyrimidine derivatives represent two interesting classes of compounds possessing a wide spectrum of biological activities, such as antibacterial, insecticide, herbicide, antivirus, antiinflammatory, antitumor, anticonvulsant and antiviral activities. In order to search for novel 1,2,4-triazole and pyrimidine derivatives with high activities, according to the bioisosterism and the connecting principle of actively biological groups, fifty-five 1,2,4-triazole and pyrimidine derivatives that representing three series were designed and synthesized in good yields. The structures of these molecule are shown in Scheme 1.ⅡⅢⅣa-eⅣf-k Schemel Parent structures of moleculeⅡ、ⅢandⅣThe synthetic methods, bioactivities, structure-activity relationship and spectral properties were studied, and many of them were found to show antibacterial-or-antitumor activities. The results are summarized as follows:1. The research progress of 1,2,4-triazole and pyrimidine derivatives are summarized in the paper. The review describes in detail their main regularities of the structure-activity relationship, fungicidal activity or antitumor activity, and biochemical mode of action.2. Fifty-five 1,2,4-triazole and pyrimidine derivatives were designed and synthesized by multiple step synthetic procedures. Their structures were characterized by 1H NMR, MS spectroscopies and element quantitative analysis. These compounds are summsaized as follow:Ⅱa～Ⅱff:3-substituted thio-4-(1,3-dione isoindoline)-5-alkyl-4H-1,2,4-triazole (32 compounds)ⅡaⅡbⅡeⅡdⅡeⅡfⅡgⅡhⅡiⅡjⅡkⅡlⅡmⅡnⅡoⅡpⅡqⅡrⅡsⅡt ⅡuⅡvⅡwⅡxⅡyⅡzⅡaaⅡbbⅡccⅡddⅡeeⅡffⅢa～Ⅲ1:(E)-N-substituted benzylidene-3-(substituted thio)-5-(3,4,5-trimethoxyphenyl)-4H-1,2,4-triazol-4-amine (12 compounds)ⅢaⅢbⅢeⅢdⅢeⅢfⅢgⅢhⅢiⅢjⅢkⅢl Ⅳa～Ⅳe:N4-substituted phenyl-N2-[1-(methylsulfonyl)piperidin-4-yl]-5-nitropyrimidine-2,4-diamine (5 compounds)ⅣaⅣbⅣcⅣdⅣeⅣf～Ⅳk:N-substituted phenyl-2-(4-methylpiperazin-1-yl)-5-nitropyrimidin-4-amine (6 compounds)ⅣfⅣgⅣhⅣiⅣjⅣk3. The results of bioactivity assay indicated that many compounds displayed antibacterial activity against Colletotrichum musae、Fusarium oxysporum f. sp. cubense、Colletotrichum gloeosporioides PenZ、Botryodiplodia theobromae、Fusarium oxysporum f. sp. niveum、Phyricularia oryzae Cav by the mycelial growth rate method at the concentration of 150 mg/L, such asⅡz、Ⅱbb、Ⅱdd、Ⅱff showed 95%,98%,92%,90% fungicidal activity against Botryodiplodia theobromae (Tab.1). Tab.1 The inhibition for fungis of compoundsⅡz、Ⅱbb、Ⅱdd、ⅡffThe antifungal activities of the 1,2,4-triazoles compounds in vitro were evaluated using two kinds of pathogenic fungi. All the compounds showed no or low inhibition of E. coli fungi, but some compounds showed antifungal activities for S. aureus at the concentration of 10 mg/L.By the MTT assay, we screen the antitumor activity of synthesized compounds on HepG2、MKN45、MCF-7、HT-29 tumor cells and find several kinds of lead compounds with antitumor activity. The IC50 of compoundⅢb against HepG2、MKN45 tumor cell lines are 7.4μM, and the IC50 of compoundⅢl against MCF-7、HepG2. MKN45 tumor cell lines are 10.9μM,10.9μM,13.7μM, respectively. The IC50 of compound IVb against MCF-7 tumor cell lines are 13.6μM, which indicated that the1,2,4-triazole or pyrimidine scaffold could be identified as a novel antitumor lead structure (Tab.2).Tab.2 antitumor activities of compoundsⅢb,Ⅲl,Ⅳb (μmol/L)...