| Pyrimidine derivatives containing a six-membered nitrogeneous heterocycle are widely used in the fields of medicine and pesticides. Most of the pyrimidine and their derivatives are known to be associated with a wide spectrum of biological activity including insecticidal, acaricidal, fungicidal, antimicrobial, herbicidal, antiviral, and anticanceral activity. It is one of the effective measures to discover a novel family of broad-spectrum bioactivity lead compounds base on the structure modification and optimization of pyrimidine. In the study, seven series of pyrimidine derivatives containing amide, 1,2,4-oxdiazole, 1,3,4-oxdiazole, 1,3,4-thidiazole and pyrazole amide moiety were synthesized and evaluated for their fungicidal, insecticidal and anti-TMV activities. The half-maximal effective concentration(EC50) values and structure–activity relationships(SAR) of the synthesized compounds(Fig. 1) with significant anti-TMV activities were also evaluated. And the conclusions are shown as follows:1. Starting from 2-cyanoacetamide, acetimidamide hydrochloride and ethyl 4,4,4-trifluoro-3-oxobutanoate, four key intermediates inchuding 4-amino-2-methylpyrimidine-5-carbonitrile, 4-amino-N’-hydroxy-2-methylpyrimidine-5-carboximidamide, 4-amino-2-methyl-pyrimidine-5-carbohydrazide, 4-((2-methyl-6-(trifluoro-methyl)pyrimidin-4-yl)oxy)aniline were designed and synthesized. Then, seven series of pyrimidine derivatives containing amide, 1,2,4-oxdiazole, 1,3,4-oxdiazole, 1,3,4-thidiazole and pyrazole amide moiety were synthesized base on the key intermediates and their structures were characterized by IR, 1H NMR, 13 C NMR and element analysis.2. The single-crystal structure of V-26 was confirmed by X-ray crystallography. The compound V-26, belongs to Triclinic group with space group P21/c, and cell dimensions of a = 14.398(8) ?, b = 11.580(6) ?, c = 9.779(6) ?, α = 90°, β = 103.407(8)°, γ = 90°, μ = 0.551 mm-1, V = 1586.0(15) ?3, Z = 4, Dc = 1.542 gcm-3, F(000) = 752, T = 293(2)K, 1.45°<θ<25.99°, R = 0.0904,ωR=0.2207.3. The antifungal activities of some title compounds on S. sclerotiorum, P. infestans, T. cucumeris, G. zeae, F. oxysporum and C. mandshurica were tested by the mycelial growth rate method. The results of bioassay showed that most of the compounds had certain antifungal activities. The inhibition activities of compound I-1 against F. oxysporum and C. mandshurica at 50 μg/m L were 63.8% and 71.3%, respectively, which were better than that of Hymexazol(58.40% and 57.30%). Compounds I-16 and I-17 showed good inhibition activity against P. infestans at 72.0% and 59.0%, respectively, which were similar to that of Hymexazol(58.40% and 57.30%). Compound I-17 showed inhibition activity against S. sclerotiorum and G. zeae, with the inhibition rate of 66.7% and 67.7% at 50 μg/m L. And the good inhibited rate for compounds VII-3 and VII-9 aganist S. sclerotiorum, G. zeae, F. oxysporum and C. mandshurica indicated that compound VII-3(73.31%,74.62%,88.85% and 83.53%) and compound VII-9(94.25%, 78.23%, 90.35% and 82.90%) at 50 mg/m L.Insecticidal activities of some title compounds on Prodenia litura, Ostrinia furnacalis, Spider mite, Aphis craccivora Koch and Nilaparvata lugens were tested using leaf-immersing and spraying method. The results of bioassay showed that most of the compounds had certain insecticidal activities. The insecticidal activity of compounds I-15 and I-20 against Ostrinia furnacalis at 200 μg/m L were 98.3% and 100%, Compound IV-4 showed insecticidal activity against Aphis craccivora Koch, with the mortality rate of 88.9% at 200 μg/m L, Compound IV-2 displayed 74.6% activity against Nilaparvata lugens at 200 μg/m L.The half leaf method was used to determine some of the title products’ s inhibitory activity in vivo curative efficacies against tobacco mosaic virus(TMV) at the concentration of 500 μg/m L. The preliminary biological results showed that these compounds exhibited good antiviral activity against TMV in vivo. Notably, compounds V-14, V-18, VI-5, VI-11 and VI-18 exhibited excellent curative activity against TMV than Ningnanmycin, with values of 61.07%, 56.86%, 61.11%, 57.35% and 56.99%, respectively. At the same time, these compounds could inhibit TMV in vivo by approximately 50%(EC50 for curative effect) at 246.48 μg/m L, 290.98 μg/m L, 266.21 μg/m L,287.05 μg/m L and 293.59 μg/m L, respectively, which are superior to that of the commercial agent Ningnanmycin(301.83 μg/m L). Compounds V-8, V-10, V-31, VI-11 and VI-21 had protective effect against TMV at 62.05%, 66.32%, 62.03%, 67.93% and 63.86%, respectively, which was similar to that of Ningnanmycin(66.37%) at 500 μg/m L.
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