The Disease-- Thiadiazole Derivatives Of The Molecular Design, Synthesis And Biological Activity

Forty-nine novel diheterocyclic compounds containing both 1,2,3-thiadiazole and 1,2,4-triazole moieties were designed and synthesized according to the principles of combination of bioactive sub-structures on the basis of systemic conclusion of the study progress on 1,2,3-thiadiazole derivatives and 1,2,4-triazole derivatives in this thesis. All the structures of the target compounds synthesized were determined by ¹H NMR and IR, some of them were determined by elemental analysis and EI-MS, two typical crystals ofⅠ₇ andⅡ₃ were cultured and detected for structure confirmation by X-ray crystal diffraction. The title compounds can be divided into two series according to their structural characteristics as 6-substituted-3-(4-methyl-1,2,3-thiadiazolyl)-[1,2,4]triazolo-[3,4-b][1,3,4]thia-dizoles (Ⅰ) and 4-substituted imino-3-(4-methyl-1,2,3-thiadiazolyl)-1,2,4-triazole-5-thione (Ⅱ), their structures were shown as following:Preliminary biological activity screening indicated that, all the compounds showed certain degrees of fungicidal activity against most fungi tested at 50μg/mL. The growth inhibition rate of compoundsⅠ₂₄,Ⅰ₂₅,Ⅰ₂₆,Ⅰ₃₆,Ⅱ₃,Ⅱ₄,Ⅱ₆ andⅡ₁₂ against Botrytis cinerea were up to 80%.Ⅰ₂₂ exhibited good growth inhibition to most tested fungi with the growth inhibition rate against Physalospora piricola, Pellicularia sasakiimore and Rhizoctonia solani were all up to 83%, the EC₅₀ against 6 fungi were between 2.5μg/mL and 14.6μg/mL, this compound can be conducted for further studies as fungicide leading compound. While, I25 exhibited good fungicide activity against Fusarium oxysporum with growth inhibition rate of 93.0%. CompoundsⅡexhibited good fungicide activity against Botrytis cinerea, the growth inhibition of compoundⅡ₁₂ was up to 87%, compoundsⅡ₃,Ⅱ₄ andⅡ₆ had about 78% of growth inhibition, and compoundⅡ₁ had good activity against Gibberella zeae with growth inhibition of 78.7%. In vitro inhibition rate of compoundⅠ₁₁ against TMV was 53.57% at 500μg/mL, which was better than that of positive controle ribavirin did. CompoundⅠ₇ had good antivirus activity against TMV with inhibition rate of 44.44% both at 100μg/mL and 500μg/mL. Most target compounds exhibited phototoxicity to tobacco during the procedure of systemic acquired resistance activity determination. Thereafter, the herbicide activity of the target compounds were determined accordingly, the primarily bioassay showed that, compoundsⅠ₇,Ⅰ₁₂,Ⅰ₁₄,Ⅰ₁₆,Ⅰ₁₈,Ⅰ₂₁,Ⅰ₂₆,Ⅰ₃₀,Ⅰ₃₁ andⅠ₃₇ exhibited good herbicidal activity against Brassica napus, compoundsⅠ₆ andⅠ₁₁ had good activity against Echinochloa crusgalli (L.), which were equivalent with that of positive control herbicide tribenuron-methyl did at the application dosage of 10μg/mL.