State Key Laboratory of Elemento-Organic Chemistry, Nankai University, No. 94 Weijin Road, Nankai District, Tianjin 300071, People's Republic of China.
J Agric Food Chem. 2010 Mar 10;58(5):2630-6. doi: 10.1021/jf9029628.
Heterocyclic compounds play an important role as the main sources of lead molecules of agrochemicals. Synthesis and biological activity of thiadiazole-containing 1,2,4-triazolo[3,4-b][1,3,4]-thiadiazoles were seldom reported. To find novel lead compounds with various biological activities, a series of 6-substituted-3-(4-methyl-1,2,3-thiadiazolyl)[1,2,4]triazolo[3,4-b][1,3,4]thiadizoles were rationally designed and synthesized according to the principle of combinations of bioactive substructures by the condensation of 3-(4-methyl-1,2,3-thiadiazolyl)-4-amino-1,2,4-triazole-5-thione with various carboxylic acids and phosphorus oxychloride. All newly synthesized compounds were identified by proton nuclear magnetic resonance ((1)H NMR), infrared spectroscopy (IR), electroionization mass spectrometry (EI/MS), and elementary analysis. The crystal structure of 3-(4-methyl-1,2,3-thiadiazolyl)-6-(4-methylphenyl)[1,2,4]triazolo[3,4-b][1,3,4]thiadizole was determined by X-ray diffraction crystallography. In this crystal, two intermolecular hydrogen bonds (N2...H-C12 and N3...H-C13), a weak intermolecular interaction (S...S), and the weak ppi-ppi intermolecular interaction were observed. Fungicide screening indicated that all of the target compounds showed certain extent of growth inhibition against fungi tested. 3-(4-Methyl-1,2,3-thiadiazolyl)-6-n-propyl[1,2,4]triazolo[3,4-b][1,3,4]thiadizole and 3-(4-methyl-1,2,3-thiadiazolyl)-6-trichloromethyl[1,2,4]triazolo[3,4-b][1,3,4]thiadizole were found to have potential wide spectrum of fungicide activity. The median effective concentrations (EC(50)) detected for 3-(4-methyl-1,2,3-thiadiazolyl)-6-trichloromethyl[1,2,4]triazolo[3,4-b][1,3,4]thiadizole to six fungi were from 7.28 micromol/L against Pellicularia sasakii (Shirai) to 42.49 micromol/L against Alternaria solani . The results indicated that thiadiazole-containing 1,2,4-triazolo[3,4-b][1,3,4]-thiadiazoles were potential fungicide lead compounds.
杂环化合物作为农用化学品的主要先导分子源,具有重要的作用。含噻二唑的 1,2,4-三唑并[3,4-b][1,3,4]噻二唑的合成和生物活性很少有报道。为了寻找具有各种生物活性的新型先导化合物,根据生物活性亚结构组合的原理,通过 3-(4-甲基-1,2,3-噻二唑基)-4-氨基-1,2,4-三唑-5-硫酮与各种羧酸和氧氯化磷的缩合,设计并合成了一系列 6-取代-3-(4-甲基-1,2,3-噻二唑基)[1,2,4]三唑并[3,4-b][1,3,4]噻二唑。所有新合成的化合物均通过质子核磁共振((1)H NMR)、红外光谱(IR)、电喷雾质谱(EI/MS)和元素分析进行鉴定。通过 X 射线衍射晶体学确定了 3-(4-甲基-1,2,3-噻二唑基)-6-(4-甲基苯基)[1,2,4]三唑并[3,4-b][1,3,4]噻二唑的晶体结构。在这个晶体中,观察到两个分子间氢键(N2...H-C12 和 N3...H-C13)、一个弱分子间相互作用(S...S)和弱 ppi-ppi 分子间相互作用。杀菌剂筛选表明,所有目标化合物对测试真菌均显示出一定程度的生长抑制作用。3-(4-甲基-1,2,3-噻二唑基)-6-正丙基[1,2,4]三唑并[3,4-b][1,3,4]噻二唑和 3-(4-甲基-1,2,3-噻二唑基)-6-三氯甲基[1,2,4]三唑并[3,4-b][1,3,4]噻二唑被发现具有潜在的广谱杀菌剂活性。对六种真菌的 3-(4-甲基-1,2,3-噻二唑基)-6-三氯甲基[1,2,4]三唑并[3,4-b][1,3,4]噻二唑的半数有效浓度(EC(50))检测值从 7.28μmol/L 对梨皮小尾孢菌到 42.49μmol/L 对茄链格孢菌不等。结果表明,含噻二唑的 1,2,4-三唑并[3,4-b][1,3,4]-噻二唑是潜在的杀菌剂先导化合物。