Synthesis, Nematicidal Activity, and 3D‐QSAR of Novel 1,3,4‐Oxadiazole/ Thiadiazole Thioether Derivatives

Abstract

Forty one novel 1,3,4‐oxadiazole/thiadiazole thioether derivatives containing phenoxy moiety were designed and synthesized. Bioassay demonstrated that some of them showed remarkable activities against Tylenchulus semipenetrans in vitro and in vivo. Compounds 20, 21, 35 and 39 showed excellent lethal activities after treatment for 48 h in vitro, with LC50 values of 13.4 ± 1.8, 11.7 ± 2.5, 13.7 ± 2.4 and 13.3 ± 1.1 mg·L–1, respectively, which were obviously superior to fosthiazate (49.1 ± 2.8 mg·L–1) and avermectin (26.6 ± 2.3 mg·L–1). Compound 21 can effectively control the citrus nematode disease caused by T. semipenetrans at 200 mg·L–1 in vivo with (68 ± 3)% inhibitory effect, which was even better than that of avermectin ((63 ± 2)%). The CoMFA and CoMSIA models of three‐dimensional quantitative structure‐activity relationships (3D‐QSARs) were established. The compound 33 was designed based on the 3D‐QSAR models with more vigorous nematicidal activities in vitro (LC50 = 9.8 ± 1.4 mg·L–1) and in vivo ((70 ± 5)%). These results demonstrated that compound 33 can be considered as a potential nematicide.

Synthesis, Bioactivity Evaluation,3D‐QSAR, and Molecular Docking of Novel Pyrazole‐4‐carbohydrazides as Potential Fungicides Targeting Succinate Dehydrogenase

“…indicated the reliable predictive accuracy of 3D‐QSAR models. [ 33‐36 ] Contour maps for the CoMFA and CoMSIA models were displayed in Figure 4. Actual and predicted pEC 50 values for the training set and test set were reported in Table 2, and the correlation plots of CoMFA and CoMSIA models were shown in Figure 5.…”

“…The crystal data of compound 7j were measured with graphite‐monochromatized Mo Kα radiation ( λ = 0.71073 Å) at 296 (2) K. The crystal structure was solved by direct methods using SHELXS‐97 and refined with SHELXL of the SHELXTL package. [ 36 ]…”

“…3D‐QSAR research reveals the mode of binding of drug molecules and biological macromolecules by calculating the physical and chemical properties and structural parameters of compounds, and predicts or explains the pharmacological activity of small organic molecules. [ 33‐36 ] Therefore, based on the results of 3D‐QSAR research, analyzing the characteristics of receptors or pharmacological targets to rationally design new molecular skeletons is a very important drug molecular design strategy. According to our previous investigation on the pyrazole derivatives and corresponding 3D‐QSAR model, we found that the positive charge groups and hydrogen bond acceptors are favored at hydrazone position to improve the antifungal activity (Figure 1).…”

Synthesis and Antibacterial Evaluation of Novel 1,3,4-Oxadiazole Derivatives Containing Sulfonate/Carboxylate Moiety

“…So, it is urgent to develop efficient new chemical pesticides to deal with this problem. We previously found that 1,3,4-oxadiazole derivatives have a variety of biological effects, including antibacterial [11][12][13], antifungal [14,15], antiviral [16], nematocidal [17] and insecticidal [18,19] activity. 1,3,4-oxadiazole has the ideal heterocyclic structure to be developed into efficient pesticides.…”

“…White liquid; yield, 80.5%;1 H NMR (400 MHz, CDCl 3 ) δ 7.81-7.75 (m, 2H, Ar-H), 7.50-7.45 (m, 2H, Ar-H), 5.19 (s, 2H, -CH 2 -),4.72 (t, J = 5.7 Hz, 1H, -CH-),4.60 (t, J = 5.7 Hz, 1H, -CH-),3.49 (t, J = 5.7 Hz, 1H, -CH-),3.43 (t, J = 5.7 Hz, 1H, -CH-) 13. C NMR (100 MHz, CDCl 3 ) δ 166 17,. 160.81, 141.37, 133.62, 129.81, 129.51, 80.62 (d, J = 172.1 Hz), 59.74, 32.33 (d, J = 22.2 Hz).…”