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

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. Compound 33 was designed based on the CoMFA and CoMSIA models, which exhibited excellent nematicidal acivity against Tylenchulus semipenetrans and was better than avermectin and fosthiazate.