Design, Synthesis, and Herbicidal Activity of Novel Tetrahydrophthalimide Derivatives Containing Oxadiazole/Thiadiazole Moieties.

Protoporphyrinogen oxidase (PPO, EC 1.3.3.4) has a high status in the development of new inhibitors. To develop novel and highly effective PPO inhibitors, active substructure linking and bioisosterism replacement strategies were used to design and synthesize novel tetrahydrophthalimide derivatives containing oxadiazole/thiadiazole moieties, and their inhibitory effects on PPO (PPO) and herbicidal activity were evaluated. Among them, compounds ( = 9.05 nM) and ( = 10.23 nM) showed significantly better inhibitory activity against PPO than that against flumiclorac-pentyl ( = 46.02 nM). Meanwhile, compounds and were 100% effective against three weeds (, , and ) at 37.5 g a.i./ha. It was worth observing that compound was more than 90% effective against three weeds (, , and ) at 18.75 and 9.375 g a.i./ha. It was also safer to rice, maize, and wheat than flumiclorac-pentyl at 150 g a.i./ha. In addition, the molecular docking results showed that compound could stably bind to PPO and it had a stronger hydrogen bond with Arg98 (2.9 Å) than that of flumiclorac-pentyl (3.2 Å). This research suggests that compound could be used as a new PPO inhibitor, and it could help control weeds in agricultural production.