Novel N-Phenyltriazinone Derivatives Containing Oxazine/Oxime Fragments as Promising Protoporphyrinogen IX Oxidase...

To continue our development of novel N-phenyltriazinone herbicides, a series of N-phenyltriazinone derivatives containing 5,6-dihydro-4H-1,2-oxazine or oxime fragments were designed and synthesized based on intermediate derivatization approach using ring expansion and ring opening strategies. Nicotiana tabacum PPO (NtPPO) activity assay showed that most of the compounds showed strong inhibition to NtPPO. Among them, compound F10 (K_i = 28.9 nM) exhibits good inhibitory effect on NtPPO comparable to that of triflurazine (K_i = 30.7 nM). Systematic postemergence herbicidal activity evaluation found that F10 had excellent herbicidal activity, with over 90% control effect on six weed species (Echinochloa crusgalli, Eleusine indica, Setaria faberii, Abutilon juncea, Amaranthus retroflexus, and Portulaca oleracea) at 37.5 g a.i./ha. Moreover, it caused only 20-40% damage to rice, maize, peanuts, and wheat at 75-150 g a.i./ha, which was significantly safer than trifludimoxazin (60-100%). Molecular simulations showed that compound F10 formed two hydrogen bonds with Arg98 of NtPPO. Density functional theory (DFT) calculations indicated that F10 showed high chemical reactivity and electronic chemical potential. The present study demonstrates that compound F10 holds significant potential as a promising PPO inhibitor and it offers a novel approach for the development of efficient and broad-spectrum herbicides through an intermediate derivatization strategy.