Novel <i>N</i>-Phenyltriazinone Derivatives Containing Oxazine/Oxime Fragments as Promising Protoporphyrinogen IX Oxidase Inhibitors

To continue our development of novel <i>N</i>-phenyltriazinone herbicides, a series of <i>N</i>-phenyltriazinone derivatives containing 5,6-dihydro-4<i>H</i>-1,2-oxazine or oxime fragments were designed and synthesized based on intermediate derivatization approach using ring expansion and ring opening strategies. <i>Nicotiana tabacum</i> PPO (<i>Nt</i>PPO) activity assay showed that most of the compounds showed strong inhibition to <i>Nt</i>PPO. Among them, compound <b>F10</b> (<i>K_i</i> = 28.9 nM) exhibits good inhibitory effect on <i>Nt</i>PPO comparable to that of triflurazine (<i>K_i</i> = 30.7 nM). Systematic postemergence herbicidal activity evaluation found that <b>F10</b> had excellent herbicidal activity, with over 90% control effect on six weed species (<i>Echinochloa crusgalli</i>, <i>Eleusine indica</i>, <i>Setaria faberii</i>, <i>Abutilon juncea</i>, <i>Amaranthus retroflexus</i>, and <i>Portulaca oleracea</i>) 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 <b>F10</b> formed two hydrogen bonds with Arg98 of <i>Nt</i>PPO. Density functional theory (DFT) calculations indicated that <b>F10</b> showed high chemical reactivity and electronic chemical potential. The present study demonstrates that compound <b>F10</b> 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.