4-Hydroxyphenylpyruvate dioxygenase (HPPD) is an important target for the development of new herbicides. HPPD inhibitors can hinder photosynthesis and induce weed death with bleaching symptoms. To explore the novel skeleton of HPPD inhibitors, a series of novel pyrazole amide derivatives were synthesized and evaluated for their inhibitory effects on Arabidopsis thaliana HPPD (AtHPPD) and herbicidal activities. Some compounds had excellent inhibitory activities against AtHPPD. Among them, compound B5 displayed top-rank inhibitory activity against AtHPPD with an IC₅₀ value of 0.04 μM, which was obviously superior to that of topramezone (IC₅₀ value of 0.11 μM). Furthermore, compounds B2 and B7 had 100% herbicidal activities in Petri dish assays against Portulaca oleracea and Amaranthus tricolor at 100 μg/mL. In particular, compound B7 not only possessed strong AtHPPD inhibitory activity but also exhibited significant preemergence herbicidal activity. However, compound B7 was completely harmless to soybean, cotton, and wheat. In addition, the molecular docking and microscale thermophoresis measurement experiment verified that compounds can bind well with AtHPPD via π–π interactions. The present work provides a new approach for the rational design of more effective HPPD inhibitors, and pyrazole amides could be used as useful substructures for the development of new HPPD inhibitors and preemergence herbicidal agents.

中文翻译：

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新型吡唑酰胺作为潜在的 4-羟基苯丙酮酸双加氧酶抑制剂

4-羟基苯丙酮酸双加氧酶（HPPD）是开发新型除草剂的重要靶点。HPPD 抑制剂会阻碍光合作用并导致杂草死亡并出现白化症状。为探索HPPD抑制剂的新骨架，合成了一系列新型吡唑酰胺衍生物，并对其对拟南芥HPPD（At HPPD）的抑制作用和除草活性进行了评价。一些化合物对At HPPD具有优异的抑制活性。其中，化合物B5对At HPPD的抑制活性位居前列，IC ₅₀值为0.04 μM，明显优于topramezone（IC ₅₀值为 0.11 μM）。此外，化合物B2和B7在 100 μg/mL的培养皿试验中对马齿苋和三色苋具有 100% 的除草活性。特别是化合物B7不仅具有很强的At HPPD抑制活性，而且表现出显着的芽前除草活性。然而，化合物B7对大豆、棉花和小麦完全无害。此外，分子对接和微尺度热泳测量实验验证了化合物可以通过以下途径与At HPPD很好地结合。π-π 相互作用。目前的工作为合理设计更有效的 HPPD 抑制剂提供了一种新方法，吡唑酰胺可用作开发新的 HPPD 抑制剂和芽前除草剂的有用子结构。