Design, Synthesis,\nand Herbicidal Activity Study of\nNovel Pyrazole-Carboxamides as Potential Transketolase Inhibitors

Transketolase (TKL; EC 2.2.1.1) has been identified as\na potential\nnew herbicide target. In order to discover highly herbicidal active\ncompounds targeting TKL and improve their structural diversity for\nlead compounds, a series of pyrazole-carboxamides <b>7a</b>–<b>7v</b> were designed and synthesized through structural optimization\nfor pyrazole-containing phenoxy amide compound <b>4u</b>. Among\nthe synthesized compounds, compound <b>7r</b> possessed excellent\nherbicidal efficacy against Digitaria sanguinalis (<i>Ds</i>) and Amaranthus retroflexus (<i>Ar</i>) by the small cup method (the inhibition about\n95%, 100 mg/L) and the foliar spray method (the inhibition over 90%,\n150 g ai/ha) in a greenhouse, which were superior to that of the positive\ncontrol nicosulfuron. More significantly, compound <b>7r</b> displayed good crop selectivity toward both maize and wheat even\nat 375 g of ai/ha. The studies on mode of action (MOA) of high herbicidal\nactive compounds, including the enzyme inhibition activity, fluorescent\nquenching experiments, and molecular docking analysis between Setaria viridis (<i>Sv</i>)TKL and ligand,\nsuggested that compound <b>7r</b> acts as a typical TKL inhibitor,\nand the benzothiazole ring is an important motif for <i>Sv</i>TKL inhibition activity. Above all, compound <b>7r</b> could\nbe a potential candidate for the development of herbicides with new\nMOA for weed control in maize and wheat field.