Design, Synthesis, and Herbicidal Activity Study of Novel Pyrazole-Carboxamides as Potential Transketolase Inhibitors

Transketolase (TKL; EC 2.2.1.1) has been identified as a potential new herbicide target. In order to discover highly herbicidal active compounds targeting TKL and improve their structural diversity for lead compounds, a series of pyrazole-carboxamides <b>7a</b>-<b>7v</b> were designed and synthesized through structural optimization for pyrazole-containing phenoxy amide compound <b>4u</b>. Among the synthesized compounds, compound <b>7r</b> possessed excellent herbicidal efficacy against <i>Digitaria sanguinalis</i> (<i>Ds</i>) and <i>Amaranthus retroflexus</i> (<i>Ar</i>) by the small cup method (the inhibition about 95%, 100 mg/L) and the foliar spray method (the inhibition over 90%, 150 g ai/ha) in a greenhouse, which were superior to that of the positive control nicosulfuron. More significantly, compound <b>7r</b> displayed good crop selectivity toward both maize and wheat even at 375 g of ai/ha. The studies on mode of action (MOA) of high herbicidal active compounds, including the enzyme inhibition activity, fluorescent quenching experiments, and molecular docking analysis between <i>Setaria viridis</i> (<i>Sv</i>)TKL and ligand, suggested that compound <b>7r</b> acts as a typical TKL inhibitor, and the benzothiazole ring is an important motif for <i>Sv</i>TKL inhibition activity. Above all, compound <b>7r</b> could be a potential candidate for the development of herbicides with new MOA for weed control in maize and wheat field.