Design, Synthesis and Herbicidal Activity of 5-(1-Amino-4-phenoxybutylidene)barbituric Acid Derivatives Containing an Enamino Diketone Motif

In continuation of our efforts to identify novel herbicide lead compounds, twenty new 5-(1-amino-4-phenoxybutylidene)barbituric acid derivatives containing an enamino diketone motif were synthesized and evaluated for their herbicidal activities. The greenhouse bioassay results indicated that several of the target compounds, including <b>BA-1</b>, <b>BA-2</b>, <b>BA-5</b>, <b>BA-18</b>, and <b>BA-20</b>, exhibited notable post-emergence herbicidal activity, with sum inhibition rates exceeding 70% at a dosage of 150 g ha^-1, which was superior to that of the commercial herbicide flumiclorac-pentyl (FP). The structure-activity relationship analysis demonstrated that the steric and electronic effects of the R group, as well as the lipophilicity of the target compounds, significantly influenced herbicidal activity. Among these, <b>BA-1</b> was identified as a promising herbicide lead compound due to its high total herbicidal efficacy, broad-spectrum activity, and favorable crop safety profile. Molecular simulation studies indicated that <b>BA-1</b> binds effectively to <i>Nicotiana tabacum</i> protoporphyrinogen IX oxidase (<i>Nt</i>PPO), suggesting its potential as a novel PPO inhibitor. This study highlights <b>BA-1</b> as a promising lead compound for the development of novel PPO-inhibiting herbicides.