Synthesis and Evaluation of Herbicidal UreidopyrimidineCompounds: Focus on Sulfonamide Modifications

In this study, 32 novel ureidopyrimidine compounds containing sulfonamide fragments were strategically designed and synthesized through active substructure combination. Postemergence herbicidal activity assays demonstrated that compounds <b>13a</b>, <b>14d</b>, and <b>15c</b> exhibited superior efficacy against broadleaf weeds, including <i>Zinnia elegans</i> and <i>Abutilon theophrasti</i>, with compound <b>15c</b> achieving a remarkable 95% control rate at 9.375 g a.i./ha, comparable to that of the commercial herbicide saflufenacil. Molecular docking simulations revealed that these compounds, along with saflufenacil, establish hydrogen bonds with protoporphyrinogen oxidase, particularly involving important amino acid residues, including ARG-98, GLY-175, and ASN-67. Structure–activity relationship analysis, supported by density functional theory calculations and molecular electrostatic potential studies, highlighted the importance of negatively charged regions in herbicidal activity. This comprehensive research provides valuable insights into the design and development of potent herbicides, establishing a strong foundation for future advancements in agricultural chemistry.