Design, synthesis and herbicidal activity study of aryl 2,6-disubstituted sulfonylureas as potent acetohydroxyacid synthase inhibitors

Bioorg Med Chem Lett. 2017 Aug 1;27(15):3365-3369. doi: 10.1016/j.bmcl.2017.06.007. Epub 2017 Jun 3.

Abstract

A series of sulfonylurea derivatives containing a 2,6-disubstituted aryl moiety were designed, synthesized and evaluated for their herbicidal activities. Most of these compounds showed excellent inhibitory rates against both monocotyledonous and dicotyledonous weeds, especially 10a, 10h and 10i. They exhibited equivalent or superior herbicidal efficiency than commercial chlorsulfuron at the dosage of 15g/ha and the preliminary SAR was summarized. In order to illuminate the molecular mechanism of several potent compounds, their apparent inhibition constant (Kiapp) of Arabidopsis thaliana acetohydroxyacid synthase (AHAS) were determined and the results confirmed that these compounds were all potent AHAS inhibitors. 10i have a Kiapp of 11.5nM, which is about 4 times as potent as chlorsulfuron (52.4nM).

Keywords: Acetohydroxyacid synthase (AHAS); Apparent inhibition constant (K(i)(app)); Herbicidal activity; Sulfonylureas.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acetolactate Synthase / antagonists & inhibitors*
  • Acetolactate Synthase / metabolism
  • Arabidopsis / drug effects*
  • Arabidopsis / enzymology
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Herbicides / chemical synthesis
  • Herbicides / chemistry
  • Herbicides / pharmacology*
  • Molecular Structure
  • Structure-Activity Relationship
  • Sulfonylurea Compounds / chemical synthesis
  • Sulfonylurea Compounds / chemistry
  • Sulfonylurea Compounds / pharmacology*

Substances

  • Enzyme Inhibitors
  • Herbicides
  • Sulfonylurea Compounds
  • Acetolactate Synthase