Design and Syntheses of Novel Phthalazin-1(2H)-one Derivatives as Acetohydroxyacid Synthase Inhibitors

• Published in: Journal of agricultural and food chemistry Vol. 54; no. 24; pp. 9135 - 9139
• Main Authors: Li, Yuan-Xiang, Luo, Yan-Ping, Xi, Zhen, Niu, Congwei, He, Yan-Zhen, Yang, Guang-Fu
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 29.11.2006; Amer Chemical Soc
• Subjects: acetolactate synthase; Acetolactate Synthase - antagonists & inhibitors; Agriculture; Agriculture, Multidisciplinary; Arabidopsis thaliana; bioassays; Biological and medical sciences; Chemistry; Chemistry, Applied; enzyme inhibition; enzyme inhibitors; Food industries; Food Science & Technology; Fundamental and applied biological sciences. Psychology; herbicidal properties; herbicides; Herbicides - chemical synthesis; Herbicides - chemistry; heterocyclic nitrogen compounds; Humans; Life Sciences & Biomedicine; phthalazin-1(2H)-ones; Phthalazines - chemical synthesis; Phthalazines - chemistry; Phthalazines - pharmacology; Physical Sciences; Plants - drug effects; Science & Technology; Structure-Activity Relationship; synthesis; weeds; acetohydroxyacid synthase (AHAS); methylphthalazin-1-one; herbicide; HERBICIDE KIH-6127; ANALOGS; PYRIMIDIN-2-YL SALICYLATES; Design; Acetohydroxyacid synthase (AHAS); Synthesis; Enzyme; Pesticides; Inhibitor; Synthase; Herbicide
• ISSN: 0021-8561; 1520-5118
• DOI: 10.1021/jf061976j

A series of 2-substituted-8-(4,6-dimethoxypyrimidin-2-yloxy)-4-methylphthalazin-1-one derivatives, 7a−7w, were designed via an ortho-substituent cyclization strategy to discover a new herbicidal lead structure. These compounds were synthesized by a seven-step route using 3-hydroxy-acetophenone as a starting material. Determination of the Ki values against wild-type A. thaliana acetohydroxyacid synthase (AHAS) (EC 4.1.3.18) indicated that some of the compounds displayed good enzyme inhibition activity comparable to that of KIH-6127. The further preliminary bioassay data on weeds showed that the synthesized compounds exhibited typical injury symptoms of AHAS-inhibiting herbicides, and some of them showed broad-spectrum and high herbicidal activities in postemergence treatments against Echinochloa crusgalli, Digitaria sanguinalis, Setaria viridis, Brassica juncea, Amaranthus retroflexus, and Chenopodium album at an application rate of 150 g ai/ha. To our knowledge, this is the first report of methylphthalazin-1-one derivatives as AHAS inhibitors. Keywords: Acetohydroxyacid synthase (AHAS); methylphthalazin-1-one; herbicide