title: Design and syntheses of novel phthalazin-1(2H)-one derivatives as acetohydroxyacid synthase inhibitors.
abstract: 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.
authors.affiliation: Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan, Hubei 430079, People's Republic of China.
authors.forename: Yuan-Xiang
authors.initials: YX
authors.lastname: Li
authors.forename: Yan-Ping
authors.initials: YP
authors.lastname: Luo
authors.forename: Zhen
authors.initials: Z
authors.lastname: Xi
authors.forename: Congwei
authors.initials: C
authors.lastname: Niu
authors.forename: Yan-Zhen
authors.initials: YZ
authors.lastname: He
authors.forename: Guang-Fu
authors.initials: GF
authors.lastname: Yang
mesh_terms: D000095:Acetolactate Synthase / Q000037:antagonists & inhibitors*; D006540:Herbicides / Q000138:chemical synthesis / Q000737:chemistry*; D006801:Humans; D010793:Phthalazines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010944:Plants / Q000187:drug effects; D013329:Structure-Activity Relationship
chemical_list: D006540:Herbicides; D010793:Phthalazines; D000095:Acetolactate Synthase