Key Laboratory of Pesticide & Chemical Biology, Ministry of Education, College of Chemistry, Central China Normal University, Wuhan 430079, PR China.
Bioorg Med Chem. 2010 Jul 15;18(14):4897-904. doi: 10.1016/j.bmc.2010.06.015. Epub 2010 Jun 11.
The triazolopyrimidine-2-sulfonanilide, discovered from preparing bioisosteres of the sulfonylurea herbicides, is an important class of acetohydroxyacid synthase (AHAS, EC 4.1.3.18) inhibitors. At least over ten triazolopyrimidine sulfonanilides have been commercialized as herbicides for the control of broadleaf weeds and grass with cereal crop selectivity. Herein, a series of triazolopyrimidine-2-sulfonanilides were designed and synthesized with the aim of discovery of new herbicides with higher activity. The assay results of the inhibition activity of the synthesized compounds against Arabidopsis thatiana AHAS indicated that some compounds showed a little higher activity against flumetsulam (FS), the first commercial triazolopyrimidine-2-sulfonanilide-type herbicide. The ki values of two promising compounds 3d and 8h are respectively, 1.61 and 1.29 microM, while that of FS is 1.85 microM. Computational simulation results indicated the ester group of compound 3d formed hydrogen bonds with the surrounding residues Arg'198 and Ser653, which accounts for its 11.5-folds higher AHAS inhibition activity than Y6610. Further green house assay showed that compound 3d has comparable herbicidal activity as FS. Even at the concentration of 37.5g.ai/ha, 3d showed excellent herbicidal activity against Galium aparine, Cerastium arvense, Chenopodium album, Amaranthus retroflexus, and Rmumex acetasa, moderate herbicidal activity against Polygonum humifusum, Cyperus iria, and Eclipta prostrate. The combination of in vitro and in vivo assay indicated that 3d could be regarded as a new potential acetohydroxyacid synthase-inhibiting herbicide candidate for further study.
三唑并嘧啶-2-磺酰苯胺类化合物是从磺酰脲类除草剂的生物等排体中发现的，是乙酰羟酸合成酶（AHAS，EC 4.1.3.18）抑制剂的重要类别。至少有十几种三唑并嘧啶磺酰苯胺类化合物已被商业化用作具有谷物选择性的阔叶杂草和禾本科杂草的除草剂。在此，设计并合成了一系列三唑并嘧啶-2-磺酰苯胺类化合物，旨在发现具有更高活性的新型除草剂。合成化合物对拟南芥 AHAS 的抑制活性测定结果表明，一些化合物对氟噻草胺（FS）表现出稍高的活性，FS 是第一个商业化的三唑并嘧啶-2-磺酰苯胺类除草剂。两个有前途的化合物 3d 和 8h 的 Ki 值分别为 1.61 和 1.29μM，而 FS 的 Ki 值为 1.85μM。计算模拟结果表明，化合物 3d 的酯基与周围残基 Arg'198 和 Ser653 形成氢键，这使其对 AHAS 的抑制活性比 Y6610 高 11.5 倍。进一步的温室试验表明，化合物 3d 与 FS 具有相当的除草活性。即使在 37.5g.ai/ha 的浓度下，3d 对繁缕、播娘蒿、藜、反枝苋和酸模叶蓼表现出极好的除草活性，对问荆、香附子和鳢肠表现出中等除草活性。体外和体内试验的组合表明，3d 可以被视为一种新的潜在的乙酰羟酸合成酶抑制剂除草剂候选物，用于进一步研究。
