Fahrenhorst-Jones Tyler, Lee Stephanie, Bollenbach-Wahl Birgit, Bojack Guido, Braun Ralf, Frackenpohl Jens, Heinemann Ines, Laber Bernd, Lange Gudrun, Peters Olaf, Reingruber Anna M, Schmutzler Dirk, Barber David M
Research and Development, Weed Control Research, Bayer AG, Crop Science Division, Industriepark Höchst, Frankfurt am Main, Germany.
Pest Manag Sci. 2025 May;81(5):2617-2634. doi: 10.1002/ps.8370. Epub 2024 Aug 19.
The sustainable control of weed populations is a significant challenge facing farmers around the world. Although various methods for the control of weeds exist, the use of small molecule herbicides remains the most effective and versatile approach. Striving to find novel herbicides that combat resistant weeds via the targeting of plant specific modes of action (MoAs), we further investigated the bicyclic class of acyl-acyl carrier protein (ACP) thioesterase (FAT) inhibitors in an effort to find safe and efficacious lead candidates.
Utilizing scaffold hopping and bioisosteric replacements strategies, we explored new bicyclic inhibitors of FAT. Amongst the investigated compounds we identified new structural motifs that showed promising target affinity coupled with good in vivo efficacy against commercially important weed species. We further studied the structure-activity relationship (SAR) of the novel dihydropyranopyridine structural class which showed promise as a new type of FAT inhibiting herbicides.
The current work presents how scaffold hopping approaches can be implemented to successfully find novel and efficacious herbicidal structures that can be further optimized for potential use in sustainable agricultural practices. The identified dihydropyranopyridine bicyclic class of herbicides were demonstrated to have in vitro inhibitory activity against the plant specific MoA FAT as well as showing promising control of a variety of weed species, particularly grass weeds in greenhouse trials on levels competitive with commercial standards. © 2024 The Author(s). Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.
杂草种群的可持续控制是全球农民面临的重大挑战。尽管存在多种杂草控制方法，但使用小分子除草剂仍然是最有效且用途广泛的方法。为努力寻找通过靶向植物特定作用模式（MoA）来对抗抗性杂草的新型除草剂，我们进一步研究了双环类酰基 - 酰基载体蛋白（ACP）硫酯酶（FAT）抑制剂，以寻找安全有效的先导化合物。
利用骨架跃迁和生物电子等排体替代策略，我们探索了FAT的新型双环抑制剂。在所研究的化合物中，我们鉴定出了新的结构基序，这些基序显示出有前景的靶标亲和力，并对具有商业重要性的杂草物种具有良好的体内活性。我们进一步研究了新型二氢吡喃吡啶结构类别的构效关系（SAR），该类别有望成为新型FAT抑制除草剂。
当前工作展示了如何实施骨架跃迁方法来成功找到新型且有效的除草结构，这些结构可进一步优化以用于可持续农业实践。已证明所鉴定的二氢吡喃吡啶双环类除草剂对植物特定作用模式的FAT具有体外抑制活性，并且在温室试验中对多种杂草物种，特别是禾本科杂草，显示出有前景的防除效果，其水平与商业标准相当。© 2024作者。由John Wiley & Sons Ltd代表化学工业协会出版的《害虫管理科学》。
