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Discovery of Novel N‑Isoxazolinyl­phenyl­triazinones as Promising Protoporphyrinogen IX Oxidase Inhibitors

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journal contribution
posted on 31.10.2019, 11:06 by Da-Wei Wang, Rui-Bo Zhang, Shu-Yi Yu, Lu Liang, Ismail Ismail, Yong-Hong Li, Han Xu, Xin Wen, Zhen Xi
Protoporphyrinogen oxidase (PPO, EC is a promising target for herbicide discovery. Search for new compounds with novel chemotypes is a key objective for agrochemists. Here, we describe the discovery and systematic SAR-based structure optimization of novel N-isoxazolinyl­phenyl­triazinones 59 as PPO inhibitors. The in vivo herbicidal activity and in vitro Nicotiana tabacum PPO (NtPPO) inhibitory activity were explored in detail. A number of the new synthetic compounds displayed strong PPO inhibitory activity with Ki values in the nanomolar range. Some compounds exhibited excellent and broad-spectrum weed control at the rate of 9.375–37.5 g ai/ha by postemergence application and showed improved mono­cotyledonous weed control compared to saflufenacil. Most promisingly, ethyl 3-(2-chloro-5-(3,5-dimethyl-2,6-dioxo-4-thioxo-1,3,5-triazinan-1-yl)-4-fluorophenyl)-5-methyl-4,5-dihydroisoxazole-5-carboxylate, 5a, with a Ki value of 4.9 nM, displayed over 2- and 6-fold higher potency than saflufenacil (Ki = 10 nM) and trifludimoxazin (Ki = 31 nM), respectively. Moreover, 5a showed excellent and broad-spectrum weed control against 32 kinds of weeds at 37.5–75 g ai/ha. Rice exhibited relative tolerance to 5a at 150 g ai/ha by postemergence application, indicating that 5a could be a potential herbicide candidate for weed control in paddy fields.