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Cercosporin-Photocatalyzed [4+1]- and [4+2]-Annulations of Azoalkenes Under Mild Conditions
Published on: July 17, 2020
Design of N-Phenyltriazinone Derivatives with Ether-Linked Oxadiazole Moieties as Protoporphyrinogen IX Oxidase
Huang-Ze Yang1, Zi-Hao Huang1, Jin-Tong Zhang1
1National Pesticide Engineering Research Center, Frontiers Science Center for New Organic Matter, State Key Laboratory of Elemento-Organic Chemistry, College of Chemistry, Nankai University, Tianjin 300071, P.R. China.
Abstract:
Protoporphyrinogen IX oxidase (PPO, EC 1.3.3.4) has long been recognized as a validated target in herbicide development. In this research, through structural analysis, we devised an Active Fragment Exchange and Link (AFEL) methodology to engineer a new category of N-phenyltriazinone derivatives. These compounds feature ether-connected oxadiazole moieties and serve as potent inhibitors of Nicotiana tabacum PPO (NtPPO). Following systematic structure-activity relationship (SAR) optimization, 34 novel compounds were identified. These compounds exhibit nanomolar Ki values against NtPPO and show promising herbicidal activity, with some compounds demonstrating lower Ki values compared to saflufenacil. Greenhouse herbicidal activity assays revealed that compound Iq exhibited the highest efficacy, achieving 100% inhibition against tested broadleaf weeds at 37.5 g a.i./ha, comparable to saflufenacil. Compound Iq exhibited better crop safety for maize at 150 g a.i./ha relative to saflufenacil. Molecular docking simulations revealed that the oxadiazole ring in compound Iq forms two hydrogen bonds with the Arg98 residue of NtPPO. These findings suggest that compound Iq has the potential to be a novel PPO inhibitor for managing agricultural weeds.
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