Synthesis and Herbicidal Activity of &lt;i&gt;N&lt;/i&gt;-Alkyl-&lt;i&gt;N&lt;/i&gt;-(substituted benzyl)-4-halo-2-alkenamides

Matsunari, Kenji; Sugiyama, Hidetoshi; Sadohara, Hideo; Motojima, Kenji

doi:10.1584/jpestics.24.1

Cited by 7 publications

(5 citation statements)

References 2 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The predictive ability of the Agresense arti cial intelligence algorithm system for rational identi cation of the mechanism of action of novel molecules was con rmed post facto following extensive literature searches that identi ed earlier papers describing the herbicidal activity of related alkenamide compounds. 20,21 The activity of these compounds was light-dependent and was later on associated with inhibition of PPO. 22,23 Docking study Docking studies were performed to further understand the interaction between AGR001 and AGR002 with the catalytic domain of PPO.…”

Section: Discovery Of Novel Structuresmentioning

confidence: 99%

Novel Artificial Intelligence platform leads to the discovery of new protoporphyrinogen oxidase inhibitors

Barker

Geva²,

Simonovsky³

et al. 2022

Preprint

View full text Add to dashboard Cite

Weed control is essential in modern agriculture, though it has become more difficult with the emergence of resistance to most current herbicides and a slow registration process of new compounds. A new approach to identify possible herbicide candidates using an artificial intelligence algorithm that takes into effect biological parameters with the goal of reducing R&D time on new herbicides. Herein we describe the discovery of 4-chloro-2-pentenamides as novel inhibitors of protoporphyrinogen oxidase, a known herbicide target site, by the Agrematch AI. The herbicidal activity is confirmed in greenhouse assays, with the highest performing AGR001 showing good activity pre-emergent at 150 g/ha and post emergent as low as 50 g/ha on the troublesome weed palmer amaranth (Amaranthus palmeri). A lack of activity is reported on PPO resistant palmer amaranth carrying the glycine 210 deletion (ΔG210) mutation. The mechanism of action is confirmed by the herbicide-dependent accumulation of protoporphyrin IX, subsequent light-dependent loss of membrane integrity, and direct in vitro inhibition of protoporphyrinogen oxidase. Modeling of the docking of these inhibitors in the active site of protoporphyrinogen oxidase illustrates that their flexible side chains can accommodate a number of poses in the catalytic domain.

show abstract

Section: Discovery Of Novel Structuresmentioning

confidence: 99%

Novel Artificial Intelligence platform leads to the discovery of new protoporphyrinogen oxidase inhibitors

Barker

Geva²,

Simonovsky³

et al. 2022

Preprint

View full text Add to dashboard Cite

show abstract

“…the Amide Nitrogen Atom For compounds (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19) in Table 1 where the X substituent is fixed as 4-Cl, the activity varied considerably with variations in the structure of the R substituent. The activity was highest when R is n-Pr (in 3), i-Bu (in 6), and c-Pent (in 10), but very low when R is lengthy in such substituents as n-Oct (in 13) and multiply branched in such substituents as t-Bu (in 18) and t-Pent (in 19).…”

Section: Effects Of the Aliphatic Substituent (R) Attached Tomentioning

confidence: 99%

Quantitative Structure-Activity Relationships of Herbicidal N-Alkyl-N-(4-substituted benzyl)-4-chloro-2-pentenamides against Echinochloa oryzicola

et al. 1999

Self Cite

View full text Add to dashboard Cite

The herbicidal activity of N-alkyl-N-(4-substituted benzyl)-4-chloro-2-pentenamides against a barnyard grass species, Echinochloa oryzicola, was evaluated, and the potency variations were quantitatively analyzed using physicochemical parameters for the N-alkyl and the benzyl-benzene ring substituents in the amide moiety. The results indicated that the herbicidal potency was parabolically related with the total hydrophobicity of the amide moiety. The electron-withdrawing property of the benzene-ring substituents as well as their hydrogen-bonding accepting ability was significant in potentiating the herbicidal activity.

show abstract

“…Another lead herbicide adopted for this design is N -isobutyl- N -(4-chloro-benzyl)-4-chloro-2-pentenamide, which is a light-dependent amide herbicide reported by Kumai Chemical Co. Ltd. It can effectively control barnyard grass, throughout inhibiting cell division . According to its structure, carbonyl benzylamine is considered to be more important than the flexible side chain.…”

Section: Introductionmentioning

confidence: 99%

“…It can effectively control barnyard grass, throughout inhibiting cell division. 18 According to its structure, carbonyl benzylamine is considered to be more important than the flexible side chain. Therefore, this moiety was assumed as a pharmacophore for this lead herbicide.…”

Section: ■ Introductionmentioning

confidence: 99%

Design, Synthesis, and Herbicidal Activity of N-Benzyl-5-cyclopropyl-isoxazole-4-carboxamides

Sun

Sang

2020

J. Agric. Food Chem.

View full text Add to dashboard Cite

Based on the structures of isoxaflutole (IFT) and N-isobutyl-N-(4-chloro-benzyl)-4-chloro-2-pentenamide, a series of N-benzyl-5-cyclopropyl-isoxazole-4-carboxamides was designed by connecting their pharmacophores (i.e., a multitarget drug design strategy). A total of 27 N-benzyl-5-cyclopropyl-isoxazole-4-carboxamides were prepared from 5-cyclopropylisoxazole-4-carboxylic acid and substituted benzylamines, and their structures were confirmed by NMR and MS. Laboratory bioassays indicated that I-26 showed 100% inhibition against Portulaca oleracea and Abutilon theophrasti at a concentration of 10 mg/L, better than the positive control butachlor (50% inhibition for both weeds). A strong growth inhibition was observed, but a typical bleaching phenomenon of IFT could not be observed in the Petri dish assay. I-05 displayed excellent postemergence herbicidal activity against Echinochloa crusgalli and A. theophrasti at a rate of 150 g/ha, and bleaching symptoms were observed in the leaves of treated weeds. The bleaching effect of Chlamydomonas reinhardtii treated by I-05 could be reversed by adding homogentisate. Enzymatic bioassays indicated that I-05 could not inhibit 4-hydroxyphenylpyruvate dioxygenase (HPPD) activity, but II-05, an isoxazole ring-opening product of I-05, could inhibit HPPD activity with an EC50 value of 1.05 μM, similar to that of mesotrione (with an EC50 value of 1.35 μM). Detailed discussion about observed herbicidal symptoms is provided in the Results and Discussion section. This investigation provided a proof-of-concept foundation that a multitarget drug design strategy could be applied in agrochemical research.

show abstract

Synthesis and Herbicidal Activity of <i>N</i>-Alkyl-<i>N</i>-(substituted benzyl)-4-halo-2-alkenamides

Cited by 7 publications

References 2 publications

Novel Artificial Intelligence platform leads to the discovery of new protoporphyrinogen oxidase inhibitors

Novel Artificial Intelligence platform leads to the discovery of new protoporphyrinogen oxidase inhibitors

Quantitative Structure-Activity Relationships of Herbicidal <i>N</i>-Alkyl-<i>N</i>-(4-substituted benzyl)-4-chloro-2-pentenamides against <i>Echinochloa oryzicola</i>

Design, Synthesis, and Herbicidal Activity of N-Benzyl-5-cyclopropyl-isoxazole-4-carboxamides

Contact Info

Product

Resources

About