QSAR and 3D-QSAR analysis of structurally diverse ALS inhibitors: sulfonylureas and triazolopyrimidine-2-sulfonamides

For the purpose of better understanding the molecular mechanism of action of sulfonylurea and sulfonamide herbicides, the quantitative relationship between their structure and herbicidal activity against rape, Brassica campestris L, was analysed using physicochemical parameters and regression analysis and comparative molecular field analysis (CoMFA). The results showed that the structure–activity relationships of the two sets of compounds were identical, which suggested that the two different sets of compounds affect a common region of the receptor site. The CoMFA results were consistent with those derived from traditional QSAR analysis. Combining the traditional QSAR analysis with the CoMFA results, we can conclude that the variations in the herbicidal activity of the two sets of ALS inhibitors were governed dominantly by the three-dimensional steric and electrostatic field parameters of molecules participating in the interaction with the receptor site and there is apparently an optimum electronic property (Σσ or pKa) for the molecules to fit the receptor. © 1999 Society of Chemical Industry     

新型吡唑双酰肼类化合物的合成及除草活性

为了寻找具有较高除草活性的农药先导化合物,将吡唑环与双酰肼结构进行拼接,设计合成了13个未见报道的含吡唑环的双酰肼类目标化合物6a~6m,其结构均通过核磁共振氢谱及高分辨质谱确认。培养皿法测定结果表明:在200 mg/L下,化合物N'-(2-(2,4-二氯苯氧基)乙酰基)-3-(二氟甲基)-1-甲基-1H-吡唑-4-甲酰肼(6i)对小麦Triticum aestivum、油菜Brassicacampestris、高粱Sorghum bicolor、萝卜Raphanus sativus和黄瓜Cucumis sativus根、茎的抑制率均达80%以上。盆栽试验表明:在有效成分150 g/hm2剂量下,采用苗后茎叶喷雾处理,化合物6i对反枝苋Amaranthus retroflexus和鳢肠Eclipta prostrata的抑制率均达80%;相同剂量下采用苗前土壤喷雾处理,6i对反枝苋A. retroflexus的抑制率也达80%。     

Pyrimidinyl-substituted amides and thioureas: syntheses, crystal structure and herbicidal activities

BACKGROUND: The high herbicidal activities of [1,2,4]triazolo[1,5-c]pyrimidine and 2H-1,2,4-thiadiazolo[2,3-a]pyrimidine derivatives suggested the development of new fused heterocyclic compounds for application as herbicides. RESULTS: Three series of pyrimidinyl-substituted thioureas (4) and amides (5, 6) were synthesized, and the typical crystal structure of a 2H-1,2,4-thiadiazolo[2,3-a]pyrimidine derivative (5a) was determined by X-ray diffraction. All the compounds were tested for herbicidal activity against selected weeds. CONCLUSION: The series of fused heterocyclic amides 5a to 5d exhibited high herbicidal activities both against monocotyledonous weeds (Echinochloa crus-galli L., Sorghum bicolor (L.) M?nch., Digitaria sanguinalis (L.) Scop) and against dicotyledonous weeds (Amaranthus retroflexus L. and Brassica campestris L.) in pre-emergence treatments. In particular, compound 5b at low concentration still showed high inhibitory activity against A. retroflexus in pre-emergence treatment. Different substituents at the meta positions of the pyrimidine ring were found to affect the herbicidal activity.     

含咪唑啉酮结构的吡唑类对羟基苯基丙酮酸双加氧酶抑制剂的除草活性及选择性研究

对羟基苯基丙酮酸双加氧酶（HPPD）是一种重要的除草剂作用靶标。为了发现具有高活性和高选择性的新型HPPD抑制型除草剂,对前期合成的23个含咪唑啉酮结构单元的吡唑类衍生物（2A~2W）进行了深入的生物活性评价和构效关系研究,比较了它们对拟南芥HPPD（AtHPPD）和人源HPPD（hHPPD）抑制活性的差异,从酶水平上总结了该类化合物的结构-活性关系和种属选择性规律,从活体植株水平研究了它们的除草活性。结果表明:部分化合物表现出良好的除草活性和作物安全性,其中化合物2E和2G在150 g/hm2剂量下对荠菜、繁缕、小藜和棒头草抑制活性达到80%以上,且其对作物的安全性也明显优于商品化除草剂硝磺草酮。此外,化合物2P在酶水平上的选择性倍数高达93倍,展示出良好的应用潜力。     

吡唑酰胺基脲类化合物的合成及除草活性

根据活性结构拼接原理,以1-甲基-3-乙基-5-吡唑甲酰肼为起始原料,设计合成了19个新吡唑酰胺基脲类衍生物,其结构均经过核磁共振氢谱、红外光谱、质谱和元素分析确证。生物活性测试结果表明:大部分化合物对双子叶杂草苘麻Abutilon theophrasti、反枝苋Amaranthus retroflexus以及凹头苋A.ascedense显示出较好的除草活性及选择性,如在2 250 g/hm2的剂量下,3i在苗后和苗前处理时,对苘麻和反枝苋的抑制率都达到了100%。复筛的结果表明,在375 g/hm2下,3i对双子叶杂草表现出中等除草活性。     

Evaluation of novel sulfonylurea derivatives with a fused heterocyclic moiety as paddy herbicides that control sulfonylurea‐resistant weeds

Herbicidal activity and acetolactate synthase (ALS) inhibition of sulfonylurea derivatives with a fused heterocyclic moiety bonded to a sulfonyl group were investigated. Some compounds that had an imidazo[1,2‐b]pyridazine moiety substituted at the 2‐position by chlorine or methyl controlled sulfonylurea‐resistant (SU‐R) weeds and showed inhibitory activity to ALS prepared from SU‐R Schoenoplectus juncoides shoot. There was a correlation between in vitro and whole‐plant herbicidal activity of the compounds mentioned above against SU‐R Schoenoplectus juncoides. Among them 1‐(2‐chloro‐6‐propylimidazo[1,2‐b]pyridazin‐3‐ylsulfonyl)‐3‐(4,6‐dimethoxypyrimidin‐2‐yl)urea, propyrisulfuron, was selected for further evaluation. Propyrisulfuron effectively controlled paddy weeds at doses of 70 and 140 g a.i. ha^?1 with good rice selectivity in a field trial.     

Synthesis, crystal structure, bioactivity and DFT calculation of new oxime ester derivatives containing cyclopropane moiety

A new series of oxime esters containing cyclopropane moiety were designed and synthesized. Their structures were confirmed by ¹H NMR, MS and elemental analysis. The single crystal structure of compound 7b was determined to further elucidate the structure. The KARI activity indicated that compound 7k exhibits favorable inhibition rate; the herbicidal assay showed that most of them have moderate activity against Echinochloafrumentacea, some of which have moderate activity against Brassica campestris.     

双环磺草酮除草活性及对水稻的安全性研究

双环磺草酮是一种以对-羟苯基丙酮酸双氧化酶 (HPPD) 为作用靶标的双环辛烷类化学除草剂。为明确其在水稻田的应用技术,采用温室盆栽法测定了双环磺草酮的杀草谱、除草活性及对8个水稻品种的安全性。结果表明:在有效成分360 g/hm2剂量处理下,双环磺草酮对水稻田常见杂草稗草Echinochloa crusgalli、雨久花Monochoria korsakowii、异型莎草Cyperus difformis的地上部分鲜重抑制率均高于90%,对主要秋熟杂草稗草E. crusgalli、牛筋草Eleusine indica、雨久花M. korsakowii、千金子Euphorbia lathyris、田皂角Aeschynomene indica和异型莎草C. difformis的GR₅₀值为有效成分48~196 g/hm2,除田皂角外,除草活性均高于对照药剂硝磺草酮。双环磺草酮对8个水稻品种的安全性研究结果表明:在有效成分720 g/hm2剂量处理下,隆两优华占、皖垦糯1号、皖稻68和绿旱粳1号4个水稻品种对双环磺草酮耐药性较高,徽两优882、C两优608、皖稻119和Y两优1号4个水稻品种的株高和鲜重受到不同程度的抑制。双环磺草酮在隆两优华占、皖垦糯1号、皖稻68和绿旱粳1号4种水稻与异型莎草、稗草和雨久花3种杂草之间的选择性指数分别为3.66~4.37、4.50~5.37、3.36~4.01和3.29~3.93,明显高于对照药剂硝磺草酮。研究表明,双环磺草酮对多种秋熟杂草防效较好,且对供试的3个粳稻品种及5个籼稻品种中的隆两优华占安全。     

Studies of the New Herbicide KIH-6127. Part III. Synthesis and Structure–Activity Studies of Analogues of KIH-6127 against Barnyard Grass (Echinochloa oryzicola)*

The previously evaluated prototype, methyl 6-acetyl-2-[(4,6-dimethoxypyrimidin-2-yl)oxy]benzoate, was modified by the introduction of an oximino group. Further extensive synthetic modifications were then made to the 6-alkyl moiety (R¹), the ester moiety (R²), the alkoxyimino moiety (R³), the bridge-atom (X) and the 4,6-disubstituted-pyrimidine moiety (A, B, Z). Structure–activity relationships of the synthesized compounds were studied by examining their herbicidal activity against Barnyard grass (Echinochloa oryzicola) in paddy rice at various growth stages, including pre-emergence. The novel herbicide methyl 2-[(4,6-dimethoxypyrimidin-2-yl)oxy]-6-[1-(methoxyimino)ethyl]benzoate, (KIH-6127) was found to be the most effective compound. The commercial development of this compound is currently in progress. © 1997 SCI.     

Use of mesotrione and tembotrione herbicides for post-emergence weed control in alkaloid poppy (Papaver somniferum)

Two field experiments were carried out a year apart on the alkaloid poppy (Papaver somniferum) in 2012 and 2013 in north-west Hungary, to assess the efficacy of mesotrione and tembotrione herbicides for post-emergence weed control. Our experiments tested (1) a single application of mesotrione at 144 g active ingredient (a.i.) ha^–1, (2) two separate applications of mesotrione at 144 g a.i. ha^–1, (3) a single application of tembotrione at 88 g a.i. ha^–1, (4) two separate applications of mesotrione at 88 g a.i. ha^–1, and (5) the combination of a single application of mesotrione at 144 g a.i. ha^–1 followed by a single application of tembotrione at 88 g a.i. ha^–1. Both non-treated and hand-weeded plots were used as controls. Among the most important weeds, Chenopodium album was most successfully controlled in the majority of the test treatments, but Fallopia convolvulus and Polygonum aviculare tolerated each herbicide application in 2012, likely due to the dry weather conditions. Because of the botanical similarity to the crop, none of the treatments proved to be significant against Papaver rhoeas. One dosage of tembotrione alone never reduced the dry weights of the target weed species or weed numbers significantly. The cuticular wax layer of the opium poppy can provide a natural defence against these herbicides, but some temporary phytotoxic yellowish discoloration occurred after tembotrione treatments. Our results show that mesotrione in combination with tembotrione is the most effective treatment and should be employed in poppy cultivation.     

(2E,4Z )-Decadienoic acid and (2E,4Z,7Z )-decatrienoic acid,two herbicidal metabolites from Streptomyces viridochromogenes Tü 6105

Two fatty acids, (2E,4Z)-decadienoic acid and (2E,4Z,7Z)-decatrienoic acid, the latter being described for the first time as a natural product, were detected in the culture filtrate of Streptomyces viridochromogenes Tü 6105 by HPLC-diode array screening, purified by chromatographic methods and structurally elucidated by NMR techniques. Both metabolites show strong herbicidal activity against Lemna minor and Lepidium sativum. The herbicidal activities of the isolated compounds were compared with those of similar fatty acids and derivatives. © 1999 Society of Chemical Industry     

Preparation of some novel phosphonamidates,their phytotoxicity and herbicidal properties

Fourteen new O-phenyl/4-chlorophenyl-N-alkyl/aryl-2-chloroethyl phosphonamidates have been prepared and screened for their phytotoxicity towards monocotyledonous (wheat) and dicotyledonous (mustard) plants and herbicidal activity against wild oat. O-Phenyl-N-propyl-2-chloroethyl phosphonamidate was found to be the most phytotoxic (pre-emergence) and also possessed herbicidal properties. Wheat showed maximum resistance to most of the compounds (post-emergence). N-propyl-4-chlorophenyl-2-chloroethyl phosphonamidate was the least active molecule. © 1998 SCI.     

含肟醚并取代异 NFDA1唑环的氨基甲酸酯类化合物的合成及生物活性

为寻找具有优异生物活性的氨基甲酸酯类化合物,根据活性亚结构拼接原理,将取代异 NFDA1 唑和肟醚基团引入多菌灵结构中,以取代苯甲醛 (1) 和2-氯苄胺(3) 为起始原料,经多步反应设计合成了10个未见文献报道的含肟醚并取代异 NFDA1 唑的氨基甲酸酯类化合物,其结构经 1H NMR 和 MS 确证。初步生物活性测定结果表明,部分目标化合物不仅具有一定的杀菌活性,同时还具有较好的除草活性。其中,活体盆栽试验结果表明,化合物11b对黄瓜霜霉病Pseudoperonospora cubensis 的相对防效为90%,对黄瓜白粉病Sphaerotheca fuliginea 的相对防效达95%,低于对照药剂多菌灵;除草活性皿测法表明,化合物11c和11j 200 mg/L下对靶标作物的根、茎抑制率均达80%以上,与对照药剂异丙酯草醚活性相当。盆栽法表明,150 g/hm2下,化合物11c和11j对繁缕Stellaria media苗前和苗后的抑制率均在70%以上,低于异丙酯草醚。此类化合物的构效关系有待进一步研究。     

Are herbicide‐resistant crops the answer to controlling Cuscuta?

BACKGROUND: Herbicide‐resistant crop technology could provide new management strategies for the control of parasitic plants. Three herbicide‐resistant oilseed rape (Brassica napus L.) genotypes were used to examine the response of attached Cuscuta campestris Yuncker to glyphosate, imazamox and glufosinate. Cuscata campestris was allowed to establish on all oilseed rape genotypes before herbicides were applied. RESULTS: Unattached seedlings of C. campestris, C. subinclusa Durand & Hilg. and C. gronovii Willd. were resistant to imazamox and glyphosate and sensitive to glufosinate, indicating that resistance initially discovered in C. campestris is universal to all Cuscuta species. Glufosinate applied to C. campestris attached to glufosinate‐resistant oilseed rape had little impact on the parasite, while imazamox completely inhibited C. campestris growth on the imidazolinone‐resistant host. The growth of C. campestris on glyphosate‐resistant host was initially inhibited by glyphosate, but the parasite recovered and resumed growth within 3–4 weeks. CONCLUSION: The ability of C. campestris to recover was related to the quality of interaction between the host and parasite and to the resistance mechanism of the host. The parasite was less likely to recover when it had low compatibility with the host, indicating that parasite‐resistant crops coupled with herbicide resistance could be highly effective in controlling Cuscuta. Published 2009 by John Wiley & Sons, Ltd.     

Synthesis and herbicidal activities of novel 3-(substituted benzyloxy or phenoxy)-6-methyl-4-(3-trifluoromethylphenyl)pyridazine derivatives

BACKGROUND: 4‐(3‐Trifluoromethylphenyl)pyridazine represents a new series of compounds with bleaching and herbicidal activities. RESULTS: A total of 43 novel 3‐(substituted benzyloxy or phenoxy)‐6‐methyl‐4‐(3‐trifluoromethylphenyl)pyridazine derivatives were synthesised, and their bleaching and herbicidal activities were evaluated through Spirodela polyrrhiza and greenhouse tests. Some compounds exhibited excellent herbicidal activities, even at a dose of 7.5 g ha^?1. CONCLUSION: The results showed that a substituted phenoxy group at the 3‐position of the pyridazine ring and the electron‐withdrawing group at the para ‐position on the benzene ring were essential for high herbicidal activity. Copyright © 2011 Society of Chemical Industry     

Design and synthesis of N-(2,4=difluorophenyl)-2-(3-trifluoromethylphenoxy)-3-pyridinecarboxamide (diflufenican), a novel pre- and early post-emergence herbicide for use in winter cereals

The pre- and early post-emergence herbicidal activity of diflufenican, a novel herbicide, is reported and attention is drawn to its ability to control important weeds in winter cereals, including Galium aparine, Veronica hederifolia, Veronica persica and Viola arvensis, which are resistant to substituted-urea herbicides. The synthesis of a series of related compounds is described and the relationship between structure and activities against a range of plant species is examined in respect of changes in the phenyl, phenoxy and pyridine rings. The design and synthesis of a small number of compounds combining the best patterns of substitution in each of the rings is described. The resulting optimisation of herbicidal activity in the series is reported, together with field trial results comparing the herbicidal efficacy, crop selectivity and soil persistence of the most active structures.     

Synthesis and characterisation of some 4‐keto derivatives of 1,3,4(2H)‐isoquinolinetrione redox mediator herbicides

Derivatives of 2‐ethyl‐1,3,4(2H)‐isoquinolinetrione in which the 4‐keto group has been modified to (Z)‐oxime, (E)‐ and (Z)‐O‐methyl oxime, (Z)‐N,N‐dimethyl hydrazone, cyano‐imine and dicyanomethylene moieties have been prepared and evaluated as redox mediator herbicides. All of the compounds have the free‐radical properties required to function as redox mediators, as determined by cyclic voltammetry, though only the O‐methyl oximes, the N,N‐dimethyl hydrazone and the cyano‐imine have reduction potentials in the range required to stimulate the light‐dependent consumption of oxygen at photosystem I in isolated chloroplasts. The O‐methyl oximes and the cyano‐imine are fast‐acting post‐emergence herbicides, producing symptoms of rapid desiccation; the (E)‐O‐methyl oxime is the most active herbicide, being somewhat more potent than the parent isoquinolinetrione. Hydrolysis studies indicate that it is unlikely that any compound generates the parent isoquinolinetrione in vivo. Attempts to explain differences between in vitro and in vivo activities using hydrolytic stabilities and physical properties were unsuccessful, and it was concluded that these factors probably play a less significant role in moderating the herbicidal activity of isoquinolinetrione derivatives than originally thought. © 2000 Society of Chemical Industry     

Novel 1,3,5-triazine derivatives with herbicidal activity

New fluoroalkyl-substituted 1,3,5-triazine derivatives were synthesized and screened for herbicidal activity using a greenhouse pot test. Surprisingly, a series of 2-alkyl-4-fluoroalkyl-6-aralkylamino-1,3,5-triazines e.g. 6-(4-bromobenzylamino)-2-methyl-4-trifluoromethyl-1,3,5-triazine was found to possess strong pre- and post-emergence herbicidal activities, although the conventional herbicidal 1,3,5-triazines generally should have a 2-substituted-4,6-diamino-1,3,5-triazine structure for herbicidal activity. Our compounds show strong Photosynthetic Electron Transport inhibitory activity (PI₅₀ c 7). Although their herbicidal effect is considered to be caused by a process similar to that for the conventional 1,3,5-triazine herbicide atrazine, they can control atrazine-resistant Chenopodium album effectively, and will thus form promising trial compounds for new triazine herbicide design.     

The herbicidal activity of 3-substituted 1-phenylureas

A variety of 1-phenylureas, substituted in the 3-position with one acyl, alkoxycarbonyl or cyano group, and optionally with a lower alkyl group, have been synthesised and assessed for pre- and post-emergence herbicidal activity against a range of monocotyledonous and dicotyledonous weed species. Generally, activity was associated only with compounds containing two small substituents in the 3-position. Their possible metabolic fate is discussed in the light of comparisons with the activity of the commercial herbicides, fenuron, monuron and diuron, and their de-methylated derivatives.     

环磺酮的除草活性及对玉米的安全性评价

为明确环磺酮在我国玉米田的应用技术和前景,采用温室盆栽法测定环磺酮的杀草谱和对常见杂草的除草活性以及对不同玉米品种的安全性,并通过田间药效试验验证其应用效果。结果表明,在100 g (a.i.)/hm²田间推荐剂量下进行茎叶处理时,环磺酮可以有效防除玉米田常见禾本科、莎草科和阔叶杂草,其中对反枝苋Amaranthus retroflexus、鳢肠Eclipta prostrata的活性较高,鲜重抑制率可达90%以上;对6种常见玉米田杂草稗Echinochloa crus-galli、马唐Digitaria sanguinalis、圆叶牵牛Ipomoea purpurea、反枝苋、碎米莎草Cyperus iria和青葙Celosia argentea的生长抑制中量GR₅₀分别为8.44、17.16、9.37、8.68、9.40和32.51 g (a.i.)/hm²,在供试剂量下环磺酮的除草活性均高于对照药剂硝磺草酮;田间推荐剂量下环磺酮对除黑糯301品种以外的11个玉米品种均较为安全,提高到2倍推荐剂量时,对不同玉米品种的生长抑制均增强;环磺酮对郑单958、珍珠糯8号、苏科甜1506和中糯2号4个玉米品种以及稗、马唐、圆叶牵牛、反枝苋、碎米莎草和青葙6种杂草之间均具有较好的选择性,选择性指数为10.40~29.14。田间药效试验表明,126 g (a.i.)/hm²环磺酮处理茎叶后第28天,对玉米田杂草稗、马唐、狗尾草Setaria viridis、香附子Cyperus rotundus、圆叶牵牛、空心莲子草Alternanthera philoxeroides的总株防效为86.51%,鲜重防效为87.81%,且对供试玉米品种彩甜糯102安全。