Characterization of new photosynthesis-inhibiting imidazolidine derivatives. 1. Interpretation of post-emergence herbicidal performance from photosynthesis-inhibiting activity and systemicity

An attempt was made to account for quantitatively measured herbicidal performance of foliage-applied 5-hydroxy-3-methyl-2–oxo-imidazolidine-1-carboxamide derivatives by their photosynthesis-inhibiting activity and systemicity. Photosynthesis-inhibiting activity was estimated from the increase of chlorophyll fluorescence intensity in Chlorella vulgaris Beijer cells measured by a microplate scanner, and systemicity was also evaluated by computer-aided chlorophyll fluorescence imaging. The highest herbicidal performance was recorded for N-cyclohexyl-5-hydroxy-3-methyl-2-oxo-imidazo～idine-l-carboxamide, a compound with the second strongest photosynthesis-inhibiting activity and intermediate systemicity. Though neither photosynthesis-inhibiting activity nor systemicity showed significant correlation with the actual herbicidal performance in simple regression analyses, a high predictability was found for a multiple regression on both parameters as two independent variables, suggesting that these two factors work cooperatively in the field performance.     

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.     

阿魏酸衍生物的合成及其除草活性测定

为从天然产物中获取新的除草活性成分,通过化学合成的方法对分离自瓜果腐霉Pythium aphanidermatum代谢产物中的阿魏酸进行了结构改造,并采用小杯法,以马唐、马齿苋和播娘蒿为供试杂草对所得化合物进行了除草活性测定。结果显示:所合成的4-羟基-3-甲氧基肉桂酸乙酯、4-羟基-3-甲氧基肉桂酸邻氯苯胺、4-羟基-3-甲氧基肉桂酸酰肼、4-羟基-3-甲氧基肉桂酸叔丁酯和4-乙酰氧基-3-甲氧基肉桂酸5种化合物的回收率分别为96.81%、97.39%、82.20%、75.67%和98.29%。4-羟基-3-甲氧基肉桂酸酰肼和4-乙酰氧基-3-甲氧基肉桂酸对马齿苋胚根的抑制活性最强,IC50分别为87.50 mg/L和74.86 mg/L,其余3种活性相对较弱;4-羟基-3-甲氧基肉桂酸乙酯和4-乙酰氧基-3-甲氧基肉桂酸分别在500 mg/L和1 000 mg/L浓度下可完全抑制播娘蒿和马齿苋胚根、芽的生长,而4-羟基-3-甲氧基肉桂酸邻氯苯胺则在1 000 mg/L浓度下可完全抑制播娘蒿胚根的生长。表明在阿魏酸分子中的不同位点引入适当的基团结构可以提高或者降低阿魏酸分子的除草活性,并获得新的除草活性物质。     

嘧啶联吡唑甲酰胺类化合物的合成及除草活性

设计合成了一系列结构新颖的嘧啶联吡唑甲酰胺类化合物5a~5o,其结构均经过1H NM R和MS分析确证。初步生物活性测试结果表明:在有效成分150 g/hm2剂量下苗后茎叶喷雾处理时,化合物(R)-N-[1-(4-氯苯基)乙基]-3-二氟甲基-1-(4,6-二甲氧基嘧啶-2-基)-1H-吡唑-4-甲酰胺(5c)、N-[1-(4-氯苯基)乙基]-1-(4,6-二甲氧基嘧啶-2-基)-N-甲基-3-三氟甲基-1H-吡唑-4-甲酰胺(5i)和N-[1-(4-氯苯基)乙基]-1-(4,6-二甲氧基嘧啶-2-基)-3-三氟甲基-1H-吡唑-4-甲酰胺(5k)对繁缕Stellaria media的抑制率高达90%以上;而同样剂量下苗前土壤喷雾处理时,化合物N-[1-(4-氯苯基)乙基]-3-二氟甲基-1-(4,6-二甲氧基嘧啶-2-基)-1H-吡唑-4-甲酰胺(5b)和5c对繁缕的抑制率达100%。该类结构化合物有望作为除草先导化合物进行开发。     

Pyrazole phenyl ether herbicides inhibit protoporphyrinogen oxidase

Two isomeric pairs of pyrazole phenyl ether herbicides [AH 2.429, 4-chloro-1-methyl-5-(4-nitrophenoxy)-3-(trifluoromethyl)-1H-pyrazole; AH 2.430, 4-chloro-1-methyl-3-(4-nitrophenoxy)-5-(trifluoromethyl)-1H-pyrazole; AH 2.431, 5-((4-chloro-1-methyl-5-(trifluoromethyl)-1H-pyrazol-3-yl)oxy)-2-nitrobenzoic acid; and AH 2.432, 5-((4-chloro-1-methyl-3-(trifluoromethyl)-1H-pyrazol-5-yl)oxy)-2-nitrobenzoic acid were evaluated for herbicidal activity in both intact plants and in tissue sections. Their capacity to induce accumulation of porphyrins in tissue sections and to inhibit protoporphyrinogen oxidase (Protox) in vitro were determined. In whole plant tests, the order of herbicidal activity was AH 2.430 AH 2.431 > AH 2.429 > AH 2.432. AH 2.430 consistently caused light-dependent membrane leakage in both green and far-red light grown cucumber cotyledon and barley primary leaf tissue sections after incubation for 20 hr in darkness in 0.1 mM solutions. The same treatment caused marked increases in protoporphyrin IX (PPIX) content during the 20-hr dark incubation. AH 2.429 and 2.431 were less effective and not effective in all tissues in causing herbicidal damage and PPIX accumulation. AH 2.432 was ineffective in tissue section assays. Mg-PPIX levels were not significantly affected by any of the compounds. Protochlorophyllide levels were decreased by AH 2.430 and 2.431 in barley and increased by AH 2.429, 2.431, and 2.432 in cucumber. A positive relationship was found between herbicidal activity and the amount of PPIX that was caused to accumulate by each compound. All of the compounds inhibited Protox activity. Positive correlations were found between herbicidal activity in planta over a 300-fold range and in vitro Protox inhibition and the amount of PPIX caused to accumulate in vivo. These data support the view that the pyrazole phenyl ethers exert their herbicidal activity entirely through inhibition of Protox.     

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%。     

Sorption–desorption of 'aged' isoxaflutole and diketonitrile degradate in soil

Isoxaflutole is a relatively new herbicide used for weed control in maize. The objective of this research was to increase the understanding of the behaviour and environmental fate of isoxaflutole and its diketonitrile (DKN) degradate in soil, including determination of the strength of sorption to soil and whether sorption is affected by ageing. In sandy loam (SL) and silty clay (SiCl) soils, ¹⁴C‐isoxaflutole was found to dissipate rapidly after application to soil; recovery ranged from ～42% to 68% at week 0, and recovery had decreased to <10% at week 12. Decreases in ¹⁴C isoxaflutole residues over time in SL and SiCl soils are consistent with hydrolysis of isoxaflutole and formation of bound DKN residues in the soil. DKN recovery from freshly treated SiCl and SL soils was 41% to 52%. After a 12‐week incubation in SL soil at pH 7.1 and 8.0, recoveries were similar, ～40%. However, at week 12 in SL soil pH 5.7, DKN recovery decreased to ～28%. DKN recovery in SiCl soil at week 12 was <10%. Increases in sorption of DKN in SL at pH 5.7 and SiCl soil over time indicate that the DKN degradate is tightly bound to the soil and sorption is affected by soil pH and soil type. Sorption of ¹⁴C‐DKN in the SiCl soil more than doubled with ageing compared with the lower K_d sorption coefficient values of the SL soils. In the SiCl soil at time 0, the K_d was 0.6; at 1 week, K_d increased to 2; and at the end of the 12‐week incubation period, K_d was 4.5. This strong binding of DKN to the soil may be due to chelate formation in the interlayer of the clay.     

Phytotoxicity of m-phenoxybenzamides: Inhibition of cell-free phytoene desaturation

Inhibition of carotenoid biosynthesis by herbicidal m-phenoxybenzamide derivatives has been investigated in a cell-free carotenogenic system from Aphanocapsa. Their target is the phytoenedesaturase reaction. Double-reciprocal plots of β-carotene biosynthesis (from ¹⁴C-labeled geranylgeranyl pyrophosphate) showed that 3-(2,5-dimethylphenoxy)-N-ethylbenzamide was a noncompetitive inhibitor of the phytoene-desaturase complex. The K_i value for cell-free inhibition of β-carotene formation was almost identical to the I₅₀ value of intact cells. Furthermore, the influence of certain substituents on herbicidal activity has been investigated. Inhibition increased with the length of the unbranched N-alkyl chains. In addition, substituents at the phenoxy group with higher lipophilicities showed greater inhibitory activities. The presence of a phenoxy or trifluoromethyl moiety at position 3 is essential.     

Effect of fungal metabolites and some derivatives against Tribolium castaneum (Herbst) and Nezara viridula (L.)

Two fungal metabolites, aspyrone (3-(1,2-epoxypropyl)-5-hydroxy-6-methyl-5,6-dihydropyran-2-one) and asperlactone (3-(1,2-epoxypropyl)-5-(1-hydroxyethyl)-5-furan-2-one) were isolated from an Aspergillus ochraceus Wilhelm strain showing IGR activity against Tribolium castaneum (Herbst). Synthetic derivatives of aspyrone were produced using published methods. These derivatives together with aspyrone and asperlactone were tested for insect growth-regulating activity against T. castaneum, and for ovicidal activity against Nezara viridula L. Of the compounds tested asperlactone appeared to be the most active.     

Characterization of triadimefon sorption in soils using supercritical fluid (SFE) and accelerated solvent (ASE) extraction techniques

Sorption–desorption of the fungicide triadimefon in field‐moist silt loam and sandy loam soils were determined using low‐density supercritical fluid extraction (SFE). The selectivity of SFE enables extraction of triadimefon from the soil water phase only, thus allowing calculation of sorption coefficients (K_d) at field‐moist or unsaturated conditions. Triadimefon sorption was influenced by factors such as soil moisture content and temperature; sorption increased with increased moisture content up to saturation, and decreased with increased temperature. For instance, K_d values for triadimefon on the silt loam and the sandy loam soils at 40 °C and 10% water content were 1.9 and 2.5 ml g⁻¹, respectively, and at 18% water content, 3.3 and 6.4 ml g⁻¹, respectively. Isosteric heats of sorption (ΔH_i) were −42 and −7 kJ mol⁻¹ for the silt loam and sandy loam soils, respectively. Sorption–desorption was also determined using an automated accelerated solvent extraction system (ASE), in which triadimefon was extracted from silt loam soil by 0.01 M CaCl₂. Using the ASE system, which is basically a fast alternative to the batch equilibration system, gave a similar ΔH_i value (−29 kJ mol⁻¹) for the silt loam soil (K_f = 27 µg^{1 − 1/n} ml^1/n g⁻¹). In order to predict transport of pesticides through the soil profile more accurately on the basis of these data, information is needed on sorption as a function of soil water content. © 2000 Society of Chemical Industry     

Sorption and dissipation of aged metolachlor residues in eroded and rehabilitated soils

BACKGROUND: Sorption and dissipation of aged metolachlor were characterized in rehabilitated and eroded prairie soils using sequential batch slurry (conventional) and accelerated solvent extraction (ASE). RESULTS: In spite of an almost twofold difference in soil organic carbon (OC) content, S‐metolachlor sorption coefficients (K_d) and dissipation rates (DT₅₀) were the same in soils from different landscape positions within an eroded landform. Soil was moved within the landform to increase productivity. In areas receiving topsoil addition, S‐metolachlor K_d was higher and DT₅₀ was longer than in eroded areas. The efficiency of extraction was higher for ASE than for conventional extractions. No consistent aging effect on K_d was observed. Mineralization in 8 weeks accounted for < 10% of the applied metolachlor. CONCLUSION: The results of this laboratory study support a field dissipation study. Both showed that S‐metolachlor has the same retention and dissipation rate throughout an eroded landform, which was not expected owing to the large variability in soil properties, including OC concentrations. Altering soil properties by adding topsoil increased metolachlor sorption and persistence. The method of extraction (conventional versus ASE) affected calculated sorption coefficients and dissipation rates. In all cases, groundwater ubiquity scores (GUSs) categorized metolachlor as having intermediate mobility. Published 2012 by John Wiley & Sons, Ltd.     

Quantitative structure—activity relationships of light-dependent herbicidal 4-pyridone-3-carboxanilides I. Effect of benzene ring substituents at the anilide moiety

A number of substituted 4-pyridone-3-carboxanilide derivatives show various degrees of light-dependent herbicidal activity. The effects of substituents at the anilide moiety on the activity against Echinochloa oryzicola were analysed quantitatively with physicochemical substituent parameters. The activity was shown to vary parabolically with total hydrophobicity (Σπ) of the anilide ring substituents as well as with the steric parameter (E_s) of the ortho-substituents. The E_s parameter for only the bulkier ortho-substituent, with the more negative value, but not for the two, was significant. The effect of substituents at the 1-position was expressible by indicator variables assigned to each 1-substituted series, the physicochemical rationalization being left for future analyses.     

Sorption of atrazine and dicamba in Delaware coastal plain soils: a comparison of soil thin layer and batch equilibrium results

The mobility and retention of atrazine and dicamba in six Atlantic Coastal Plain soils were estimated by soil thin-layer chromatography (soil-TLC). The soils studied were representative of the major agricultural regions in Delaware and were sampled, by horizon, to the water table. Four horizons from each profile were leached simultaneously with distilled water on one soil-TLC plate. Two values were obtained from each plate: the ratio of the distance traveled by the herbicide center of mass over that traveled by the solvent front (R_m), and a sorption distribution coefficient (K_d). The R_m values ranged from 0·06 to 0·94 for atrazine and from 0·80 to 0·94 for dicamba. Herbicide mobility was found to be greatest in coarse-textured soil horizons that contained low levels of organic matter, clay, and Fe and Al oxides. Correlation analysis indicated that effective cation exchange capacity, exchangeable acidity, exchangeable aluminum, and clay were useful predictive variables or both atrazine mobility and sorption. Organic matter was not useful for predicting soil-TLC derived sorption estimates; however, it was correlated to K_d-batch estimates. Distribution coefficients calculated from soil-TLC data were found to be in general agreement with K_d values obtained for the same soils by batch equilibrium techniques. The average K_d-soil-TLC values for atrazine and dicamba were 2·09(±2·24) and 0·03(±0·02), respectively. The ratio of the batch K_d to the soil-TLC K_d ranged from 0·1 to 19 (x̄=1·6, SD=3·8) for atrazine and from 2·9 to 38 (x̄=12·6, SD=8·7) for dicamba. Thus, although for some horizons agreement between the two methods was good, for other horizons significant discrepancies existed. It is suggested that the soil-TLC gives results under non-equilibrium conditions, whereas the batch procedure is, by definition, at quasi-equilibrium. These fundamental differences may account for the observed differences between the two methods. It is also suggested that, due to this difference, the soil-TLC procedure can provide additional information relevant to herbicide partitioning in the field environment that is not provided by traditional batch equilibrium techniques. © 1998 Society of Chemical Industry     

Sorption of lonisable organic compounds by field soils. Part 2: Cations,bases and zwitterions

Sorption of a range of permanent cations, bases and zwitterionic compounds was measured as a function of pH in two soil types. Pyridinium cations were more strongly sorbed (K_d 10– > 1000) than aliphatic cations (K_d < 5). At very low pH, sorption of the aliphatic cations sharply decreased, probably because they are displaced by protons. Most weak bases, including carbendazim andpyridines, were strongly sorbed (K_d 9–35) at low pH, where they would be appreciably protonated, sorption becoming much weaker at soil pH values > 6. However, an additional mechanism of sorption was observed for those zwitterions capable of chelation (e.g. picolinic acid and alanine) which gave rise to high K_d values at pH values near neutral. Inorganic phosphate was strongly sorbed (K_d > 140) save at very low pff. Glyphosate and inorganic phosphate were sorbed very strongly at pH values near to 4 (K_d > 200). The very strong sorption was attributed to ligand exchange interaction. Sorption of picolinic acid was similar when measured in water or calcium chloride solution (0.01 M). However, sorption decreased with increasing concentration of calcium chloride up to 1 M, probably because the protonated form of picolinic acid was displaced by calcium ions.     

4-羟基-3-甲氧基肉桂酸乙酯的生物活性及其除草作用机制

为明确以天然产物阿魏酸为母体进行化学结构改造得到的化合物4-羟基-3-甲氧基肉桂酸乙酯的生物活性及其除草机制,利用茎叶喷雾法和小杯法测定其对马唐和反枝苋的生物活性,基于生理生化指标及功能基因表达量对其除草作用机制进行研究。结果表明:4-羟基-3-甲氧基肉桂酸乙酯对马唐茎叶鲜重抑制中浓度IC50为46.27 mg/L;对反枝苋胚根和芽的IC50分别为129.94 mg/L和147.33 mg/L,且在500 mg/L浓度处理时可抑制反枝苋种子萌发;对拟南芥根长的IC50为43.82 mg/L,在160 mg/L浓度处理时拟南芥几乎停止生长、叶片发黄、根毛堆积。该化合物以1 000 mg/L浓度处理马唐叶片2、3、8 h后,电导率较对照组分别增加了22.70%、18.46%和25.62%;1 000 mg/L浓度处理下叶绿素a/b为2.43,较对照的3.62显著下降;处理后叶表微观结构观察发现化合物浓度越大,植物叶片表皮毛倒伏和褶皱越严重;拟南芥AT4G04820基因表达量显著下降,在处理45 min时下降最显著,与对照组相差42.52倍,微管蛋白含量下降,造成微管解离,从而抑制植物生长。表明4-羟基-3-甲氧基肉桂酸乙酯具有较强的除草活性,可能通过破坏细胞结构、抑制光合作用及阻止根生长等途径使杂草生长受到抑制甚至死亡。     

Bentazone Leaching in Spanish Soils

Adsorption, incubation and soil-column experiments with bentazone [3-isopropyl-1H-2,1,3-benzothiadiazin-4(3H)-one 2,2-dioxide] were carried out in ten different soils from the marches surrounding the Doñana National Park (Huelva, SW Spain). Adsorption isotherms for the different soils showed a good fit with the Freundlich equation. Bentazone was poorly adsorbed in all the soils studied, with no significant relationship between theK_f values and soil characteristics. A significant correlation was obtained between the soil organic matter content and the distribution constant values (K_d) calculated at an equilibrium concentration of 200 μg cm⁻³. The low adsorption and non-degradation of bentazone on these soils suggest that the herbicide readily percolates through soils to reach the surface and ground waters. The mobility of bentazone through three soil columns was also studied. The mass balances carried out showed that bentazone was totally eluted from the soil columns. The theoretical model applied to explain bentazone leaching under our experimental conditions seems to be suitable for soil columns with a uniform water-flow rate.     

新型含吡唑杂环邻氨基苯甲酰胺类化合物的合成与杀螨活性

以氯虫苯甲酰胺和氟虫腈的结构为基础,通过活性亚结构拼接的方法,设计合成了24个新型含吡唑杂环邻氨基苯甲酰胺类化合物,其结构经1H NM R、IR及APCI-M S表征。初步生物活性测试结果表明:化合物5-溴-N-[4-氯-2-甲基-6-(甲氨基甲酰基)苯基]-1-1-[2,6-二氯-4-(三氟甲基)苯基]-4-三氟甲基亚磺酰基-1H-吡唑-3-甲酰胺(5k)和5-溴-N-[4-溴-2-甲基-6-(甲氨基甲酰基)苯基]-1-[2,6-二氯-4-(三氟甲基)苯基]-4-三氟甲基亚磺酰基-1H-吡唑-3-甲酰胺(5l)在500 mg/L下对朱砂叶螨Tetranychus cinnabarinus的致死率为100%,但在100 mg/L下其致死率则分别降至30%和50%。所得结果可为邻氨基苯甲酰胺类化合物构效关系研究提供参考。     

Aryl N-hydroxy- and N-methoxy-N-methylcarbamates as potent reversible inhibitors of acetylcholinesterase

Several aryl N-hydroxy- and N-methoxy-N-methylcarbamates were examined as inhibitors of bovine erythrocyte acetylcholinesterase (AChE). These carbamate derivatives were generally strong inhibitors of AChE, but, unlike the typical N-methyl- and N,N-dimethylcarbamates which are carbamylating agents, they proved to be reversible, competitive inhibitors of the enzyme. The values for the dissociation constant (K_a) for the enzyme-inhibitor complex to enzyme and inhibitor were in the range of 2 × 10^?5?1 × 10^?7M.     

Differential Metal Binding Interactions of the Imidazolinones Revealed by NMR and UV Spectroscopy

NMR and UV spectroscopy and molecular modeling methods were applied to probe the interaction of the two imidazolinones, imazethapyr (5-ethyl-2-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)nicotinic acid) and its structural isomer CL 303,135 (5-ethyl-3-(4-isopropyl-4-methyl-5-oxo-2-imidazolin-2-yl)picolinic acid), with metal ions. Both the imidazolinones inhibit the enzyme acetohydroxyacid synthase (AHAS) in vitro. However, while imazethapyr is a herbicide that is used widely in agriculture, CL303,135 does not exhibit herbicidal activity. Imazethapyr and CL303,135 exhibited considerable differences in their interactions with metals. In the metal complex of imazethapyr, the carboxyl moiety binds strongly and the pyridine nitrogen binds weakly with metals. In the case of CL303,135, both the pyridine nitrogen and the carboxyl group that are positioned ortho to each other participated strongly in the binding and were found to act together as a strong bidentate ligand to a metal ion. Both of the imidazolinones form predominantly 2:1 complexes with multivalent metal ions. However, imazethapyr binds two orders-of-magnitude more weakly (1·0×10⁹ M ^-2) with metal ions compared to CL303,135 (1·7×10¹¹ M ^-2). The interactions of the model compounds, nicotinic acid and picolinic acid, with metals were examined similarly. It was concluded that the strong affinity of CL303,135 for metals compared to imazethapyr may affect its absorption from soil into plants, or its translocation in plants, thereby explaining the differences in herbicidal activity of imazethapyr and CL303,135. © 1997 SCI.     

Quantitative structure—activity relationships of light-dependent herbicidal 4-pyridone-3-carboxanilide derivatives II. Substituent effects of anilide and pyridone moieties

The variations in the light-dependent herbicidal activity against Echinochloa oryzicola of a number of 4-pyridone-3-carboxanilides with various substituents on the anilide and pyridone rings have been examined by use of physicochemical substituent parameters and regression analysis. The effects of substituents of the anilide ring were such that the activity was related parabolically not only with the substituent hydrophobicity (π) but also with the steric bulk parameter (E_s) of the bulkier ortho substituent. The effect of substituents at the 1-position of the pyridone ring was analysed with steric(STERIMOL L and B₅) and electronic(γ₁) parameters. That of substituents at the 5-position of the pyridone ring was explained by a parabolic function of a steric (MR) parameter. Analyses of the activity of 105 analogs confirmed that our previous selection of a candidate compound in this series for field trials was indeed appropriate in terms of physicochemical substituent effects.