Quantitative structure–activity studies of insect growth regulators: XVI. Substituent effects of dibenzoylhydrazines on the insecticidal activity to Colorado potato beetle Leptinotarsa decemlineata

Insecticidal activity against the Colorado potato beetle, Leptinotarsa decemlineata, was measured for a series of substituted N-tert-butyl-dibenzoylhydrazines, in which one of the benzoyl moieties closer to the tert-butyl group was fixed as being 2-chloro-substitued and the other variously substituted singly or doubly. The effects of substituents on the activity were quantitatively analysed using the classical quantitative structure–activity relationship (QSAR) procedure. The activity against the Colorado potato beetle increases with the molecular hydrophobicity. In addition, various types of steric effect are at work, depending upon the positions. Hydrogen-bonding acceptor substituents at the para position enhance the activity. There seem to be threshold (or optimum) values, albeit position-dependent, in the molecular hydrophobicity, above which the activity starts to decrease. This biphasic contribution of the molecular hydrophobicity to activity against coleopterous larvae is the most conspicuous difference in substituent effects from those found for similar compounds against lepidopterous pest insects, and may be the basis of the variations in the activity spectrum for certain compounds in this series. The introduction of bulkier substituents into the meta- and para-positions of the benzene ring, apart from the tert-butyl group, is unfavorable to activity. LD₅₀ values against Colorado potato beetle larvae of methoxyfenozide (RH-2485) and tebufenozide (RH-5992) were in the order of 10⁻⁷ mol per insect, whereas those of RH-5849, and halofenozide (RH-0345) were very low, 10⁻⁹–10⁻¹⁰ mol per insect being selective to the coleopterous larvae. © 1999 Society of Chemical Industry     

2-取代苯并咪唑类化合物的合成及其抑菌活性

以甲基酮、草酸二乙酯或草酸二甲酯、盐酸羟胺和水合肼为原料,通过缩合、环合、水解等反应,将取代吡唑环、异 NFDA1 唑环引入苯并咪唑的2位,设计合成了13个未见文献报道的2-取代苯并咪唑类衍生物,其结构经红外、电喷雾串联质谱(ESI-MS)和核磁共振氢谱确证。初步生物活性测试结果表明,在100 mg/L质量浓度下,所有目标化合物对6种供试病原菌均具有一定的抑菌活性,其中2-吡唑取代的化合物 2a~2d 对苹果炭疽病菌Glomerella cingulata的抑制率在80%以上,2-异 NFDA1 唑取代的化合物 4a 对番茄早疫病菌 Alternaria solani 、苹果炭疽病菌和水稻稻瘟病菌 Magnaport hegrisease 的抑制率达100%。     

Synthesis and fungicidal activity of 1,4-dithiino[2,3-b]quinoxaline-2,3-dicarbonitriles

A series of eleven 1,4-dithiino[2,3-b]quinoxaline-2,3-dicarbonitriles was prepared by reaction of 2,3-dichloroquinoxalines with disodium (2)-2,3-dimercapto-2-butenedinitrile in N,N-dimethylformamide. These products were tested for in-vitro fungicidal activity by a Minimum Inhibitory Concentration (MIC) method. Several of these compounds showed broad-spectrum fungicidal activity. The activity exhibited by these compounds was greatly dependent upon the substituents of the quinoxaline ring, with the nitro-substituted derivatives showing the highest levels of antifungal activity. None of the compounds prepared, however, showed fungicidal activity comparable to that of the commercial fungicides screened.     

Synthesis and insecticidal activity of novel 1,3,4-oxadiazolin-5-one and pyrazolin-5-one derivatives

A series of novel 2-(2,4,6-trisubstituted phenyl)-1,3,4-oxadiazolin-5-one derivatives and 3-(2,4,6-trichlorophenyl)pyrazolin-5-one derivatives were synthesized and evaluated for insecticidal activity. It was found that a moderately bulky alkyl group, such as a tert-butyl group, on the heterocyclic ring, and a trifluoromethyl group on the benzene ring were optimal substituents on the molecule. The oxygen atom in the oxadiazoline ring was essential for insecticidal activity. Of the compounds assayed, 4-tert-butyl-2-(2,6-dichloro-4-trifluoromethylphenyl)-1,3,4-oxadiazolin-5-one gave the highest activity against Nephtotettix cincticeps, with an LC₅₀ value of 0.51 mg litre⁻¹. © 1999 Society of Chemical Industry     

Insect growth inhibition,antifeedant and antifungal activity of compounds isolated/derived from Zingiber officinale Roscoe (ginger) rhizomes

Fresh rhizomes of Zingiber officinale (ginger), when subjected to steam distillation, yielded ginger oil in which curcumene was found to be the major constituent. The thermally labile zingiberene‐rich fraction was obtained from its diethyl ether extract. Column chromatography of ginger oleoresin furnished a fraction from which [6]‐gingerol was obtained by preparative TLC. Naturally occurring [6]‐dehydroshogaol was synthesised following condensation of dehydrozingerone with hexanal, whereas zingerone and 3‐hydroxy‐1‐(4‐hydroxy‐3‐methoxyphenyl)butane were obtained by hydrogenation of dehydrozingerone with 10% Pd/C. The structures of the compounds were established by ¹H NMR, ¹³C NMR and mass (EI‐MS and ES‐MS) spectral analysis. The test compounds exhibited moderate insect growth regulatory (IGR) and antifeedant activity against Spilosoma obliqua, and significant antifungal activity against Rhizoctonia solani. Among the various compounds, [6]‐dehydroshogaol exhibited maximum IGR activity (EC₅₀ 3.55 mg ml ^?1) while dehydrozingerone imparted maximum antifungal activity (EC₅₀ 86.49 mg litre^?1). © 2001 Society of Chemical Industry     

靶向乙酰胆碱酯酶和几丁质合成酶杀虫剂衍生化合物三维定量构效关系模型构建

为获得活性更佳且同时具备苯甲酰基脲类和氨基甲酸酯类活性的新型双靶标杀虫剂——N-氯磺基-N-甲基氨基甲酸酯衍生物,构建此类化合物的三维定量构效关系（three-dimensional quantitative structure-activity relationship,3D-QSAR）模型,以18种具有双靶标活性的N-氯磺基-N-甲基氨基甲酸酯衍生物为训练集,分别采用比较分子力场分析（comparative molecular field analysis,CoMFA）法和比较分子相似性指数分析（comparative molecular similarity index analysis,CoMSIA）法进行3D-QSAR模型的构建,基于3D-QSAR模型分析同一骨架取代基的变化带给化合物的活性变化,预测不同力场对化合物活性的影响,并对设计的衍生化合物进行活性预测分析。结果表明,经CoMFA法和CoMSIA法构建的3D-QSAR模型可信度高（交叉验证系数q²分别为0.728和0.563）,且有良好的活性预测能力（非交叉验证系数r²分别为0.954和0.981）。基于该模型得到的化合物预测活性与实际活性残差较小且存在良好的线性关系,进一步证明所得3D-QSAR模型的可靠性。通过分析3D-QSAR模型的力场分布,推测在R¹基团处引入位阻较大的疏水性基团、在R²基团苯环的邻位引入同时具有负电性和疏水性但不含卤素原子的基团、用负电性的大位阻基团取代R基团等均可提高N-氯磺基-N-甲基氨基甲酸酯的活性。基于此设计的20种衍生化合物的活性变化从正反两方面印证了该推测的合理性。研究成果可用于指导兼具苯甲酰基脲类和氨基甲酸酯类杀虫剂作用机制的N-氯磺基-N-甲基氨基甲酸酯衍生物的设计。     

Quantitative structure-activity study of insecticidal 2-methoxy-5-(substituted-phenyl)-1, 3, 2-oxazaphospholidine 2-sulfides against Musca domestica L. by topical application

The quantitative relationship between the structure of 2-methoxy-5-(substituted-phenyl)-1, 3, 2-oxazaphospholidine 2-sulfides (5-PMOS) and their insecticidal activity against the house fly. Musca domestica L., was analyzed using reported physicochemical parameters and regression analysis. The electronic nature of the substituent on the phenyl group of 5-PMOS has the most significant effect on the activity, followed by hydrophobic and steric effects; the optimum value of Σρ is zero and the more hydrophobic the substituents on the phenyl group, the higher the insecticidal activity. The plots of observed pLD₅₀, values against calculated pLD₅₀ values for compounds having substituents in the ortho-position deviated downwards from those of compounds having substituents at the meta and/or para positions. This ortho-effect, which reduces the insecticidal activity of compounds having substituents at the ortho-position, was expressed by a dummy parameter D, which has the value 2 for di-ortho-substituted derivatives, 1 for mono-ortho-substituted derivatives and zero for others. Thus, the highest activity was obtained for 2-methoxy-5-phenyl-1, 3, 2-oxazaphospholidine 2-sulfide, and the activity was decreased by the introduction of any substituents on the phenyl group.     

Allylamine antimycotics: Recent trends in structure—activity relationships and syntheses

Methods developed for the synthesis of terbinafine-related allylamine antimycotics are reviewed. The synthesis of the en-yne side chains were generally accomplished by means of organometallic reactions. The use of Pd⁰-catalysed coupling reactions allowed easy access to derivatives bearing sensitive side-chain substituents. As examples, four metabolites of terbinafine were prepared via this procedure. Investigations with the carbon analogue of terbinafine revealed that, within the allylamine antimycotics, the nitrogen appears to be necessary for penetration by the drug into the fungal cell. Replacement of the naphthalene moiety of terbinafine by optionally substituted benzo[b]thiophenes led to a number of derivatives with high antifungal activity. A series of benzo[b]thienyl compounds with the side chain at position 7 and different substituents at position 3 showed significantly increased activity against Candida albicans in vitro. In particular, the 3-chloro derivative with the allylamine side chain at position 7(SDZ 87–469) proved to be the most potent allylamine antimycotic reported to this date. Two novel types of lead structures, the homopropargylamines and the benzylamines show very high activity in vitro.     

Synthesis and insecticidal/acaricidal activity of novel 3‐(2,4,6‐trisubstituted phenyl)uracil derivatives

A series of novel 3‐(2,4,6‐trisubstituted phenyl)uracil derivatives has been synthesised and assayed for insecticidal/acaricidal activity. The assay indicated certain requirements for optimal insecticidal activity, which can be summarised as follows: (a) the substituents on the phenyl ring should possess hydrophobicity and electron‐withdrawing properties, and the sum of their volumes determines the level of activity; (b) the substituent at the 6‐position on the uracil ring should also possess electron‐withdrawing properties and hydrophobicity, together with the correct volume; (c) the 1‐position on the uracil ring should be unsubstituted for activity against Nephotettix cincticeps and Epilachna vigintioctopunctata, but substituents with length C3 to C4 may be optimal for activity against Tetranychus urticae; (d) certain substituents at the 5‐position of the uracil ring give activity against E vigintioctopunctata and T urticae, but not against N cincticeps; (e) a thiocarbonyl group at the 2‐position of the uracil ring is less effective than a carbonyl group. Of the compounds assayed, 3‐(2,6‐dichloro‐4‐trifluoromethylphenyl)‐6‐trifluoromethyluracil showed high activity against all the species assayed. © 2000 Society of Chemical Industry     

Synthesis of some acetylenic and halovinyl heterocyclic carbonyl compounds and their activity against some phytopathogenic fungi

Twenty-three acetylenic or halovinyl carbonyl compounds with heterocyclic substituents were synthesised and tested in vivo against eight phytopathogenic fungi of different taxonomic classes. Some of them were fungicidal against Uromyces appendiculatus on Phaseolus vulgaris, though none showed a wide spectrum of activity.     

Structural Effects of N-Arylcarbamoylpyrazolines on Calcium Uptake in Rat Brain Synaptosomes

N-Arylcarbamoylpyrazolines with various substituents at the para position of the carbamoyl benzene ring inhibited ATP-dependent Ca²⁺-uptake in synaptosomes prepared from the rat brain. The activity of these compounds was evaluated as log(1/I₅₀), the reciprocal logarithm of half inhibitory concentration, I₅₀ (m ), from the concentration–response curve for the inhibition of Ca²⁺-uptake. Among the compounds tested, methyl 3-(4-chlorophenyl)-4-methyl-1-[N-(4-trifluoromethylphenyl)carbamoyl]-2-pyrazoline-4-carboxylate was the most potent, the I₅₀ value of which as 9·12×10⁻⁷ m . Variations in the activity in terms of log(1/I₅₀) were quantitatively analysed using a substituent parameter, showing that the higher the electron-withdrawing effect of the substituent, the higher was the activity. The substituent effects were similar to those on insecticidal activity against the Americal cockroach. The higher the inhibitory activity against Ca²⁺ uptake, the higher seemed to be the insecticidal activity. Methyl(4S) - 3 - (4 - chlorophenyl) - 4 - methyl - 1 - [N - (4 - chlorophenyl)carbamoyl] - 2 - pyrazoline -4-carboxylate had higher inhibitory activity against Ca²⁺-uptake and higher in-secticidal activity than the R-isomer, but the difference was greater in theCa²⁺-uptake system.     

Synthesis and insecticidal activity of 3-(haloalkyl-1,3-dienyl)-2,2-dimethylcyclopropanecarboxylates

New 2,2-dimethylcyclopropanecarboxylic acids bearing halogenated 1,3-alkadienyl substituents at position 3 of the cyclopropane ring were synthesised and the insecticidial activities of their 3-phenoxybenzyl and α-cyano-3-phenoxybenzyl esters against housefly (Musca domestica), Colorado potato beetle (Leptinotarsa decemlineata) and Egyptian cotton leafworm (Spodoptera littoralis) were determined. The activity of these compounds varied according to the relative position of the halogen substituents on the diene chain. The observed changes of activity with the structure of the side chain are discussed in terms of the coplanarity of the conjugated double bonds.     

Effect of insecticide—synergist combinations on the survival of Spodoptera exigua

The chitin synthesis inhibitors diflubenzuron and teflubenzuron have recently become ineffective for the control of Spodoptera exigua in floricultural crops. An extended laboratory test with second-instar larvae of S. exigua on Vicia faba plants was carried out to determine the influence of synergists on the biological activity of three benzoylphenyl ureas (BPUs). The co-application of piperonyl butoxide, an oxidase inhibitor, did not increase the activity of diflubenzuron, teflubenzuron or hexaflumuron. The best results were obtained with diethyl maleate, for suppressing glutathione S-transferase activity, and with dimethoate, as a hydrolase inhibitor. A joint application of diflubenzuron (at a concentration which resulted in 43% survival) with diethyl maleate or dimethoate gave only 6.2 and 8.9% surviving larvae, respectively. In addition, development to fourth-instar larvae was inhibited. The more stable teflubenzuron was synergized by both compounds to a much lesser extent than diflubenzuron. None of the synergists had a significant effect on the activity of hexaflumuron, which was the most potent insecticide of the three BPUs tested against S. exigua.     

Synthesis,fungicidal activity and structure-activity relationships of a series of 1-(3-pyridyl)-1-substituted-but-3-yn-1-ols

A series of 1-(3-pyridyl)-1-substituted-but-3-yn-1-ols and some related compounds were synthesised and tested for antifungal activity against eight phytopathogenic fungi of different taxonomic classes. High activity was shown in particular against Sphaerotheca fuliginea on Cucumis sativus. The compounds containing aromatic substituents gave the best results, not only in protectant but also in systemic and eradicant tests. The quantitative structure-activity relationship suggests that steric effects play an important role in determining fungicidal activity.     

Quantitative Structure–Activity Relationships of DDT-Type Compounds in a Sodium Tail-Current in Crayfish Giant Axons

Effects of DDT-type compounds including 1,1-bis(para-substituted phenyl)-2,2-dichlorocyclopropanes (DCC-series compounds) on sodium currents in crayfish giant axons were measured under voltage-clamp conditions. Variations in the activity to prolong the tail-current that was observed upon step repolarization of the membrane were quantitatively analysed by use of physicochemical parameters of aromatic substituents and regression analysis. Introduction of lengthy and narrow substituents was favourable to the activity. Variations in the activity were parabolically related to the hydrophobicity, optimum value being around that of H. DDT- and prolan-series compounds were 2–3 times more active than DCC-series compounds when other structural factors were the same. Insecticidal activity of the compounds was linearly correlated with the tail-current activity when the hydrophobic factor was separately considered. The insecticidal activity of DDT-series compounds was 2·5 times higher than that of others when the other factors were the same. © 1997 SCI.     

含香豆素基团的二氯丙烯类衍生物的合成及杀虫活性

以丙二酸二乙酯、间苯二酚和1,1,3-三氯丙烯等为原料,经取代、环合、缩合等反应合成了9个含有香豆素基团的二氯丙烯类衍生物,化合物结构经IR、 1H NMR、 MS及元素分析确证。初步的生物活性测定结果表明,该类化合物在400 mg/L质量浓度下对小菜蛾Plutella xylostella有较好的杀虫活性,其中化合物 5e 对小菜蛾的致死率达到93%。     

Synthesis and herbicidal potential of substituted aurones

BACKGROUND: With the objective of exploring the herbicidal activity of substituted aurones, a series of 4,6‐disubstituted and 4,5,6‐trisubstituted aurones were synthesised, and their herbicidal activities against Brassica campestris L. and Echinochloa crusgalli (L.) Beauv. were evaluated in laboratory bioassays. Effects of some of the compounds were evaluated on seed germination. The most active compounds in the laboratory were evaluated in the greenhouse. RESULTS: The compounds were characterised by ¹H NMR, ¹³C NMR and HRMS; some of them were further identified by IR. A (Z)‐configuration was assigned to the aurones, based on spectroscopic and crystallographic data. Bioassay results of root growth showed that the aurones had a moderate herbicidal activity against the dicotyledonous plant Brassica campestris. (Z)‐2‐Phenylmethylene‐4,6‐dimethoxy‐3(2H)‐benzofuranone(6o) was the most active compound, with 81.3 and 88.5% inhibition at 10 and 100 µg ml^?1 respectively, equal to the activity of mesotrione. Some of the aurones possessed some inhibition of germination on several plant species. For glasshouse tests, the substituted aurones had lower herbicidal activity than metolachlor and mesotrione. CONCLUSION: It is possible that aurone derivatives, which possess structures different from those of the commercial herbicides, may become novel lead compounds for the development of herbicides against dicotyledonous weeds with further structure modification. Copyright © 2012 Society of Chemical Industry     

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。     

含5-苯基2-呋喃环的3(2H)哒嗪酮类衍生物的合成与生物活性(I)(英文)

为探索新的农药先导化合物,经取代苯基呋喃甲酰氯与5-肼基-3(2H)哒嗪酮反应,得到15个未见文献报道的含呋喃环3(2H)哒嗪酮类化合物,其结构均通过了红外光谱、核磁共振氢谱和元素分析确认。初步生物活性测定结果表明,目标化合物具有良好的杀菌活性,但杀虫活性较弱。其中化合物3k在50 mg/L时对灰霉病菌的抑制率为86.29%±1.51%,与对照药剂腐霉利相当。初步的构效关系研究结果显示,苯环上取代基的种类和位置对杀菌活性有重要影响。     

Insect growth regulating activity of 1,5-disubstituted imidazoles against Bombyx mori and Oncopeltus fasciatus

Seventeen 1,5-disubstituted imidazoles possessing a variety of substituents were tested on Bombyx mori and Oncopeltus fasciatus. All compounds induced precocious metamorphosis from 4th-instar larvae of B. mori. Of the compounds tested, 1-benzyl-5-[(E)-2,6-dimethyl-1,5-heptadienyl]imidazole (KK-42) was the most active against B. mori larvae. However, none of the compounds induced precocious metamorphosis in O. fasciatus nymphs, although several showed delayed toxicity. Treated nymphs died during or immediately after the moult. A series of 1-isobutylimidazoles exhibited high activity against O. fasciatus, whereas KK-42 was inactive even at high doses. There was no apparent correlation between the ability of imidazoles to cause precocious metamorphosis in B. mori and the delayed toxicity for O. fasciatus.