Chemical structure and physical properties of candidate insecticides in relation to residual toxicity to adult mosquitos

Data are presented on changes in physical properties and insecticidal activity resulting from modifications in chemical structure in two groups of compounds. The first group consists of propoxur and three closely related N-methylcarbamates and the corresponding N-acetyl compounds The parent compounds are all highly toxic to adult mosquitos by topical application in solution and deposits from water-dispersible powder formulations on plywood and plaster of Paris panels have long residual activity. N-acetylation is not accompanied by excessive loss of toxicity to mosquitos, but increases volatility to the extent that none of the four N-acetyl derivatives can be considered as potential residual insecticides. The second group consists of tetrachlorvinphos and related vinyl phosphates and vinyl phosphorothionates which show a wide range of toxicity both to adult mosquitos and to mammals.     

Effects of alkyl groups attached to the carbamoyl nitrogen atom of an N-arylcarbamoylpyrazoline on insecticidal activity

N-Alkylated analogs (C₁–C₃) of an N-arylcarbamoylpyrazoline were prepared. The introduction of these alkyl groups completely changed the crystal structure in respect of the torsion angle of the amide C–N bond of the non-alkyl compound. The introduction of methyl and ethyl groups slightly, and that of an isopropyl group markedly, decreased insecticidal activity against American cockroaches and house flies. Conformational analyses of the compounds suggested that the insecticidally active conformer of this class of compounds is in the anti-position regarding the N′–C(=O) and N-aryl bonds in which the non-alkyl compound is energetically the most stable. The most stable conformers of the alkylated compounds are in the syn-position, and these compounds would interact with target sites in the less stable anti-form. © 1999 Society of Chemical Industry     

Synthesis and insecticidal evaluation of N-substituted 2-nitroiminoimidazolidines

N-substituted and N,N′-disubstituted 2-nitroiminoimidazolidines were prepared from 2-nitroiminoimidazoline. The feeding-contact and systemic activities as insecticides of some of these new compounds have been evaluated. © 1998 Society of Chemical Industry     

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.     

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.     

10种N-取代氨基香豆素的合成及生物活性

基于结构拼接思想,设计合成了10个N-取代氨基香豆素类化合物,并测定了其抑菌及除草活性。6-硝基香豆素经Fe/NH4Cl还原得6-氨基香豆素,再与不同醛缩合得Schiff碱,最后经硼氢化钠还原制得10个N-取代氨基香豆素类化合物(4a~4J),其中9个未见文献报道,其结构均经红外光谱、核磁共振氢谱和质谱确认。抑菌活性测试结果表明,所有化合物对苹果腐烂病菌Valsa mali、葡萄白腐病菌Coniothyrium diplodiella、棉花枯萎病菌Fusarium oxysporium和柑橘炭疽病菌Citrusanthrax bacteria均有一定抑制作用,其中 4e 的抑菌活性最强,对苹果腐烂病菌和柑橘炭疽病菌的EC50值分别为7.53和12.93 mg/L,对其余2种植物病原菌的EC50值均小于25 mg/L;化合物 4f 次之,对苹果腐烂病菌和葡萄白腐病菌的EC50值均约为11 mg/L。除草活性测试结果表明,除 4f 外,所有目标化合物均有一定除草作用,其中 4c 的活性最强,100 mg/L下对反枝苋Amaranthus retroflexus种子根、茎生长的抑制率均为99%。     

Antimicrobial activity of some N-(arylalkyl)maleimides

A series of N-(arylalkyl)maleimides was prepared for the reaction of maleic anhydride and N-(arylalkyl) amines, and their antimicrobial activities were examined. All compounds exhibited antibacterial activity against gram-positive bacteria such as Bacillus subtilis and Staphylococcus aureus. Almost all compounds exhibited antibacterial activity against the gram-negative bacterium, Escherichia coli, but were inactive against Pseudomonas aeruginosa. Activities against gram-positive bacteria were independent of the nature of the substituent on the benzene ring or the length of alkyl group, but that against gram-negative bacteria was influenced by these parameters. All N-(arylalkyl)maleimides showed activity against yeasts and mycelial fungi.     

From synthetic control to natural products: a focus on N‐heterocycles

Natural products containing a N‐heterocycle motif are widespread in nature and medicinal plants, in particular, have proved to be a source of almost unlimited N‐derived structures with high molecular diversity. Because of their intrinsic potential for use in both biomedical and agricultural applications, there is a general need for new compounds and for the synthesis of ‘natural‐inspired’ analogues. Importantly, transition of a natural product from discovery to a ‘market lead’ is associated with an increasingly challenging demand for more of the compound, which cannot be met by isolation from natural plant sources, often due to low extraction yields and uneven availability of the plant source itself. Synthesis remains the most reliable approach to provide valuable products for the market. In this review, a comprehensive overview of our contribution to synthetic access to N‐derived natural products is given. Major strengths of the proposed methodologies are discussed critically. © 2019 Society of Chemical Industry     

Antimicrobial activity of some N-(fluorophenyl)maleimides

A variety of N-(fluorophenyl)maleimides were prepared from the reaction of maleic anhydride and fluorophenylamines, and their antimicrobial activities examined. N-(Monofluorophenyl)maleimides exhibited antibacterial activity against Bacillus subtilis, Staphylococcus aureus and Escherichia coli, and no activity against Pseudomonas aeruginosa. These compounds also showed antifungal activity against Aspergillus niger, Penicillium citrinum, Cladosporium cladosporioides and Aureobasidium pullulans. All N-(fluorophenyl)maleimides tested showed activity against yeasts.     

Inhibitors of choline acetyltransferase as potential insecticides

Choline acetyltransferase (E.C.2.3.1.6) catalyses the synthesis of acetylcholine and is therefore a target for a new insecticide. We have prepared a variety of compounds, mainly choline analogues, as inhibitors of this enzyme. One of these, 2-isothiocyanatoethyltrimethylammonium iodide, has a K_i of 0.06 μM (K_m for choline is 150 μM ) and is apparently the most powerful inhibitor known for this enzyme. Although some of our compounds are insecticidal we believe, on the basis of electrophysiological studies, that they act, not on choline acetyltransferase, but on the acetylcholine receptor of the insect.     

寡肽手性膦酸酯硫脲的合成及其抗烟草花叶病毒活性

为了寻找新型具有抗烟草花叶病毒 (TMV) 作用的化合物,在前期研究工作基础上,以取代苄胺、氨基酸及亚膦酸二烷基酯等为原料,按照由C端向N端依次接肽的合成策略,采用缩合剂O-苯并三氮唑-四甲基脲六氟膦酸酯 (HBTU) 合成酰胺的方法,获得了18个新型寡肽手性膦酸酯硫脲,其结构均经红外光谱、(1H、13C、31P、19F) NMR及元素分析确证和表征,并首次研究了该类化合物抗TMV活性。结果表明:部分目标物对TMV具有较高治疗作用,其中化合物 5i 、 5j 和 5p 在500 μg/mL时对TMV侵染的活体治疗作用效果分别为52.6%、55.7%和56.1%,接近对照药剂宁南霉素 (55.4%)。值得进一步结构改造和构型优化,并在此基础上进行作用机制研究。     

Structure-activity relationships in fungitoxicants related to triforine and chloraniformethan. III. A quantitative hansch analysis

Quantitative structure-activity relationships in several series of fungitoxic N-(1-substituted-2,2,2-trichloroethyl)formamides and bis[1-(2,2,2-trichloroethyl)formamides] were investigated by the Hansch method, employing partitioning data determined by reversed-phase thin-layer chromatography and electronic parameters calculated by the Hückel Molecular Orbital method. The activity of compounds applied as root-drenches against Erysiphe graminis on barley correlated with their partitioning properties alone, but electronic properties of the aromatic derivatives were also influential in leaf-spray tests. Possible factors governing the activity of the compounds are discussed. It is tentatively proposed that the biologically active centre of triforine and related aliphatic compounds includes the XCHNHCO grouping (where X = heteroatom), whereas that of chloraniformethan and its aryl analogues incorporates the grouping RXCHNHCO (where RX = a conjugated system capable of accepting pi-electrons from an electron donating receptor).     

Synthesis and fungicidal activity of N-(p-sulfonylphenyl)-N1 -carbamoylureas

A series of 11 N-(p-sulfonylphenyl)-N¹-carbamoylureas was prepared by reaction of 1,6-diphenyl-2,4-dioxohexahydro-s-triazine with chlorosulfonic acid and thionyl chloride. The resultant N-(p-chlorosulfonylphenyl)-N¹-carbamoylurea was subsequently condensed with amines, butanol, hydrazine and sodium azide. The hydrazide was reacted with carbonyl compounds and the azide with trimethyl phosphite. The products were tested for in-vivo fungicidal activity against barley powdery mildew (Erysiphe graminis); the acetone hydrazone derivative showed the highest activity. © 1998 SCI.     

2-氧代-2-苯基乙磺酰胺化合物组合合成与杀菌活性研究

为了快速获得具有高效杀菌活性的先导化合物,利用组合化学与传统合成方法相结合的方案,研究了N-取代-2-氧代-2-苯基乙磺酰胺类化合物对灰霉病菌的杀菌活性。首先以苯乙酮为原料,经过磺化、氯化反应,制备得到2-氧代-2-苯基乙磺酰氯,再分别与苯胺、苄胺和烷基胺组合库反应,制备了33个组合库,其中包含105个化合物,收率在60%~90%之间,纯度在70%~95%之间。筛选其中的10个活性库进行平行合成,得到29个化合物,又对其中10个活性化合物进行了纯化与结构鉴定。最后用灰霉病菌Botrytis cinerea对所有组合库与化合物进行离体与活体双重筛选,快速确定了高活性先导化合物,为进一步的结构优化奠定了基础。     

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     

Selectivity of diacylhydrazine insecticides to the predatory bug Orius laevigatus: in vivo and modelling/docking experiments

BACKGROUND: Knowledge of pesticide selectivity to natural enemies is necessary for a successful implementation of biological and chemical control methods in integrated pest management (IPM) programmes. Diacylhydrazine (DAH)‐based ecdysone agonists, also known as moulting‐accelerating compounds (MACs), are considered to be a selective group of insecticides, and their compatibility with predatory Heteroptera, which are used as biological control agents, is known. However, their molecular mode of action has not been explored in beneficial insects such as Orius laevigatus (Fieber) (Hemiptera: Anthocoridae). RESULTS: In this project, in vivo toxicity assays demonstrated that the DAH‐based RH‐5849, tebufenozide and methoxyfenozide have no toxic effect against O. laevigatus. The ligand‐binding domain (LBD) of the ecdysone receptor (EcR) of O. laevigatus was sequenced, and a homology protein model was constructed that confirmed a cavity structure with 12 α‐helices, harbouring the natural insect moulting hormone 20‐hydroxyecdysone. However, docking studies showed that a steric clash occurred for the DAH‐based insecticides owing to a restricted extent of the ligand‐binding cavity of the EcR of O. laevigatus. CONCLUSIONS: The insect toxicity assays demonstrated that MACs are selective for O. laevigatus. The modelling/docking experiments are indications that these pesticides do not bind with the LBD‐EcR of O. laevigatus and support the supposition that they show no biological effects in the predatory bug. These data help in explaining the compatible use of MACs together with predatory bugs in IPM programmes. Copyright © 2012 Society of Chemical Industry     

Negative cross-resistance to N-phenylanilines in benzimidazole- resistant strains of Botrytis cinerea,Venturia nashicola and Venturia inaequalis

A new series of compounds with high contra-selective activity against benomyl-resistant fungal strains was found among ring-substituted N-phenyl-anilines. Hydrophobic substitution in one of the benzene rings, together with the secondary amine character of the molecule, are important factors for high fungitoxicity. The sensitivities of benomyl-resistant isolates to some representatives of the N-phenylanilines equal or even surpass their sensitivity to diethofencarb or MDPC. The negative cross-resistance with benzimdazole fungicides is valid for strains of Botrytis cinerea, Venturia nashicola and Venturia inaequalis. The strains of B. cinerea with double insensitivity to benzimidazoles and phenyl-carbamates are insensitive also to N-phenylanilines. However, the similarly double-insensitive strain of V. nashicola was found to be just as sensitive to the N-phenylanilines tested as the strain resistant only to benzimidazoles. The latter result revealed an important bonus compared with diethofencarb. Preventive application of one of the most active representatives of the N-phenylanilines to young cucumber plants was effective against infection with benomyl-resistant isolates of B. cinerea. Moderate apical translocation after root-dipping was also observed.     

Fungitoxicity of 5-aminoisoxazole-4-thiocyanate derivatives

3-Methyl-5-(acyl/alkyl)aminoisoxazole-4-thiocyanates were prepared by rhodanation of N-acyl/alkyl-3-methyl-5-isoxazolamines. These products were tested for antifungal activity against a series of phytopathogenic fungi of different taxonomic classes. Some of the compounds showed interesting in-vitro activity. The more active compound in the in-vitro test displayed a moderate preventive activity against Plasmopara viticola, Alternaria solani and Pyricularia recondita.     

Muscarinic Agonists as Insecticides and Acaricides

A series of known agonists of the mammalian muscarinic receptor were prepared and evaluated for their insecticidal potential. It was discovered that pests such as Nilaparvata lugens (brown planthopper), Nephotettix cincticeps (green leafhopper), Tetranychus urticae (two-spotted spider mite) and Aphis gossypii (cotton aphid) were particularly sensitive to most of these compounds. Several analogs proved to be extremely active, surpassing commercial standards in some of the laboratory bioassays. These compounds exhibited a range of potencies for the insect (Musca) muscarinic receptor. Addition of GTP significantly reduced the affinity of the most potent analog for the Musca mAChR, indicating the compound functions as an agonist in insect tissue. Regression analysis indicated that significant relationships exist between displacement of [³H]QNB at the Musca muscarinic receptor and whole organism toxicity to three insect and one mite species. The results suggested that the insect muscarinic receptor represents a viable target site for insecticidal action. © 1997 SCI.     

New nitrogen-containing herbicides

Acylhydroxylamines have attracted general attention following the successful development of the highly-efficient linuron group herbicides¹ and a search for new herbicides from among this class of compounds has led to the development of three new groups of herbicides^2-7.

• 1 O-Acyl-N-carboalkoxy-N-arylhydroxylamines (acylates).
• 2 N-Carbamoyl-N-arylhydroxylamines (e.g. meturine).
• 3 Hydroxylamino derivatives of s-triazine.