Effects of organosilicon pyrethroid‐like insecticides on nerve preparations of American cockroaches and crayfish

Quaternary organosilicon pyrethroid‐like ethers (five compounds) and alkanes (three compounds) were used for neurophysiological tests. Their activities in inducing repetitive firing in the central nervous cord of the American cockroach (Periplaneta americana) were evaluated by an extra‐cellular recording method. The ethers were more active than the corresponding alkanes. The ability of the compounds to cause conduction blockage was also measured using the same nerve preparations, but the effects were too weak to allow definitive activity values to be determined. The compounds prolonged the sodium tail‐current in the crayfish giant axon under voltage clamp conditions. The rate of decay of the tail‐current changed in parallel with the reported insecticidal activity against P americana. These findings indicated that tail‐current activity was the most useful nerve parameter in predicting insecticidal activity. Regression analysis of the numerical data together with those reported for other alkanes revealed that the higher the tail‐current activity, the higher the insecticidal activity when a structural feature and the hydrophobicity were considered separately. The insecticidal activity of the ethers was about seven‐fold higher than that of the alkanes with equivalent tail‐current activity and hydrophobicity. Variations in insecticidal activity were parabolically correlated with the hydrophobicity [(log P)_opt = 9.1] when other factors were similar. © 2001 Society of Chemical Industry     

Quantitative structure-activity studies of pyrethroids: 12. Physicochemical substituent effects of meta-phenoxybenzyl α,α-disubstituted acetates on insecticidal activity

The insecticidal activity of a series of m-phenobenzyl esters of iso-valeric and tert-butylacetic acids, the α-position of which was substituted with one of alkyl, alkoxyalkyl, alkoxy, benzyl, phenyl, phenoxy, and anilino groups, was measured by injection into American cockroaches under synergistic conditions to suppress possible oxidative and hydrolytic metabolism. Their neuroexcitatory activity on nerve preparations excised from the cockroaches was measured by an extracellular recording technique. The activities of the analogous esters of cyclopropanecarboxylic acids with a substituted vinyl side chain were also measured. The insecticidal activity was quantitatively analyzed with physicochemical parameters for the α-substituent or its counterpart of the acid moiety. Variations in the activity were related parabolically to both the hydrophobicity and the length of the substituent. The activity of compounds, the α-substituent of which is either a substituted phenyl or a phenoxy group, was about 10 times that of compounds with “physicochemically equipvalent” aliphatic substituents. α-Substitution with ring-substituted anilino groups, but not with N-methyl groups, enhanced the activity about 25 times, but the vinylcyclopropane structure raised the activity to about 60 times that of physicochemically equivalent aliphatic noncyclopropane substituents. Variations in the insecticidal activity were closely related to those in the neuroexcitatory activity when hydrophobic and steric factors were separated. The steric factor in addition to the hydrophobicity seemed to be important in the transport process.     

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.     

Binding activity of substituted benzyl derivatives of chloronicotinyl insecticides to housefly‐head membranes,and its relationship to insecticidal activity against the housefly Musca domestica

Variously substituted benzyl derivatives of chloronicotinyl insecticides were synthesized with a wide range of substituents including halogens, NO₂, CN, CF₃ and small alkyl and alkoxy groups at the ortho, meta and para positions, as well as multiple‐substituted benzyl analogues. Their binding activity to the α‐bungarotoxin binding site in housefly (Musca domestica) head membrane preparations was measured. Among the compounds tested, the activity of the meta‐CN derivative was the highest, being 20–100 times higher than those of imidacloprid, acetamiprid and nitenpyram. The synergized insecticidal activity against houseflies was also measured for selected compounds with the metabolic inhibitor, NIA16388 (propargyl propyl phenylphosphonate). For the nitromethylene analogues, including both benzyl and pyridylmethyl analogues, higher binding activity usually resulted in higher insecticidal activity. © 2000 Society of Chemical Industry     

Quantitative structure-activity analysis of larvicidal 1-(substituted benzoyl)-2-benzoyl-1-tert-butylhydrazines against Chilo suppressalis

The larvicidal activity of a number of 1-(substituted benzoyl)-2-benzoyl–1 -ten-butylhydrazines against the rice stem borer (Chilo suppressalis Walk.) was measured. Variations in the activity were examined quantitatively using physico-chemical substituent and molecular parameters and regression analysis. The results indicated that the molecular hydrophobicity and the electron-withdrawing inductive/ field effect of ontho substituents are favourable to larvicidal activity. The bulkiness of substituents at the meta and para positions was unfavourable to activity, substitution at the para position being more unfavourable than that at the meta position in terms of van der Waals' volume. The 2,3–, 2,5- and 2,6-disubstitution patterns were also unfavourable to activity. Reductions in larvicidal activity caused by the 2,6-,- 2,3,5- and 2,3,4,5-substitutions were greater than those induced by the 2,3- and 2,5-disubstitutions. When the sum of contributions from favourable effects is greater than that from unfavourable effects, the larvicidal activity is expected to be superior to that of the unsubstituted compound.     

Fungicidal activity of a series of chloroacetylanilidophosphonates

Nine diethyl chloroacetylanilidomethylphosphonates and ten diethyl α-(chloroacetylanilido)benzylphosphonates were prepared by N-chloroacetylation of the corresponding diethyl anilinomethyl- and anilinobenzylphosphonates. These were tested for antifungal activity against six phytopathogenic fungi. Most of the compounds showed moderate protective properties. No significant difference in activity was observed for compounds with an extra aryl ring substituent on the methylene group of the backbone. Compounds with electron-withdrawing substituents, especially chlorine, on the aniline site (R¹) showed higher fungicidal activity than the other compounds with electron-donating groups as substituents.     

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     

Quantitative structure–fungicidal activity relationships of N-(4-difluoromethoxybenzyl)­pyrimidin-4-amines against wheat and barley fungi

A set of N-(4-difluoromethoxybenzyl)pyrimidinamines with various substituents at the 4- and 5-positions of the pyrimidine ring and at the benzyl position were prepared, and their fungicidal activities against wheat brown rust, Puccinia recondita, and barley powdery mildew, Erisiphe graminis, were measured. Variations in each of these activities were quantitatively analysed by the use of physicochemical substituent parameters and a regression analysis. Each of these activities was parabolically correlated with the steric bulkiness of the pyrimidine substituents and with the bulkiness or the hydrophobicity of the benzylic substituents. © 1999 Society of Chemical Industry     

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.     

Changes in cross-resistance patterns of houseflies selected with natural pyrethrins or resmethrin (5-benzyl-3-furylmethyl (±)-cis-trans-chrysanthemate)

A pyrethrins-resistant strain of houseflies, 213ab, previously selected with a 1:10 (by wt.) mixture of natural pyrethrins and piperonyl butoxide, was further selected either with natural pyrethrins alone (strain NPR) or with resmethrin (strain 104). After 50 generations the two populations differed in their resistance to the natural and synthetic esters. Both were resistant to all pyrethroids. Part of strain NPR was immune and very much more resistant than strain 104 to the natural pyrethrins and allethrin, but it was only 2–3 times more resistant than strain 104 against the new synthetic esters resmethrin (5-benzyl-3-furylmethyl (±)-cis-trans-chrysanthemate), bio-resmethrin (5-benzyl-3-furylmethyl (+)-trans-chrysanthemate), pyresmethrin (5-benzyl-3-furylmethyl pyrethrate) and 5B2Me3FC (5-benzyl-2-methyl-3-furylmethyl (±)-cis-trans-chrysanthemate). Pretreatment of both strains with sesamex diminished but did not eliminate resistance. Synergism was greater in strain NPR, especially with natural pyrethrins and allethrin. Both strains had great resistance to DDT indicating that resistance to DDT and pyrethroids is linked. Differences in resistance to different compounds suggest that at least three factors can confer resistance, one of which, pen, delays penetration and two others involve detoxication, one py a on the acid side of the ester linkage and the other, py b, on the alcohol side. Natural pyrethrins and resmethrin select for different groupings of these factors. Treatment with resmethrin does not select for py b presumably because this mechanism cannot attack the resmethrin molecule. Similarly when piperonyl butoxide is added to the natural pyrethrins py b is inhibited and so removed from selection pressure. Under these conditions, the strain produced contains the same factors as one selected by resmethrin and so shows the same small resistance to natural pyrethrins alone.     

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.     

Insecticidal activity of the pyrethrins and related compounds. IX. 5-benzyl-3-furylmethyl 2,2-dimethylcyciopropanecarboxylates with non-ethylenic substituents at position 3 on the cyclopropane ring

The insecticidal activities against houseflies (Musca domestica L.) and mustard beetles (Phaedon cochleariae Fab.) of 29 new 5-benzyl-3-furylmethyl 2,2-dimethyl-cyclopropane-carboxylates are compared with those of the corresponding chrysanthe-mate (bioresmethrin) to assess the influence of non-ethylenic and isobutenyl substituents at position 3 of the cyclopropane ring. Of the new groups investigated, only 3-methoxyiminomethyl gives equal or enhanced activity; 3-(2-furyl) esters are moderately effective, but 3-phenyl and 3-alkoxycarbonyl compounds show weak activity. A 3-(2,2,2-trihaloethyl) compound was more active than compounds with other saturated groups, such as isobutyl.     

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     

Quantitative structure-activity studies of insect growth regulators: XVIII. Effects of substituents on the aromatic moiety of dibenzoylhydrazines on larvicidal activity against the Colorado potato beetle Leptinotarsa decemlineata

Larvicidal activity against the Colorado potato beetle Leptinotarsa decemlineata (Say) was measured for a series of N-tert-butyl-dibenzoylhydrazines having various substituents on the benzoyl (A-ring) moiety nearer to the tert-butyl group, with the other benzoyl (B-ring) moiety being unsubstituted. The effects of these substituent on the larvicidal activity were analyzed using classical quantitative structure-activity relationship (QSAR) procedures. The effects of substituents on the A-ring moiety on larvicidal activity were entirely different from those against the lepidopteran rice stem borer Chilo suppressalis (Walker) previously reported. Position-specific steric and hydrophobic effects, as well as certain substitution patterns, were likely to participate in modifying the larvicidal activity. The activity of para-substituted compounds was generally lower than that of un-, ortho- and meta-substituted compounds. Most multi-substituted compounds showed an activity equivalent to or lower than that of the unsubstituted compound. Among 46 compounds tested, the 2-sec-butoxy analogue was most potent against L decemlineata, although this compound had previously been shown to be only weakly active against C suppressalis.     

Three‐dimensional quantitative structure–activity relationship analysis of acyclic and cyclic chloronicotinyl insecticides

The binding activity of chloronicotinyl insecticides, including acetamiprid, nitenpyram and related compounds, to the nicotinic acetylcholine receptors (nAChR) of houseflies was measured. These compounds were defined as ‘acyclic’ compounds. Variations in the binding activity were analysed using comparative molecular field analysis (CoMFA) which is a technique for the analysis of three‐dimensional quantitative structure–activity relationships. The CoMFA results showed that steric interactions were more significant for the acyclic compounds than for imidacloprid and its derivatives (cyclic compounds). It was also shown that the acyclic compounds could bind to housefly‐nAChR in a similar manner to the cyclic compounds, and that the electrostatic natures of the acyclic amino‐ and cyclic imdazolidine‐moieties affected their binding activity. © 2000 Society of Chemical Industry     

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     

Structure–Activity Relationships of Herbicidal Aryltriazolinones

A series of substituted aryltriazolinones, known to inhibit protoporphyrinogen oxidase, were prepared and their structure–activity requirements at positions 4 and 5 of the aromatic ring investigated. A QSAR equation obtained for substituents at the 5 position identified the hydrophobicity term π and the Sterimol minimum width B₁ as the two parameters affecting in-vitro biological activity. Greenhouse pre-emergence activity correlated with in-vitro activity and the hydrophobicity term π of the substituent at that position. It was found that the phenoxy-4-oxyacetate group at aromatic position 5 was an outlier and had to be considered separately. SAR analysis of substituents at aromatic position 4 revealed that two different models were required to explain all observed substituent effects. In the first model, where the 5 position was occupied by hydrogen, the 4-chlorobenzyloxy group at aromatic position 4 gave the best compound. The second model, where the 5 position of the aromatic ring was occupied by a group other than hydrogen, resulted in a QSAR equation, previously derived, which links substituent effects at position 4 with π and with the electronic para inductive term F_p. In this model the chloro group provides optimum biological activity. The need to separate the aryltriazolinone herbicides into several different classes in order to explain their substituent effects at aromatic positions 4 and 5 could be rationalized if more than one binding conformation, within the same binding site, is possible. © 1997 SCI     

Imazethapyr inhibition of acetolactate synthase in Rhizobium and its symbiosis with pea

Acetolactate synthase (ALS) activity extracted from Rhizobium leguminosarum biovar. viciae has been characterized. The optimum pH for extraction was 7·6 and for the assay 7·0. The K_m for pyruvate was 7·2 mM , and the enzyme was saturated at 40 mM . An obligatory requirement of TPP and Mg²⁺ for full ALS activity was observed. Valine was the only branched-chain amino acid that caused ALS feedback inhibition. The specific activity of Rhizobium ALS was nearly 20 times the activity found in pea (Pisum sativum) leaves. Bacteroids from pea nodules also showed high ALS activity, and the nodule plant fraction had higher ALS activity than other plant tissues. ALS sensitivity to imazethapyr was also dependent on the source: ALS activity of free-living Rhizobium and bacteroids was slightly more tolerant than that of other pea tissues, but the differences were less than those found in rates of specific activity. It is proposed that the high ALS activity expressed by Rhizobium, both as free-living bacteria and as bacteroids, is related to the growth tolerance of rhizobia to imazethapyr and is also related to the relative tolerance of symbiotic pea plants. © 1998 SCI     

Insecticidal activity of the pyrethrins and related compounds X 5-benzyl-3-furylmethyl 2,2-dimethyicyclopropanecarboxylates with ethylenic substituents at position 3 on the cyclopropane ring

The insecticidal activities against houseflies (Musca domestica L.) and mustard beetles (Phaedon cochleariae Fab.) of the chrysanthemate bioresmethrin, and of 31 related 5-benzyl-3-furylmethyl 2,2-dimethylcyclopropanecarboxylates with alkenyl, alkadienyl or alkoxycarbonylalkenyl substituents at position 3 of the cyclopropane ring are compared to determine the relative influence of the isobutenyl sidechain (as in chrysanthemates) and of the other side chains. Several substituents, in particular (E)- or (Z)-butadienyl or -pentadienyl, give considerably greater activity than isobutenyl but alkoxycarbonyl compounds are less potent.     

Activity of 2-(1-alkenyl)-3-hydroxy-1,4-naphthoquinones and related compounds against Musca domestica

A series of 2-(1-alkenyl)-3-hydroxy-1,4-naphthoquinones has been prepared and their toxicities assessed against Musca domestica. By comparison with analogous compounds having saturated 2-alkyl substituents, or unsaturated substituents with an unconjugated double bond (e.g. lapachol), it was demonstrated that the α-unsaturation of the substituent is responsible for a significant increase in the toxicity. The effect of the compounds against several other insect species and Tetranychus urticae follows completely different patterns.