Structure—activity relationships of fungicidal acetylenic sulphones

Regression analysis in the l-alkylsulphonyl-2-arylacetylene series yielded significant correlations of antifungal activity against six microorganisms with certain physicochemical parameters (electronic effects, lipophilicity and steric factors). Fungicidal activity is enhanced by introducing electron-withdrawing substituents in the aryl nucleus, whereas variation of the lipophilic parameter reveals an optimum value. The results obtained indicate a mechanism of action based on a reaction of the compounds with nucleophiles present in the fungal cells, which was confirmed by determining the second-order rate constants of the reaction between 1 -alkylsulphonyl-2-arylacetylenes and the model nucleophile 4-nitro(thiophenol). The lipophilic para-meter was also determined experimentally using thin-layer chromatography. Regression analysis with this completely experimental set of parameters regression gave highly significant results in close agreement with those obtained above.     

Structure—activity relationships of pyridylcarbamates active against both benzimidazole-sensitive and -resistant isolates of Botrytis cinerea

A series of pyridylcarbamates showed high potency against cucumber gray mould (Botrytis cinerea Pers.). The most potent compound, propargyl-N-(6-ethyl-5-iodo-2-pyridyl)carbamate was effective against an isolate sensitive to benzimidazole and dicarboximide fungicides as well as against an isolate resistant to both types of compound. QSAR analyses and molecular modelling studies were carried out to investigate the structural requirements for highly active compounds and the structural feature of the binding site of each strain. Significantly different QSAR equations were obtained only for substituents at the 6-position of the pyridine ring. An ethyl-sized pocket or an ethyl terminal recognition was suggested in the case of the sensitive or resistant isolate respectively. These results could explain the phenomenon of negatively correlated cross-resistance between benzimidazoles and N-phenylcarbamate fungicides. Substituent effects at the 5- or 2-position were governed by steric factors. Substituent effects at the 3-position were explained by steric hindrance or by conformational effects. The propargyl-substituted compound above was the most desirable one from the viewpoint of QSAR.     

Occurrences of Ceratocystis ulmi in Norway1

Norway (in contrast to Denmark and Sweden) has so far had only a few outbreaks of Dutch elm disease, all in the southern part of Norway (cities of Oslo and Drammen) on one or a few Ulmus glabra trees in city parks, not far from harbours and railways. Scolytus laevis endemic to Norway is the only potential vector found in the diseased trees. Transmission of the fungus through root grafts cannot be disregarded. The fungus is currently considered a dangerous foreign organism in Norway, subject to treatment according to the Norwegian phytosanitary regulations. Control measures, aiming at eradication, have been applied in all known cases of attack. Removal and destruction of diseased trees, stump treatment with herbicide, and covering of stumps with soil, have apparently been successful measures.     

Structure—activity relationships in pyrethroid esters derived from substituted 2-phenoxy-3-methylbutanoic acids

Non-cyclopropane pyrethroid esters of different substituted 2-phenoxy-3-methylbutanoic acids have been synthesised using the three alcohols—3-phenoxybenzyl alcohol, α-cyano-3-phenoxybenzyl alcohol and 3, 4-methylene-dioxybenzyl alcohol. Among the 35 esters synthesised and tested against Culex quinquefasciatus Say, the Bancroftian filariasis vector, for both larvicidal and adulticidal activities, α-cyano-3-phenoxybenzyl 2-(4-fluorophenoxy)-3-methylbu-tanoate, with an LC₅₀ value of 2.5 × 10^?3 mg litre^?1 for larvicidal activity, and α-cyano-3-phenoxybenzyl-2-(4-chlorophenoxy)-3-methylbutanoate, with an LD₅₀ value of 30 times; 10^?4 ug insect^?1 for adulticidal activity, were found to be as effective as fenvalerate, a well-known non-cyclopropane pyrethroid ester. Structure-activity studies showed that the insecticidal activity is dependent on the nature and position of the substituent in the phenyl ring of the acid moiety and also on the type of alcohol moiety.     

Formation of perithecia of Ceratocystis ulmi on natural and synthetic nutrient media

Ceratocystis ulmi formed fertile perithecia on 17 of 37 culture media tested, including many of the (autoclaved) natural substrates, but not on Saboraud's media or White's medium and not on potato dextrose agar (Table 1). Later, perithecia formed abundantly on four of eight variants of Zentmyer-Tchernoff agar medium (Table 2). This appears to be the first report on perithecia ofC. ulmi on an agar medium to which only synthetic nutrients were added. Both normal-strength and 110 diluted media gave perithecia. If only the sugar or only the asparagine-plus-salts were diluted, none or very few perithecia formed. Tenfold dilution of the vitamins did not affect results. Light did not prevent formation of perithecia.Samenvatting Ceratocystis ulmi vormde rijpe peritheciën op 17 van de 37 getoetste voedingsbodems, maar in het begin alleen op enkele van de (gesteriliseerde) natuurlijke voedingsbodems, niet op Sabourauds of Whites agar en evenmin op aardappel-dextrose-agar (Table 1). In latere proeven werden rijkelijk peritheciën gevormd op 4 van de 8 varianten op Zentmyer-Tchernoff-agar (Tabel 2).Waarschijnlijk is dit de eerste vermelding van vorming van peritheciën vanC. Ulmi op agar waaraan uitsluitend synthetische voedingsstoffen zijn toegevoegd. Zowel op de standaard-concentratie als op een tienvoudige verdunning van de voedingsstoffen werden peritheciën gevormd. Als alleen de glucose of alleen de asparagine-plus-zouten verdund waren, werden er geen of zeer weinig peritheciën gevormd. Tienvoudige verdunning van de vitaminen beïnvloedde de resultaten niet. Licht remde de vorming van peritheciën niet.A contribution of the Massachusetts Agricultural Experiment Station.     

The control in vitro of Ceratocystis ulmi by amine cations

Of 60 amine cations tested in vitro for activity against Ceratocystis ulmi, that of methyl benzimidazol-2-ylcarbamate (carbendazim) showed the highest activity, this being constant with three different associated anions. Some guanidines, 2-nitro-morpholine and 2-(thiazol-4-yl)benzimidazole (thiabendazole) showed considerable activity but a large group of alkylamines, 1-methylalkylamines and poly-amines were relatively inactive.     

Quantitative structure—activity relationships for nicotinanilide molluscicides

Structure-activity correlations for the toxicity of nicotinanilides to Biomphalaria glabrata have been studied in terms of partitioning, charge transfer and steric properties. Partition coefficients or πNA values (substituent constants for nicotinanilides, reflecting the influence on the partition coefficient of a substituent on the parent molecule) have been shown to contain a significant electronic component and to be related to chromatographically determined R_M values (derived from a relationship between the partition coefficient and R_F value for liquid-liquid chromatographic systems). There was no overall correlation between LC₅₀ values and partitioning, electronic or steric effects. However, for ten 4′-substituted nicotinanilides, the LC₅₀ values correlated significantly with partitioning, an increase in lipophilic character leading to an increase in biological activity. The greater activity of the unsubstituted parent compound could not be explained by purely advantageous steric effects but the 4′-position may be an important metabolic site. Use of compounds labelled with deuterium failed to clarify this point because no isotope effects were observed.     

Length and diameter of xylem vessels as factors in resistance of elms to Ceratocystis ulmi

Conductivity of the vascular system of 2-year-old shoots as regards air and water was higher in susceptible than in resistant elms. The xylem vessels of resistant elms were relatively shorter and the percentage of short vessels was greater than in susceptible elms. The percentage of vessels with a large diameter was smaller in resistant elms than in susceptible ones. These results might explain the limited spreading of the spores in the new annual ring of resistant elms.Samenvatting Tweejarige scheuten van resistente iepen bleken lucht en water minder snel door te laten dan vergelijkbare scheuten van vatbare iepen. De vaten bij resistente iepen waren relatief kort en het percentage korte vaten was groter dan bij vatbare iepen. Het percentage grote vaten was kleiner bij resistante iepen dan bij vatbare. Dit zou een verklaring kunnen zijn voor de relatief geringe verspreiding van de sporen in de nieuwe jaarring van de resistente iepen.     

The pyrethrins and related compounds. Part XLII:Structure–activity relationships in fluoro-olefin non-ester pyrethroids

A series of compounds containing fluorine atoms in place of hydrogen in olefinic non-ester pyrethroids has been synthesised using a route based on novel intermediates, ie 2-fluoroallyl acetates, which are coupled with aryl Grignard reagents, and tested against several insect species. In most cases, after introduction of fluorine at the olefinic position, the activity remains high in both the 1-aryl-1-(3-arylprop-2-enyl)cyclopropane and the (1-aryl-4-arylbut-2-enyl)cyclopropane series. In particular, the former series have potential as soil insecticides, because in tests against Diabrotica balteata, activities were high, and dose-transferability factors were increased by the introduction of fluorine. © 1999 Society of Chemical Industry     

1-alkylcyclopropanecarboxylates: An extension of pyrethroid structure—activity relationships

1-Alkylcyclopropanecarboxylic acids are synthesised by thermolysis of 1-pyrazolines prepared by 1,3-dipolarcycloadditions of diazoalkanes. The insecticidal and acaricidal activities of 14 pyrethroid esters of these acids are considered in relation to the influence of steric and metabolic factors on activity. 1-Alkyl compounds are less active than esters with no alkyl group at position 1, contrary to expectations, and also less active than the corresponding 2-alkyl esters.     

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.     

Organosilane insecticides. Part II: Chemistry and structure—activity relationships

Silicon effectively substitutes for quaternary carbon in etofenpr ox-type insecticides; the resulting dimethyl-4-ethoxyphenyl-3-(4-fluoro-3-phenoxyphenyl)propylsilane is a broad-spectrum insecticide with extremely low toxicity to fish. Four regions of this new silane insecticide have been systematically altered. The methyl groups on silicon appear to be critical for activity. Replacement of the fluorine with hydrogen results in a substantial loss of activity. The aromatic rings of the phenoxyphenyl fragment are best tethered by oxygen or carbonyl, the methylene and nitrogen analogs being of very low toxicity to the test species. The activity ranking of the methylene and carbonyl tethers is opposite to that found for ester pyrethroids. The relationship of insecticidal activity to the aromatic substituent para to the silicon atom has been found to correlate with the molar refractivity of the substituent. Replacement of a tetra-substituted carbon atom with a silicon atom can simplify construction of test compounds and thus be advantageously used in the exploration of structure—activity relationships. A novel method for preparing allylbenzenes from aromatic aldehydes was also developed.     

Structure-activity relationships in triorganotin biocides: The influence of the anionic radical

Bioassay data are reported for seven triorganotin compounds (R₃SnX), in which R=phenyl, cyclohexyl, or 2-methyl-2-phenylpropyl, and × is the anionic form of the organic chelating ligands quinolin-8-ol, quinoline-8-thiol, 1,3-diphenylpropane-1,3-dione, or 3-hydroxyflavone, when tested against an organophosphorus-resistant species of the two-spotted spider mite (Tetranychus urticae), the potato blight fungus (Phytophthora infestans), and the vine downy mildew fungus (Plasmopara viticola). The relationship between the activity and the co-ordination number of the tin atom is discussed, and it is shown that the anionic group × can, in some instances significantly affect the biological properties.     

Simulation of predator—prey relationships in an acarine system

Simulation with a computer can be an aid in the analysis of complex ecological processes. When such processes bear upon the behaviour of individual plants or animals, they often depend on chance variables. Such stochastic processes cannot be correctly simulated with a deterministic model, when there are non-linear relationships between output variables and chance variables. On the other hand, simulation with a stochastic model using a random function generator has to be repeated several times to obtain reliable expectation values of the output variables. A method is described for simulation of stochastic processes in one run, which provides acceptable expectation values. The method is applied in a program for simulation of a predation process, which occurs when the predacious mite, Typhiodromus occidentalis, preys on eggs of the spider mite Tetranychus urticae. The results are compared with those obtained by regular deterministic and stochastic simulation.     

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     

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.     

Quantitative structure–activity relationships in aquatic toxicology

Quantitative structure–activity relationships (QSARs) enable the toxicity of aquatic pollutants to be predicted from their physicochemical properties. This paper reviews several techniques that can be used to obtain QSARs and examples of QSAR studies are presented for some important groups of aquatic pollutants; reactive organic halides, anilines, phenols and for some relatively unreactive, non-ionised compounds. Finally the possibility of applying predicted toxicities in environmental hazard assessment is discussed.     

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.