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     

Design,synthesis and structure–activity relationships of novel ALS inhibitors

The paper describes the biophore models of sulfonylurea, imidazolinone, triazolopyrimidinesulfonamide and 5‐pyrimidyltriazolo‐3‐sulfonamides established by the Apex‐3D method. A series of N‐phenylsulfonyl‐N ′‐(thiadiazol‐2‐yl)oxamides and three types of triazolopyrimidinesulfonamide were synthesised and their herbicidal activities determined to assess the validity of the model. In general, the model gave useful leads to activity, although the actual level was not always predicted accurately. In only a few cases did compounds predicted as being active prove to be inactive in the bioassay, and compounds with little or no activity were clearly indicated. As a result of this work, the compound N,N ′‐[1‐(5,7‐dimethyl‐1,2,4‐triazolo[1,5‐a]pyrimidin‐2‐yl‐thio)butane‐2,3‐di‐imino]bis(2‐chlorobenzenesulfonamide) was selected as showing good activity against a range of species, and will be used as a lead for further development. © 2000 Society of Chemical Industry     

Synthesis and structure–activity relationships of carbohydrazides and 1,3,4‐oxadiazole derivatives bearing an imidazolidine moiety against the yellow fever and dengue vector,Aedes aegypti

BACKGROUND

1,3,4‐Oxadiazole and imidazolidine rings are important heterocyclic compounds exhibiting a variety of biological activities. In this study, novel compounds with oxadiazole and imidazolidine rings were synthesized from 3‐(methylsulfonyl)‐2‐oxoimidazolidine‐1‐carbonyl chloride and screened for insecticidal activities. The proposed structures of the 17 synthesized compounds were confirmed using elemental analysis, infrared (IR), proton nuclear magnetic resonance (¹H‐NMR), and mass spectroscopy.

RESULTS

None of the compounds showed larvicidal activity at the tested concentrations against first‐instar Aedes aegypti larvae. However, nine compounds exhibited promising adulticidal activity, with mortality rates of ≥80% at 5 µg per mosquito. Further dose–response bioassays were undertaken to determine median lethal dose (LD₅₀) values. Compounds 1 , 2b , 2c , 2d , 2 g , 3b , 3c , 3 g, and 3 h were effective, with typical LD₅₀ values of about 5 ? 10 µg per mosquito against female Ae. aegypti. Compounds 2c (bearing a nitro group on the aromatic ring; LD₅₀ = 2.80 ± 0.54 µg per mosquito) and 3 h ( double halogen groups at 2,4 position on the phenyl ring; LD₅₀ = 2.80 ± 0.54 µg per mosquito) were the most promising compounds.

CONCLUSION

Preliminary mode of action studies failed to show consistent evidence of either neurotoxic or mitochondria‐directed effects. Further chemical synthesis within this series may lead to the development of new effective insecticides. © 2017 Society of Chemical Industry

     

Synthesis and structure–activity relationship analysis of bicyclophosphorothionate blockers with selectivity for housefly γ‐aminobutyric acid receptor channels

BACKGROUND: Bicyclophosphorothionates (2,6,7‐trioxa‐1‐phosphabicyclo[2.2.2]octane‐1‐sulfides) are blockers (or non‐competitive antagonists) of γ‐aminobutyric acid (GABA) receptor channels. Twenty‐two bicyclophosphorothionates with different 3‐ and 4‐substituents were synthesised, and [³H]4′‐ethynyl‐4‐n‐propylbicycloorthobenzoate (EBOB) binding assays were performed to evaluate their affinities for housefly and rat GABA receptors. RESULTS: Introduction of an isopropyl group at the 3‐position enhanced the affinity of bicyclophosphorothionates for housefly GABA receptors and reduced the affinity towards rat GABA receptors. The 4‐isopentyl‐3‐isopropylbicyclophosphorothionate showed the highest affinity for housefly GABA receptors (IC₅₀ = 103 nM ) among the analogues tested, while the 4‐cyclohexylbicyclophosphorothionate showed the highest affinity for rat GABA receptors (IC₅₀ = 125 nM ). Among the bicyclophosphorothionates synthesised to date, the former analogue exhibited the highest selectivity for housefly GABA receptors, with an IC₅₀^rat/IC₅₀^fly ratio of approximately 97. Three‐dimensional GABA receptor models successfully explained the structure–activity relationships of the bicyclophosphorothionates. CONCLUSION: The results indicate that minor structural modifications of blockers can change their selectivity for insect versus mammalian GABA receptors. The substituent at the 3‐position of the bicyclophosphorothionates dictates selectivity for housefly versus rat GABA receptors. This information should prove useful for the design of safer insecticides and parasiticides. Copyright © 2010 Society of Chemical Industry