Zoltan Benko

SAR studies directed toward the pyridine moiety of the sap-feeding insecticide sulfoxaflor (Isoclast™ active).

Sap-feeding insect pests constitute a major insect pest complex that includes a range of aphids, whiteflies, planthoppers and other insect species. Sulfoxaflor (Isoclast™ active), a new sulfoximine class insecticide, targets sap-feeding insect pests including those resistant to many other classes of insecticides. A structure activity relationship (SAR) investigation of the sulfoximine insecticides revealed the importance of a 3-pyridyl ring and a methyl substituent on the methylene bridge linking the pyridine and the sulfoximine moiety to achieving strong Myzus persicae activity. A more in depth QSAR investigation of pyridine ring substituents revealed a strong correlation with the calculated logoctanol/water partition coefficient (SlogP). Model development resulted in a highly predictive model for a set of 18 sulfoximines including sulfoxaflor. The model is consistent with and helps explain the highly optimized pyridine substitution pattern for sulfoxaflor.

The synthesis and biological activity of 1-alkyl-4-(3-azacyclobenzoyl)-5-hydroxypyrazole herbicides

The benzoylpyrazoles belong to a class of herbicides that inhibit the enzyme 4-hydroxyphenylpyruvate dioxygenase (HPPD). This mode of action is characterized by bleaching due to the disruption of plastoquinone and α-tocopherol biosynthesis. Early studies indicated that the C(3) position of benzoylpyrazoles can accommodate a wide range of functionality. This paper describes synthetic efforts to improve cool season grass weed activity and wheat selectivity by incorporating cyclic moieties attached through nitrogen at this position. The aza substituents were generally installed by nucleophilic aromatic substitution, however, an efficient four-step method was developed for constructing substituted morpholino moieties directly on pre-formed benzoylpyrazoles. The structure-activity relationships revealed that certain piperidino moieties provided good activity on wild oat, while exhibiting selectivity toward wheat. They also showed that excellent levels of activity on wild oat and blackgrass can be achieved with morpholino substituents.

Studies toward understanding the SAR around the sulfoximine moiety of the sap-feeding insecticide sulfoxaflor.

BACKGROUND The discovery of sulfoxaflor (Isoclast™ active) stemmed from a novel scaffold-based approach toward identifying bioactive molecules. It exhibits broad-spectrum control of many sap-feeding insect pests, including aphids, whiteflies, hoppers and Lygus. Systematic modifications of the substituents flanking each side of the sulfoximine moiety were carried out to determine whether these changes would improve potency. RESULTS Structure-activity relationship (SAR) studies showed that, with respect to the methylene linker, both mono- and disubstitution with alkyl groups of varying sizes as well as cyclic analogs exhibited excellent control of cotton aphids. However, against green peach aphids a decrease in activity was observed with substituents larger than ethyl as well as larger cycloalkyl groups. At the terminal tail there appeared to be a narrow steric tolerance as well, with linear groups or small rings more active against green peach aphids than bulkier groups. CONCLUSION A novel series of compounds exploring the substituents flanking the sulfoximine moiety of sulfoxaflor were prepared and tested for bioactivity against cotton aphids and green peach aphids. SAR studies indicated that a decrease in green peach aphid potency was observed at the methylene linker as well as at the terminal tail with bulkier substituents. A quantitative structure-activity relationship analysis of the compounds revealed significant correlation of activity with two molecular descriptors, vol (volume of a molecule) and GCUT_SMR_3 (molar refractivity). This predictive model helps to explain the observed activity with the various substituents.