title: Neural network-based QSAR and insecticide discovery: spinetoram.
abstract: Improvements in the efficacy and spectrum of the spinosyns, novel fermentation derived insecticide, has long been a goal within Dow AgroSciences. As large and complex fermentation products identifying specific modifications to the spinosyns likely to result in improved activity was a difficult process, since most modifications decreased the activity. A variety of approaches were investigated to identify new synthetic directions for the spinosyn chemistry including several explorations of the quantitative structure activity relationships (QSAR) of spinosyns, which initially were unsuccessful. However, application of artificial neural networks (ANN) to the spinosyn QSAR problem identified new directions for improved activity in the chemistry, which subsequent synthesis and testing confirmed. The ANN-based analogs coupled with other information on substitution effects resulting from spinosyn structure activity relationships lead to the discovery of spinetoram (XDE-175). Launched in late 2007, spinetoram provides both improved efficacy and an expanded spectrum while maintaining the exceptional environmental and toxicological profile already established for the spinosyn chemistry.
authors.affiliation: Dow AgroSciences, Discovery Research, 9330 Zionsville Road, Bldg. 306/G1, Indianapolis, IN, 46268, USA. tcsparks@dow.com
authors.forename: Thomas C
authors.initials: TC
authors.lastname: Sparks
authors.forename: Gary D
authors.initials: GD
authors.lastname: Crouse
authors.forename: James E
authors.initials: JE
authors.lastname: Dripps
authors.forename: Peter
authors.initials: P
authors.lastname: Anzeveno
authors.forename: Jacek
authors.initials: J
authors.lastname: Martynow
authors.forename: Carl V
authors.initials: CV
authors.lastname: Deamicis
authors.forename: James
authors.initials: J
authors.lastname: Gifford
mesh_terms: D000818:Animals; D007306:Insecticides / Q000737:chemistry* / Q000494:pharmacology*; D018942:Macrolides / Q000737:chemistry* / Q000494:pharmacology*; D016571:Neural Networks, Computer; D021281:Quantitative Structure-Activity Relationship
chemical_list: D007306:Insecticides; D018942:Macrolides; C548262:spinetoram