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Neural network-based QSAR and insecticide discovery: spinetoram

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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.

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Abbreviations

ANN:

Artificial neural network

MLR:

Multiple linear regression

SAR:

Structure activity relationships

QSAR:

Quantitative structure activity relationships

UV:

Ultraviolet

ppm:

Parts per million

LC50 :

Lethal concentration resulting in mortality in 50% of the population

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Acknowledgements

We thank Greg Durst (Eli Lilly and Co.), Dr. Anthony Hopfinger (University of New Mexico), and Frank Jenkins, for many enlightening discussions, Dr. Herb Kirst (Eli Lilly and Co.), Larry Creemer (Eli Lilly and Co.) and Dr. Jon Mynderse (Eli Lilly and Co.) for providing some of the compounds, Thomas Worden and Dr. Laura Karr for providing some of the biological data. This research was supported by Dow AgroSciences.

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Author notes

  1. Peter Anzeveno

    Present address: Eli Lilly and Co., Indianapolis, IN, USA

  2. Jacek Martynow

    Present address: Rib-X Pharmaceuticals, Inc., New Haven, CT, USA

Authors and Affiliations

  1. Dow AgroSciences, Discovery Research, 9330 Zionsville Road, Bldg. 306/G1, Indianapolis, IN, 46268, USA

    Thomas C. Sparks, Gary D. Crouse, James E. Dripps, Peter Anzeveno, Jacek Martynow, Carl V. DeAmicis & James Gifford

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  1. Thomas C. Sparks
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  2. Gary D. Crouse
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  3. James E. Dripps
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  4. Peter Anzeveno
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  5. Jacek Martynow
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  6. Carl V. DeAmicis
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  7. James Gifford
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Correspondence to Thomas C. Sparks.

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Sparks, T.C., Crouse, G.D., Dripps, J.E. et al. Neural network-based QSAR and insecticide discovery: spinetoram. J Comput Aided Mol Des 22, 393–401 (2008). https://doi.org/10.1007/s10822-008-9205-8

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  • DOI: https://doi.org/10.1007/s10822-008-9205-8

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