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Polycyclic dinitriles: a novel class of potent GABAergic insecticides provides a new radioligand, [3H]BIDN

  • Articles from the ICINN 97 Conference
  • National Design of Drugs and Insecticides
  • Published:
Invertebrate Neuroscience

Abstract

The polycyclic dinitriles are a potent class of insecticides which are non-competitive GABA (γ-aminobutyric a acid) antagonists acting at the convulsant site. Comparison with other classes of GABA convulsant site ligands using molecular modelling has shown significant structural similarities. We have developed a pharmacophore model which unifies this class and some previous classes of GABA convulsants. Key pharmacophore elements are a polarizable functionality separated by a fixed distance from two H-bond accepting elements. This model is based on information from X-ray crystal structures and Sybyl using the Tripos force field. Using this pharmacophore model, numerous structural modifications were explored to enhance understanding of structure-activity relationships at the GABA receptor convulsant site of insects and mammals. A radiolabelled bicyclic dinitrile, [3H]BIDN ([3H]3,3-bis-trifluoromethyl-bicyclo[2,2,1] heptane-2,2-dicarbonitrile), was prepared from this area of chemistry and was used as a probe for the interaction of polycyclic dinitriles at the target site.

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Authors and Affiliations

  1. DuPont Agricultural Products, Elkton Road, P.O. Box 30, 19714-0030, Newark, DE, USA

    James J. Rauh, Caleb W. Holyoke, Daniel A. Kleier, James K. Presnail, Eric A. Benner, Daniel Cordova & Michael H. Howard

  2. The Babraham Institute Laboratory of Molecular Signalling, P.O. Box 158, CB2 3EJ, Cambridge, UK

    Alastair M. Hosie, Steven D. Buckingham, Howard A. Baylis & David B. Sattelle

Authors
  1. James J. Rauh
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  2. Caleb W. Holyoke
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  3. Daniel A. Kleier
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  4. James K. Presnail
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  5. Eric A. Benner
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  6. Daniel Cordova
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  7. Michael H. Howard
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  8. Alastair M. Hosie
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  9. Steven D. Buckingham
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  10. Howard A. Baylis
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  11. David B. Sattelle
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Correspondence to James J. Rauh.

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Rauh, J.J., Holyoke, C.W., Kleier, D.A. et al. Polycyclic dinitriles: a novel class of potent GABAergic insecticides provides a new radioligand, [3H]BIDN. Invertebrate Neuroscience 3, 261 (1997). https://doi.org/10.1007/BF02480383

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