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Discovery of the aryl heterocyclic amine insecticides: synthesis, insecticidal activity, field results, mode of action and bioavailability of a leading field candidate
Author(s) -
Dent William H,
Pobanz Mark A,
Geng Chaoxian,
Sparks Thomas C,
Watson Gerald B,
Letherer Theodore J,
Beavers Kenneth W,
Young Cathy D,
Adelfinskaya Yelena A,
Ross Ronald R,
Whiteker Greg,
Renga James
Publication year - 2017
Publication title -
pest management science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.296
H-Index - 125
eISSN - 1526-4998
pISSN - 1526-498X
DOI - 10.1002/ps.4431
Subject(s) - mode of action , spodoptera , fipronil , trichoplusia , antagonism , biology , aryl , bioavailability , pharmacology , stereochemistry , chemistry , biochemistry , pesticide , receptor , larva , botany , organic chemistry , noctuidae , ecology , alkyl , gene , recombinant dna
BACKGROUND γ ‐Amino butyric acid ( GABA ) antagonists are proven targets for control of lepidopteran and other pests. New heterocyclic compounds with high insecticidal activity were discovered using a competitive‐intelligence‐inspired scaffold‐hopping approach to generate analogs of fipronil, a known GABA antagonist. These novel aryl heterocyclic amines ( AHAs ) displayed broad‐spectrum activity on a number of chewing insect pests. RESULTS Through >370 modifications of the core AHA structure, a 7‐pyrazolopyridine lead molecule was found to exhibit much improved activity on a number of insect pests. In field trial studies, its performance was 2–4 times lower than commercial standards and also appeared to be species dependent, with good activity seen for larvae of Spodoptera exigua , but inactivity on larvae of Trichoplusia ni . CONCLUSION An extensive investigational biology effort demonstrated that these AHA analogs appear to have multiple modes of action, including GABA receptor antagonism and mitopotential or uncoupler activity. The limited capability in larvae of T. ni to convert the lead molecule to its associated open form correlates with the low toxicity of the lead molecule in this species. This work has provided information that could aid investigations of novel GABA antagonists. © 2016 Society of Chemical Industry