C. Gnamm et al. / Bioorg. Med. Chem. Lett. 22 (2012) 3800–3806
3805
The new diamides presented here were tested against a selec-
tion of phytophagous insects which cause damage in different cul-
tures of high commercial relevance, such as lepidopteran chewing
pests (Spodoptera littoralis (Egyptian cotton leafworm), Heliothis
virescens (tobacco budworm) and Plutella xylostella (diamondback
moth)), hemipteran sucking pests (Myzus persicae (green peach
aphid), Thrips tabaci (onion thrips) or coleopteran pest (Diabrotica
virgifera (western corn rootworm)).
in the nM range for some analogues. Seed treatment trials con-
ducted under field conditions demonstrated the excellent soil
movement and plant systemicity of some analogues.
Acknowledgments
We would like to thank D. Ost and B. Frid, for their skillful work
in the chemistry lab, P. Cutler and M. Blacker for generating in vitro
data, A. Pierce for generating physical data, and K. Gaus and M. M.
Stempien for the measurement of the NMR spectra and helpful dis-
cussions. Also acknowledged is Professor C. Bolm (RWTH Aachen
University) for fruitful discussions.
The intrinsic activity of these compounds as modulators of the
insect ryanodine receptors was quantified in two binding assays
developed in a lepidopteran (S. littoralis) and a hemipteran species
(M. persicae, Table 1; for a description of the assay, see the Supple-
mentary data). The best sulfoximine and sulfonimidamide deriva-
tives displaced the tritiated derivative 44 with IC50 values of 3–
10 nM, comparable to the best compounds of the diamide class.
Selected results from greenhouse tests and binding assays as
well as selected physical properties are summarized in Table 1.
The high aqueous solubilities observed for the sulfoximines are
not always well reflected by the logP values, which may be due
to crystal packing effects.29 Remarkable greenhouse activity
against lepidopteran pests and interesting activity against aphids
was observed for sulfoximine analogues (entries 1–5) as compared
to diamide standards (entries 12–14). Interesting activity against
corn rootworm and thrips was also detected for some analogues
(data not shown). The interesting Myzus activity of some of the sul-
foximines (entries 2, 3 and 5) may be explained by a better bio-
availability profile (high aqueous solubility and relatively low
logP), as compared to standards 2 and 1 (entries 12 and 14). Re-
duced activity of 25f and 47 (entries 1 and 4) against Myzus is more
difficult to rationalize.
Supplementary data
Supplementary data associated with this article can be
References and notes
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Figure 5. Seed treatment field trials with 25f and 45 (Table 1, entries 1 and 2). Seed
loading is 1 mg AI/seed. DAP: day after planting.