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5‐Membered Mesoionic Insecticides: Synthesis and Evaluation of 1,3,4‐Thiadiazol‐4‐ium‐2‐olates with High Affinity for the Insect Nicotinic Acetylcholine Receptor
Author(s) -
Kuzmina Olesya M.,
Weisel Martin,
Narine Arun A.
Publication year - 2019
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201900637
Subject(s) - mesoionic , chemistry , nicotinic agonist , acetylcholine receptor , nicotinic acetylcholine receptor , ring (chemistry) , in vitro , annulation , insect , in vivo , stereochemistry , combinatorial chemistry , receptor , biochemistry , organic chemistry , microbiology and biotechnology , botany , biology , catalysis
The vast majority of drugs and agrochemicals contain heterocyclic ring systems, which impact ease of synthesis, speed of compound derivatization, and protein target site binding, as well as uptake, transport and many other properties. Mesoionics are unique compact heterocyclic structures with an aromatic and highly polarized character. The design and synthesis of 5‐membered mesoionic thiadiazol‐4‐ium‐2‐olates with high insecticidal activity and potent in vitro affinity on insect nicotinic acetylcholine receptors (nAChRs) is described. Modelling experiments using a known acetylcholine‐binding protein as surrogate for the insect nAChR showed interactions with the thiadiazoliumolate that were consistent with that expected for related insecticides. Quantum chemical, photostability, greenhouse residual, as well as plant systemicity studies were conducted to understand the in vitro and in vivo behavior of this novel class of insecticides.