Applying a Bioisosteric Replacement Strategy in the Discovery and Optimization of Mesoionic Pyrido[1,2-]pyrimidinone Insecticides: A Review.

Mesoionic pyrido[1,2-]pyrimidinones are a unique class of heterocyclic compounds. Compounds from this class with a -propyl group substituted at the 1 position of the mesoionic core were discovered with interesting insecticidal activity in our screen. In this overview, we showcase how a bioisosteric replacement strategy was applied during the discovery and optimization of this class of compounds.

Mesoionic pyrido[1,2-a]pyrimidinones: Discovery of dicloromezotiaz as a lepidoptera insecticide acting on nicotinic acetylcholine receptors.

A novel class of mesoionic pyrido[1,2-a]pyrimidinones has been discovered with exceptional insecticidal activity controlling a number of insect species. In this communication, we report the part of the optimization program that led to the identification of dicloromezotiaz as a potent insecticide to control a broad range of lepidoptera. Our efforts in discovery, synthesis, structure-activity relationship elucidation, and biological activity evaluation are also presented.

Mesoionic insecticides: a novel class of insecticides that modulate nicotinic acetylcholine receptors.

Background: As the world population grows towards 9 billion by 2050, it is projected that food production will need to increase by 60%. A critical part of this growth includes the safe and effective use of insecticides to reduce the estimated 20-49% loss of global crop yields owing to pests. The development of new insecticides will help to sustain this protection and overcome insecticide resistance.

Mesoionic pyrido[1,2-a]pyrimidinones: Discovery of triflumezopyrim as a potent hopper insecticide.

A novel class of mesoionic pyrido[1,2-a]pyrimidinones has been discovered with exceptional insecticidal activity controlling a number of insect species. In this communication, we report the part of the optimization program which led to the discovery of triflumezopyrim as a highly potent insecticide controlling various hopper species. Our efforts in discovery, synthesis, structure-activity relationship elucidation, and biological activity evaluation are also presented.

Mesoionic pyrido[1,2-a]pyrimidinones: A novel class of insecticides inhibiting nicotinic acetylcholine receptors.

A novel class of mesoionic pyrido[1,2-a]pyrimidinones has been discovered with exceptional insecticidal activity controlling a number of insect species, particularly hemiptera and lepidoptera. Mode-of-action studies showed that they act on nicotinic acetylcholine receptors (nAChRs) primarily as inhibitors. Here we report the discovery, evolution, and preparation of this class of chemistry.

Discovery, synthesis, and evaluation of N-substituted amino-2(5H)-oxazolones as novel insecticides activating nicotinic acetylcholine receptors.

N-Substituted amino-2(5H)-oxazolones A are a novel class of insecticides acting as nicotinic acetylcholine receptor (nAChR) agonists and show potent activity against hemipteran insect species. Here we report the discovery and preparation of this class of chemistry. Our efforts in SAR elucidation, biological activity evaluation, as well as mode-of-action studies are also presented.

Discovery of cyantraniliprole, a potent and selective anthranilic diamide ryanodine receptor activator with cross-spectrum insecticidal activity.

Anthranilic diamides are an exceptionally active class of insect control chemistry that selectively activates insect ryanodine receptors causing mortality from uncontrolled release of calcium ion stores in muscle cells. Work in this area led to the successful commercialization of chlorantraniliprole for control of Lepidoptera and other insect pests at very low application rates. In search of lower logP analogs with improved plant systemic properties, exploration of cyano-substituted anthranilic diamides culminated in the discovery of a second product candidate, cyantraniliprole, having excellent activity against a wide range of pests from multiple insect orders.

Synthetic atpenin analogs: Potent mitochondrial inhibitors of mammalian and fungal succinate-ubiquinone oxidoreductase.

Atpenins and harzianopyridone represent a unique class of penta-substituted pyridine-based natural products that are potent inhibitors of complex II (succinate-ubiquinone oxidoreductase) in the mitochondrial respiratory chain. These compounds block electron transfer in oxidative phosphorylation by inhibiting oxidation of succinate to fumarate and the coupled reduction of ubiquinone to ubiquinol. From our investigations of complex II inhibitors as potential agricultural fungicides, we report here on the synthesis and complex II inhibition for a series of synthetic atpenin analogs against both mammalian and fungal forms of the enzyme.

Rynaxypyr: a new insecticidal anthranilic diamide that acts as a potent and selective ryanodine receptor activator.

Rynaxypyr is a highly potent and selective activator of insect ryanodine receptors with exceptional activity on a broad range of Lepidoptera. A strong correlation between insecticidal activity and ryanodine receptor activation is observed along with selective activity against insect over mammalian receptors. The synthesis and biological results are presented.