Daniel Cordova

FMC Corporation | FMC

In recent years, the registrations for a number of commercial insecticides utilized for piercing/sucking insects have been cancelled or restricted. To meet this growing need for new hemipteran controlling agrochemicals, we discovered a 2‐(pyridin‐3‐yl)‐thiazole compound, with limited insecticidal activity against cotton/melon aphid (Aphis gossypii)...

BACKGROUND Insects of the order Lepidoptera are among the most destructive global pests, causing billions of dollars in damage annually. A new class of N‐arylpyrazole‐4‐methylpiperidines with potent activity on lepidopteran species has been discovered. RESULTS In a high‐throughput insecticide screen compound 1 was identified to possess modest acti...

The ryanodine receptor (RyR) is an intracellular calcium channel critical to the regulation of insect muscle contraction and the target site of diamide insecticides such as chlorantraniliprole, cyantraniliprole and flubendiamide. To-date, diamides are the only known class of synthetic molecules with high potency against insect RyRs. Target-based sc...

We have discovered mesoionic pyrido[1,2-a]pyrimidinones as a novel class of insecticides and identified compounds such as dicloromezotiaz for development. During optimization of this area, we also discovered that mesoionic pyrido[1,2-a]pyrimidinones containing 3-biaryl groups at the 3-position of the core ring possess potent biological activity aga...

Insecticide resistance has been and continues to be a significant problem for invertebrate pest control. As such, effective insecticide resistance management (IRM) is critical to maintain the efficacy of current and future insecticides. A technical group within CropLife International, the Insecticide Resistance Action Committee (IRAC) was establish...

The discovery and optimization of a new class of naphthalene isoxazolines led to the identification of afoxolaner as a new ectoparasiticide with excellent effectiveness against fleas and ticks by both topical and oral treatments. The compound is shown to work by inhibition of the GABA‐gated chloride channel with no observed cyclodiene cross‐resista...

Pyraxalt™ (DPX-RAB55; Triflumezopyrim), a molecule developed by DuPont™ Crop Protection, provides excellent control of rice plant hoppers i.e. Nilaparvata lugens, Sogatella furcifera, Laodelphax striatellus and leaf hoppers; Nephotettix cincticeps and N. virescens. Pyraxalt™ has been observed to be effective against populations found to be resistan...

Fluazaindolizine is a new highly effective and selective product for the control of plant parasitic nematodes. Specificity for nematodes coupled with absence of activity against the target sites of commercial nematicides suggests that fluazaindolizine has a novel mode of action. The discovery, structure-activity development and biological propertie...

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...

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...

Background: As the world population grows toward 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 due to pests. Development of new insecticides will help sustain this prote...

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, a...

Triflumezopyrim is an extremely effective hopper insecticide with low impact on non-target organisms including pollinators. This unique class of mesoionic chemistry targets the nicotinic acetylcholine receptor , inducing a physiological action which is distinct from that of neonicotinoids. The discovery, synthesis, optimization and mode of action w...

A novel class of synthetic tubulin polymerization disruptors, based on a substituted pyrazin-2-one core, has been discovered. These molecules have proven to be potent broad spectrum fungicides, with activity on agriculturally important ascomycete and basidiomycete pathogens. They have also been found to be particularly potent against human rhabdomy...

Afoxolaner is an isoxazoline compound characterized by a good safety profile and extended effectiveness against fleas and ticks on dogs following a single oral administration. In vitro membrane feeding assay data and in vivo pharmacokinetic studies in dogs established an afoxolaner blood concentration of 0.1–0.2 μg/ml to be effective against both f...

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-a...

The genes encoding ryanodine receptor homologs have been characterized from multiple insect families. The genes and their corresponding polypeptides have a number of uses including but not limited to the development of screens to identify insecticidally active compounds. Methods are outlined for overcoming toxic effects of expressing recombinant pr...

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...

Anthranilic diamides, which include the new commercial insecticide, chlorantraniliprole, are an exciting new class of chemistry that target insect ryanodine receptors. These receptors regulate release of stored intracellular calcium and play a critical role in muscle contraction. As with insects, nematodes express ryanodine receptors and are sensit...

Isoxazoline insecticides have been shown to be potent blockers of insect GABA receptors with excellent activity on a broad pest range, including Lepidoptera and Hemiptera. Herein we report on the synthesis, biological activity and mode-of-action for a class of 4-heterocyclic aryl isoxazoline insecticides.

Ryanodine Receptor Modulators: DiamidesFlubendiamideAnthranilic Diamide Insecticides: Chlorantraniliprole and CyantraniliproleReferences

The Insecticide Resistance Action Committee (IRAC) is a Specialist Technical Group of CropLife International that is focused on ensuring the long term efficacy of insect control products through effective resistance management. A key component is the Mode of Action (MoA) classification scheme, which serves as a basis for constructing appropriate In...

The Insecticide Resistance Action Committee (IRAC) is a Specialist Technical Group of CropLife International that is focused on ensuring the long term efficacy of insect control products through effective resistance management. A key component is the Mode of Action (MoA) classification scheme, which serves as a basis for constructing appropriate In...

The discovery of new pesticides that are highly effective against target pests, work by new modes of action to aid in resistance management, and meet societal demands for safety to humans and the environment, requires a new and different approach than historical processes which have focused primarily on efficacy. In an effort to meet these demands...

Diamide insecticides have emerged as one of the most promising new classes of insecticide chemistry owing to their excellent insecticidal efficacy and high margins of mammalian safety. Chlorantraniliprole and flubendiamide, the first two insecticides from this class, demonstrate exceptional activity across a broad range of pests in the order Lepido...

Ryanodine receptors (RyRs) are a distinct class of ligand-gated calcium channels controlling the release of calcium from intracellular stores. They are located on the sarcoplasmic reticulum of muscle and the endoplasmic reticulum of neurons and many other cell types. Ryanodine, a plant alkaloid and an important ligand used to characterize and purif...

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...

IntroductionDiscovery of the Anthranilic Diamide InsecticidesDiscovery of RynaxypyrTMBiological AttributesToxicologyMechanism of ActionConclusion DedicationReferences

Development of insecticides with unique modes of action is necessary to combat resistance. DuPont Crop Protection has discovered a new class of insecticides which provides exceptional control through action on a novel target, the ryanodine receptor. Studies on native and recombinant insect ryanodine receptors demonstrate that the anthranilic diamid...

Development of insecticides with unique modes of action is necessary to combat widespread insecticide resistance. A new class of insecticides has been discovered, the anthranilic diamides, that provides exceptional control through action on a novel target, the ryanodine receptor. Anthranilic diamides potently activate this receptor, releasing store...

A novel class of anthranilic diamides has been discovered with exceptional insecticidal activity on a range of Lepidoptera. These compounds have been found to exhibit their action by release of intracellular Ca2+ stores mediated by the ryanodine receptor. The discovery, synthesis, structure-activity, and biological results are presented.

A muscarinic acetylcholine receptor (mAChR), DM1, expressed in the nervous system of Drosophila melanogaster, has been stably expressed in a Drosophila S2 cell line (S2-DM1) and used to investigate spatiotemporal calcium changes following agonist activation. Carbamylcholine (CCh) and oxotremorine are potent agonists, whereas application of the vert...

Piperovatine, a sialogogic, piscicidal, and buccal local anesthesia producing isobutyl amide from the amazonian piscicidal and toothache-relieving plant, Piper piscatorum Trelease et Yuncker (Piperaceae), was evaluated for its ability to induce changes in neuronal intracellular calcium concentration. Ratiometric calcium imaging of Periplaneta ameri...

The radiolabelled bicyclic dinitrile, [ ³ H]‐3,3‐bis‐trifluoromethyl‐bicyclo[2.2.1]heptane‐2,2‐dicarbonitrile ([ ³ H]‐BIDN), exhibited, specific binding of high affinity to membranes of the southern corn rootworm ( Diabrotica undecimpunctata howardi ) and other insects. A variety of γ‐aminobutyric acid (GABA) receptor convulsants, including the ins...

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 th...