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

• Published in: Bioorganic & medicinal chemistry Vol. 17; no. 22; pp. 6274 - 6279
• Main Authors: Lahm, George P., Stevenson, Thomas M., Selby, Thomas P., Freudenberger, John H., Cordova, Daniel, Flexner, Lindsey, Bellin, Cheryl A., Dubas, Christine M., Smith, Ben K., Hughes, Kenneth A., Hollingshaus, J. Gary, Clark, Christopher E., Benner, Eric A.
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier Ltd 15-11-2007; Elsevier
• Subjects: Animals; Biological and medical sciences; Cell Line; Chemical control; Control; Fundamental and applied biological sciences. Psychology; Humans; Insecticide; Insecticides - chemical synthesis; Insecticides - chemistry; Insecticides - pharmacology; Lepidoptera; Lepidoptera - cytology; Lepidoptera - drug effects; Mice; Molecular Structure; ortho-Aminobenzoates - chemical synthesis; ortho-Aminobenzoates - chemistry; ortho-Aminobenzoates - pharmacology; Phytopathology. Animal pests. Plant and forest protection; Protozoa. Invertebrates; Rats; Receptor; Ryanodine; Ryanodine Receptor Calcium Release Channel - drug effects; Rynaxypyr; Structure-Activity Relationship; Toxicity Tests, Acute; Up-Regulation - drug effects; Ryanodine; Insecticide; Receptor; Rynaxypyr; Agonist; Rat; Toxicity; Insecta; Ryanodine receptor; Amides; Selectivity; Chlorine Organic compounds; Pyrazole derivatives; Bromine Organic compounds; Chemical synthesis; Pesticides; Rodentia; Biological activity; Vertebrata; Mammalia; Arthropoda; Animal; Lepidoptera; Carboxamide; Invertebrata
• ISSN: 0960-894X; 0968-0896; 1464-3405; 1464-3391
• DOI: 10.1016/j.bmcl.2007.09.012

This paper describes the discovery of Rynaxypyr™, the first member from a novel class of anthranilic diamides, with exceptional activity against insects of the order Lepidoptera. Rynaxypyr™ has been found to exhibit its action by release of intracellular Ca
2+ stores mediated by the ryanodine receptor. A comparison of
Heliothis virescens (
Hv) ryanodine receptor activity is made versus insecticidal potency on a series of Lepidoptera, including
Hv. Remarkably high differential receptor selectivity is also demonstrated between insect and mammalian cell lines in support of the low mammalian toxicity.
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.