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

• Published in: Bioorganic & medicinal chemistry letters 2013-12, Vol.23 (23), p.6341-6345
• Main Authors: Selby, Thomas P., Lahm, George P., Stevenson, Thomas M., Hughes, Kenneth A., Cordova, Daniel, Annan, I. Billy, Barry, James D., Benner, Eric A., Currie, Martin J., Pahutski, Thomas F.
• Format: Article
• Language: English
• Subjects: Animals; Anthranilic diamides; Aphids; application rate; Calcium; Calcium channels; Calcium Channels - chemistry; chemistry; Chlorantraniliprole; commercialization; Cyantraniliprole; insect control; insect pests; insecticidal properties; Insecticides - chemical synthesis; Insecticides - chemistry; Lepidoptera; Molecular Structure; mortality; myocytes; ortho-Aminobenzoates - chemical synthesis; ortho-Aminobenzoates - chemistry; Pyrazoles - chemical synthesis; Pyrazoles - chemistry; Ryanodine receptor; Ryanodine Receptor Calcium Release Channel - chemistry; Ryanodine Receptor Calcium Release Channel - metabolism; ryanodine receptors; Structure-Activity Relationship
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2013.09.076

This Letter describes the chemistry and structure–activity trends for a series of cyanoanthranilic diamides that exhibit their insecticidal action by release of intracellular Ca2+ stores mediated by the ryanodine receptor. From this work, cyantraniliprole was selected for commercial development. 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. Here we report on the chemistry, biology and structure–activity trends for a series of cyanoanthranilic diamides from which cyantraniliprole was selected for commercial development.