Applying a Bioisosteric Replacement Strategy in the Discovery and Optimization of Mesoionic Pyrido[1,2-<i>a</i>]pyrimidinone Insecticides: A Review
Wenming Zhang, George P. Lahm, Thomas F. Pahutski, Kenneth A. Hughes
Abstract
-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. Through exploring various substituents at the 1 position, evaluating a variety of mesoionic bicyclic ring scaffolds, and examining substituents on the phenyl group at the 3 position of the mesoionic core as well as substituents on the mesoionic ring skeleton, many compounds were discovered with excellent hopper activity or potent activity against a wide range of Lepidoptera. Ultimately, dicloromezotiaz was identified for commercial development to control a broad spectrum of lepidopteran pests.