Applying a Bioisosteric Replacement Strategy in the Discovery and Optimization of Mesoionic Pyrido[1,2-a]pyrimidinone
Wenming Zhang1, George P Lahm1, Thomas F Pahutski1
1Stine Research Center, FMC Ag Solutions, 1090 Elkton Road, Newark, Delaware 19711, United States.
Journal of Agricultural and Food Chemistry
|April 8, 2022
Summary
Researchers discovered novel insecticidal compounds derived from mesoionic pyrido[1,2-a]pyrimidinones. Optimization led to dicloromezotiaz, an effective agent against various lepidopteran pests.
Area of Science:
- Agrochemical Science
- Medicinal Chemistry
- Organic Synthesis
Background:
- Mesoionic pyrido[1,2-a]pyrimidinones represent a unique heterocyclic scaffold.
- Initial screening identified compounds with insecticidal properties, particularly those with an n-propyl group at the 1-position.
Purpose of the Study:
- To explore the structure-activity relationships of mesoionic pyrido[1,2-a]pyrimidinones for insecticidal applications.
- To discover and optimize novel insecticidal agents through bioisosteric replacement strategies.
Main Methods:
- Systematic exploration of substituents at the 1-position of the mesoionic core.
- Evaluation of diverse mesoionic bicyclic ring scaffolds.
- Modification of substituents on the phenyl group at the 3-position and the mesoionic ring skeleton.
Main Results:
- Discovery of numerous compounds exhibiting significant hopper activity.
- Identification of potent insecticides effective against a broad range of Lepidoptera.
- Dicloromezotiaz emerged as a lead candidate for commercial development.
Conclusions:
- Bioisosteric replacement is a viable strategy for discovering potent insecticides within this chemical class.
- The optimized compounds demonstrate broad-spectrum efficacy against key agricultural pests.
- Dicloromezotiaz shows promise for controlling lepidopteran pests in agriculture.
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