2. Academic Validation
  3. Bioisosteric-Replacement-Driven Lead Optimization of Tyclopyrazoflor

Bioisosteric-Replacement-Driven Lead Optimization of Tyclopyrazoflor

  • J Agric Food Chem. 2022 Sep 14;70(36):11123-11137. doi: 10.1021/acs.jafc.2c00654.
Meijun Chen 1,  Zhong Li 1 2,  Xusheng Shao 1 2 3 4,  Peter Maienfisch 1 5
Affiliations

Affiliations

  • 1 Shanghai Key Laboratory of Chemical Biology, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, People's Republic of China.
  • 2 State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai 200237, People's Republic of China.
  • 3 Shanghai Frontier Science Research Base of Optogenetic Techniques for Cell Metabolism, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, People's Republic of China.
  • 4 Engineering Research Center of Pharmaceutical Process Chemistry, Ministry of Education, School of Pharmacy, East China University of Science and Technology, Shanghai 200237, People's Republic of China.
  • 5 CreInSol Consulting & Biocontrols, CH-4118 Rodersdorf, Switzerland.
PMID: 35561416 DOI: 10.1021/acs.jafc.2c00654
Abstract

A heterocyclic replacement strategy has been applied attempting to further optimize the biological properties of the new Insecticide tyclopyrazoflor, a pyridinyl-pyrazole compound with excellent activity against sap-feeding insects recently discovered by Corteva. Our research program on this novel chemical class of Insecticide was targeted to evaluate the importance of both the pyridyl and pyrazole moieties on the biological activity, properties, and structure-activity. Synthetic methodologies have been developed delivering our designed target compounds in moderate to good yields. In our attempt to rationalize the biological activity differences of tyclopyrazoflor analogues, a potential surface analysis based on a density functional theory (DFT) calculation and DFT-derived Multiwfn and VMD program model was performed. Furthermore, the SwissBioisostere online database was applied as a great source for inspiration for bioisosteric replacements.

Keywords

SwissBioisostere; bioisosteric replacement; density functional theory (DFT); pyridazine; tyclopyrazoflor.

Figures
Products