More than an Amide Bioisostere: Discovery of 1,2,4-Triazole-containing Pyrazolo[1,5- <i>a</i> ]pyrimidine Host CSNK2 Inhibitors for Combatting β-Coronavirus Replication
Han Wee Ong, Xuan Yang, Jeffery L. Smith, Rebekah J. Dickmander, Jason W. Brown, Tammy M. Havener, Sharon Taft-Benz, Stefanie Howell, Marcia K. Sanders, Jacob L. Capener, Rafael M. Couñago, Edcon Chang, Andreas Krämer, Nathaniel J. Moorman, Mark T. Heise, Alison D. Axtman, David H. Drewry, Timothy M. Willson
Abstract
in vivo was observed and may be attributed to lung accumulation, although in vivo pharmacological effect was not observed. Further optimization of this novel chemotype may validate CSNK2 as an antiviral target in vivo.
Topics & Concepts
ChemistryPyrimidineIn vivoBioisostereAmideTriazoleDrug discoveryPotencyLead compoundHydrogen bondStereochemistryPyrimidine metabolismCombinatorial chemistryIn vitroBiochemistryChemical synthesisEnzymeMoleculeOrganic chemistryPurineBiologyBiotechnologyinterferon and immune responsesViral Infections and Immunology ResearchSARS-CoV-2 and COVID-19 Research