Salicylate metal-binding isosteres as fragments for metalloenzyme inhibition
Moritz K. Jackl, Hyeonglim Seo, Johannes Karges, Mark Kalaj, Seth M. Cohen
Abstract
). It was observed that salicylate MBIs could maintain or improve enzyme inhibition and selectivity. To probe salicylate MBIs as fragments for fragment-based drug discovery (FBDD), an MBI that showed good inhibitory activity against GLO1 was derivatized and a rudimentary structure-activity relationship was developed. The resulting elaborated fragments showed GLO1 inhibition with low micromolar activity.
Topics & Concepts
ChemistryStereochemistryMetalCombinatorial chemistryOrganic chemistryClick Chemistry and ApplicationsChemical Synthesis and AnalysisMetal complexes synthesis and properties