Solid-phase synthesis and biological evaluation of piperazine-based novel bacterial topoisomerase inhibitors.
Basic Information
ID: ALA5131416
Journal: Bioorg Med Chem Lett
Title: Solid-phase synthesis and biological evaluation of piperazine-based novel bacterial topoisomerase inhibitors.
Authors: Flagstad T, Pedersen MT, Jakobsen TH, Felding J, Tolker-Nielsen T, Givskov M, Qvortrup K, Nielsen TE.
Abstract: There is an emerging global need for new and more effective antibiotics against multi-resistant bacteria. This situation has led to massive industrial investigations on novel bacterial topoisomerase inhibitors (NBTIs) that target the vital bacterial enzymes DNA gyrase and topoisomerase IV. However, several of the NBTI compound classes have been associated with inhibition of the hERG potassium channel, an undesired cause of cardiac arrhythmia, which challenges medicinal chemistry efforts through lengthy synthetic routes. We herein present a solid-phase strategy that rapidly facilitates the chemical synthesis of a promising new class of NBTIs. A proof-of-concept library was synthesized with the ability to modulate both hERG affinity and antibacterial activity through scaffold substitutions.
CiteXplore: 34906671
DOI: 10.1016/j.bmcl.2021.128499
Patent ID: ┄