CF₃-Cyclobutanes: Synthesis, Properties, and Evaluation as a Unique <i>tert</i>-Butyl Group Analogue.

ABSTRACT: Isosteric replacement of functional groups is an emerging strategy for optimizing bioactive molecules in drug discovery. tert-Butyl group is a particularly important moiety, yet its isosteric replacement with 1-trifluoromethyl-cyclobutyl group has been rather neglected. To enable the advance of this molecular fragment in drug discovery programs, we report the synthesis of over 30 small-molecule building blocks featuring the trifluoromethyl-cyclobutyl fragment, achieved by reacting sulfur tetrafluoride with cyclobutylcarboxylic acids on a gram-to-multigram scale. Furthermore, we characterized the structural properties of this group through X-ray analysis, studied its effect on acid-base transitions, and evaluated its Hammett parameters. Finally, we evaluated the replacement of ter

SUBMITTER: Ahunovych V 

PROVIDER: S-EPMC11600199 | biostudies-literature | 2024 Nov

REPOSITORIES: biostudies-literature