Application of the Pentafluorosulfanyl Group as a Bioisosteric Replacement

Abstract

The success of fluorinated molecules in drug design has led medicinal chemists to search for new fluorine-containing substituents. A major recently developed group is the pentafluorosulfanyl group. This group is stable under physiological conditions and displays unique physical and chemical properties. There are currently few synthetic methods to install the SF₅ group, yet efforts to integrate this group into lead optimization continue unabated. Typically, the SF₅ group has been used as a replacement for trifluoromethyl, tert-butyl, halogen, or nitro groups. In this review, the use of the SF₅ group as a bioisosteric replacement for each of these three functionalities is compared and contrasted across various groups of biologically active molecules. The organization and presentation of these data should be instructive to medicinal chemists considering to design synthetic strategies to access SF₅ -substituted molecules.

Keywords: bioisosteres; drug design; fluorine; nitro groups; sulfur.