Application of the Pentafluorosulfanyl Group as a Bioisosteric Replacement.

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 SF group, yet efforts to integrate this group into lead optimization continue unabated. Typically, the SF group has been used as a replacement for trifluoromethyl, tert-butyl, halogen, or nitro groups. In this review, the use of the SF 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 SF -substituted molecules.

© 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.