Synthesis of Aryl Propionamide Scaffold Containing a Pentafluorosulfanyl Moiety as SARMs.

The pentafluorosulfane (SF(5)) group, as a more electronegative bioisostere than the trifluoromethyl (CF(3)) group, has been gaining greater attention and increasingly reported usage in medicinal chemistry. Ostarine is the selective androgen receptor modulators (SARMs) containing a CF(3) group in clinical trial III. In this study, 21 ostarine derivatives for replacing the CF(3) group with SF(5) substituents were synthesized. Some SF(5)-derivatives showed androgen receptor (AR) agonistic activities in vitro. The results pointed to the potential of using this scaffold to develop new AR agonists.