Synthesis and biological evaluation of N‐acylated tyramine sulfamates containing C–F bonds as steroid sulfatase inhibitors

Steroid sulfatase (STS) is responsible for the hydrolysis of biologically inactive sulfated steroids into their active un‐sulfated forms and promotes the growth of various hormone‐dependent cancers (e.g., breast cancer). Therefore, the STS enzyme is a promising therapeutic target for the treatment of steroid‐sensitive cancers. Herein, we report the synthesis and biological evaluation of sulfamate analogs as potential STS inhibitors based on N‐acylated tyramines that contain C–F bonds. The inhibitory effects of the analogs were tested using STS isolated from human placenta. Of the analogs tested, 4‐(2‐perfluoroundecanoylaminoethyl)‐phenyl sulfamate, 5r, demonstrated the greatest inhibitory effect, with an IC50 value of 2.18 μm (IC50 value of 2.13 μm for coumarin‐7‐O‐sulfamate was used as a reference). These findings were supported by the results our computational analyses performed using molecular docking techniques.