In the present work, we report convenient methods for the synthesis and biological evaluation of N-phosphorylated derivatives of 3-(4-aminophenyl)-coumarin-7-O-sulfamate as potential steroid sulfatase (STS) inhibitors. Their binding modes were modeled using docking techniques. The inhibitory effects of the synthesized compounds were tested on STS isolated from human placenta. All of the newly synthesised coumarin derivatives were powerful inhibitors of STS with IC₅₀ values ranging between 0.19 and 0.78 μM. In particular, we found that 3-[4-(diphenoxy-phosphorylamino)-phenyl]-coumarin-7-O-sulfamate 10e and 3-[4-(dibenzyloxy-phosphorylamino)-phenyl]-coumarin-7-O-sulfamate 10f produced the highest inhibitory effects, with IC₅₀ values of 0.19 and 0.24 μM, respectively (IC₅₀ values of 1.38 μM for coumarin-7-O-sulfamate 2 and 1.03 μM for coumate 3 used as reference). The structure–activity relationships of the synthesized coumarin derivatives toward the STS enzyme were discussed.