LAUSR

We recently presented Stafia‐1 as the first chemical entity that inhibits the transcription factor STAT5a with selectivity over the highly homologous STAT5b. Stafia‐1, which was identified from a series of symmetrically substituted m‐terphenyl phosphates, binds to the interface between the SH2 domain and the linker domain of STAT5a. Here, we outline a synthetic strategy for the synthesis of asymmetrically substituted m‐terphenyl phosphates, which can be tailored to address their asymmetric STAT5a binding site in a more specific manner. The asymmetrically substituted m‐terphenyl phosphate with the highest activity against STAT5a was converted to a phosphatase‐stable monofluoromethylene phosphonate. The synthetic methodology and activity analysis described here provide first insights into the structure‐activity relationships of m‐terphenyl phosphates for use as selective STAT5a inhibitors.