Nortropinyl-Arylsulfonylureas as novel, reversible inhibitors of human steroid sulfatase

Abstract Steroid sulfatase (STS) has emerged as an attractive target for a range of estrogen- and androgen-dependent diseases. Searching for novel chemotypes as STS inhibitors, we identified nortropinyl-arylsulfonylurea 3 as a hit from high-throughput screening. A series of analogues was prepared in order to explore the essential structural elements for STS inhibition, and first structure–activity relationships were established. Mechanistic investigations revealed that the compounds are reversible, competitive inhibitors of STS.