title: 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.
authors.affiliation: Novartis Research Institute Vienna, Brunnerstrasse 59, A-1235 Vienna, Austria. peter.nussbaumer@pharma.novartis.com
authors.forename: Peter
authors.initials: P
authors.lastname: Nussbaumer
authors.forename: Dieter
authors.initials: D
authors.lastname: Geyl
authors.forename: Amarylla
authors.initials: A
authors.lastname: Horvath
authors.forename: Philipp
authors.initials: P
authors.lastname: Lehr
authors.forename: Barbara
authors.initials: B
authors.lastname: Wolff
authors.forename: Andreas
authors.initials: A
authors.lastname: Billich
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D015195:Drug Design; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000494:pharmacology*; D006801:Humans; D007202:Indicators and Reagents; D007700:Kinetics; D043266:Steryl-Sulfatase / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship; D013453:Sulfonylurea Compounds / Q000138:chemical synthesis* / Q000494:pharmacology*
chemical_list: D004791:Enzyme Inhibitors; D007202:Indicators and Reagents; D013453:Sulfonylurea Compounds; D043266:Steryl-Sulfatase