title: N-Acyl arylsulfonamides as novel, reversible inhibitors of human steroid sulfatase.
abstract: Steroid sulfatase (STS) is an attractive target for a range of oestrogen- and androgen-dependent diseases. In search of novel chemotypes of STS inhibitors, we had previously identified nortropinyl-arylsulfonylureas 1; however, while these compounds were good inhibitors of purified STS (lowest K(i)=76 nM), they showed only weak inhibition of STS activity in cells (lowest IC(50) around 2 microM). Extended structure-activity relationship studies involving modification of the phenylacetyl side chain and replacement of the nortropine element by simpler scaffolds led to the discovery of N-acyl arylsulfonamides, more specifically N-(Boc-piperidine-4-carbonyl)-benzenesulfonamides, as STS inhibitors, some of which exhibit improved cellular potency (best IC(50)=270 nM).
authors.affiliation: Novartis Institutes for BioMedical Research, Brunnerstrasse 59, A-1235 Vienna, Austria.
authors.forename: Philipp
authors.initials: P
authors.lastname: Lehr
authors.forename: Andreas
authors.initials: A
authors.lastname: Billich
authors.forename: Barbara
authors.initials: B
authors.lastname: Wolff
authors.forename: Peter
authors.initials: P
authors.lastname: Nussbaumer
mesh_terms: D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D020128:Inhibitory Concentration 50; D043266:Steryl-Sulfatase / Q000037:antagonists & inhibitors* / Q000235:genetics; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000138:chemical synthesis* / Q000494:pharmacology; D014162:Transfection
chemical_list: D004791:Enzyme Inhibitors; D013449:Sulfonamides; D043266:Steryl-Sulfatase