N-Acyl arylsulfonamides as novel, reversible inhibitors of human steroid sulfatase
| Autor: | Andreas Billich, Philipp Lehr, Barbara Wolff, Peter Nussbaumer |
|---|---|
| Rok vydání: | 2004 |
| Předmět: |
Stereochemistry
Clinical Biochemistry Pharmaceutical Science CHO Cells Transfection Biochemistry Chemical synthesis chemistry.chemical_compound Inhibitory Concentration 50 Structure-Activity Relationship Cricetinae Drug Discovery Steroid sulfatase Animals Humans Enzyme Inhibitors Imide Molecular Biology IC50 chemistry.chemical_classification Sulfonamides biology Chemistry Organic Chemistry In vitro Sulfonamide Enzyme Enzyme inhibitor biology.protein Molecular Medicine Steryl-Sulfatase |
| Zdroj: | Bioorganicmedicinal chemistry letters. 15(4) |
| ISSN: | 0960-894X |
| Popis: | 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 Ki = 76 nM), they showed only weak inhibition of STS activity in cells (lowest IC50 around 2 μM). 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 IC50 = 270 nM). |
| Databáze: | OpenAIRE |
| Externí odkaz: |
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