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

• Published in: Bioorganic & medicinal chemistry letters Vol. 13; no. 21; pp. 3673 - 3677
• Main Authors: NUSSBAUMER, Peter, GEYL, Dieter, HORVATH, Amarylla, LEHR, Philipp, WOLFF, Barbara, BILLICH, Andreas
• Format: Journal Article
• Language: English
• Published: Oxford Elsevier 03.11.2003
• Subjects: Animals; Antineoplastic agents; Biological and medical sciences; CHO Cells; Cricetinae; Drug Design; Drug Evaluation, Preclinical; Enzyme Inhibitors - chemical synthesis; Enzyme Inhibitors - pharmacology; General aspects; Humans; Indicators and Reagents; Kinetics; Medical sciences; Pharmacology. Drug treatments; Steryl-Sulfatase - antagonists & inhibitors; Structure-Activity Relationship; Sulfonylurea Compounds - chemical synthesis; Sulfonylurea Compounds - pharmacology; Enzyme; Nitrogen heterocycle; Combinatorial chemistry; Enzyme inhibitor; Esterases; In vitro; Screening; Structure activity relation; Steryl-sulfatase; Sulfonylureas; Bicyclic compound; Hydrolases; Sulfuric ester hydrolases; Chemical synthesis; Halogen Organic compounds
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2003.08.019

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.