Estrogenic potential of 2-alkyl-4-(thio)chromenone 6-O-sulfamates: potent inhibitors of human steroid sulfatase.
2-Alkylchromen-4-one 6-O-sulfamates, a new class of potent steroid sulfatase (STS) inhibitors, were evaluated for their estrogenic potential. Structure-activity relationships for estrogenic activity were identified; however, no correlation with STS inhibition was found. Estrogenicity is favored by bulky side chains and can be effectively abrogated by an (additional) linear substituent. Compound 2g, which lacks estrogenicity while potently inhibiting STS, has an ideal in vitro profile for the treatment of breast cancer.
Novartis Research Institute Vienna, Brunnerstrasse 59, A-1235 Vienna, Austria. peter.nussbaumer@pharma.novartis.com
Peter
P
Nussbaumer
Anthony P
AP
Winiski
Andreas
A
Billich
D001578:Benzopyrans / Q000737:chemistry / Q000494:pharmacology*; D001667:Binding, Competitive; D001943:Breast Neoplasms; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D005454:Fluorescence Polarization; D006801:Humans; D008024:Ligands; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism; D043266:Steryl-Sulfatase / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship; D013451:Sulfonic Acids / Q000737:chemistry / Q000494:pharmacology*
D001578:Benzopyrans; D004791:Enzyme Inhibitors; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D008024:Ligands; D011960:Receptors, Estrogen; D013451:Sulfonic Acids; C005741:sulfamic acid; D043266:Steryl-Sulfatase