title: A multidetachable sulfamate linker successfully used in a solid-phase strategy to generate libraries of sulfamate and phenol derivatives.
abstract: The sulfamates and phenols constitute two families of compounds with numerous interesting biological properties. Using the ability of a new multidetachable sulfamate linker to generate these two families of compounds from the same resin, we designed and synthesized libraries of estradiol derivatives, sulfamoylated or not. A C-16beta side chain was then judiciously diversified to target two key steroidogenic enzymes, the steroid sulfates and the type 1 17beta-HSD. Four libraries of sulfamate and phenol derivatives were easily obtained by solid-phase parallel synthesis in good crude overall yields (13-62%) and HPLC purities (85-96%). Such strategy using the new two-in-line sulfamate linker could be also extended to other therapeutic targets than steroidogenic enzymes, thus adding to its potential.
authors.affiliation: Medicinal Chemistry Division, Oncology and Molecular Endocrinology Research Center and Laval University, Centre Hospitalier Universitaire de Québec (CHUQ), Pavillon CHUL, 2705 Laurier Boulevard, Québec, Qc, Canada. donald.poirier@crchul.ulaval.ca
authors.forename: Donald
authors.initials: D
authors.lastname: Poirier
authors.forename: Liviu C
authors.initials: LC
authors.lastname: Ciobanu
authors.forename: Marie
authors.initials: M
authors.lastname: Bérubé
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors; D000726:Androgen Antagonists / Q000138:chemical synthesis / Q000494:pharmacology; D002460:Cell Line; D004965:Estrogen Antagonists / Q000138:chemical synthesis / Q000494:pharmacology; D006801:Humans; D007202:Indicators and Reagents; D007700:Kinetics; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D010636:Phenols / Q000138:chemical synthesis*; D013055:Spectrophotometry, Infrared; D013429:Sulfatases / Q000037:antagonists & inhibitors / Q000096:biosynthesis; D013451:Sulfonic Acids / Q000138:chemical synthesis*
chemical_list: D000726:Androgen Antagonists; D004965:Estrogen Antagonists; D007202:Indicators and Reagents; D010636:Phenols; D013451:Sulfonic Acids; C005741:sulfamic acid; D015067:17-Hydroxysteroid Dehydrogenases; D013429:Sulfatases