title: 17β-HSD2 inhibitors for the treatment of osteoporosis: Identification of a promising scaffold.
abstract: 17β-Hydroxysteroid dehydrogenase type 2 (17β-HSD2) catalyses the conversion of active 17β-hydroxysteroids into the less active 17-ketosteroids thereby controlling the availability of biologically active estrogens (E2) and androgens (T) in the tissues. The skeletal disease osteoporosis occurs mainly in post-menopausal women and in elderly men when the levels of estrogens and androgens, respectively, decrease. Since 17β-HSD2 is present in osteoblasts, inhibition of this enzyme may provide a new and promising approach to prevent the onset of osteoporosis, keeping a certain level in estrogens and androgens in bone cells of ageing people. Hydroxynaphthyl, hydroxyphenyl and hydroxymethylphenyl-substituted moieties were synthesised as mimetics of the steroidal substrate. Compound 8 has been identified as promising scaffold for 17β-HSD2 inhibitors displaying high activity and good selectivity toward 17β-HSD1, ERα and ERβ.
authors.affiliation: Saarland University, Saarbrücken, Germany.
authors.forename: Marie
authors.initials: M
authors.lastname: Wetzel
authors.forename: Sandrine
authors.initials: S
authors.lastname: Marchais-Oberwinkler
authors.forename: Rolf W
authors.initials: RW
authors.lastname: Hartmann
mesh_terms: D015067:17-Hydroxysteroid Dehydrogenases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D001713:Biphenyl Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D047628:Estrogen Receptor alpha / Q000037:antagonists & inhibitors / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000037:antagonists & inhibitors / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D009281:Naphthalenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D010024:Osteoporosis / Q000188:drug therapy*; D013329:Structure-Activity Relationship
chemical_list: D001713:Biphenyl Compounds; D004791:Enzyme Inhibitors; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D009281:Naphthalenes; D015067:17-Hydroxysteroid Dehydrogenases