title: Dramatic enhancement of antagonistic activity on vitamin D receptor: a double functionalization of 1alpha-hydroxyvitamin D3 26,23-lactones.
abstract: The synthesis of novel vitamin D receptor antagonists, 24-methyl-1alpha-hydroxyvitamin D(3) 26,23-lactones, is reported. We found that the biological activities of the vitamin D(3) lactones were affected by the structure of the lactone part. Furthermore, introduction of a 2alpha-methyl group into the 24-methylvitamin D(3) lactones dramatically enhanced their anti-vitamin D activity. [reaction: see text]
authors.affiliation: Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa 199-0195, Japan.
authors.forename: Nozomi
authors.initials: N
authors.lastname: Saito
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Saito
authors.forename: Miyuki
authors.initials: M
authors.lastname: Anzai
authors.forename: Akihiro
authors.initials: A
authors.lastname: Yoshida
authors.forename: Toshie
authors.initials: T
authors.lastname: Fujishima
authors.forename: Kazuya
authors.initials: K
authors.lastname: Takenouchi
authors.forename: Daishiro
authors.initials: D
authors.lastname: Miura
authors.forename: Seiichi
authors.initials: S
authors.lastname: Ishizuka
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Takayama
authors.forename: Atsushi
authors.initials: A
authors.lastname: Kittaka
mesh_terms: D002117:Calcitriol / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism; D018922:HL-60 Cells; D006801:Humans; D007783:Lactones / Q000737:chemistry; D015394:Molecular Structure; D012516:Osteosarcoma / Q000201:enzymology; D018167:Receptors, Calcitriol / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013250:Steroid Hydroxylases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D065668:Vitamin D3 24-Hydroxylase
chemical_list: D065607:Cytochrome P-450 Enzyme Inhibitors; D007783:Lactones; D018167:Receptors, Calcitriol; C400545:TEI 9647; D003577:Cytochrome P-450 Enzyme System; D013250:Steroid Hydroxylases; D065668:Vitamin D3 24-Hydroxylase; D002117:Calcitriol