Dramatic enhancement of antagonistic activity on vitamin D receptor: a double functionalization of 1alpha-hydroxyvitamin D3 26,23-lactones.
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]
Saito
Nozomi
N
Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa 199-0195, Japan.
Saito
Hiroshi
H
Anzai
Miyuki
M
Yoshida
Akihiro
A
Fujishima
Toshie
T
Takenouchi
Kazuya
K
Miura
Daishiro
D
Ishizuka
Seiichi
S
Takayama
Hiroaki
H
Kittaka
Atsushi
A
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
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