Remarkable effect of 2[small alpha]-modification on the VDR antagonistic activity of 1small alpha-hydroxyvitamin D3-26,23-lactones.
Novel 2[small alpha]-methyl-, 2[small alpha]-(3-hydroxypropyl)- and 2[small alpha]-(3-hydroxypropoxy)-substituted 25-dehydro-1[small alpha]-hydroxyvitamin D-26,23-lactone derivatives were efficiently synthesized Reformatsky type allylation and palladium-catalyzed alkenylative cyclization processes, and their biological activities were evaluated. Introducing functional groups into the 2[small alpha]-position of the vitamin D-26,23-lactones resulted in remarkable enhancement of their antagonistic activity on vitamin D receptor (VDR).
Saito
Nozomi
N
Faculty of Pharmaceutical Sciences, Teikyo University, Kanagawa 199-0195, Japan.
Matsunaga
Toshihiro
T
Fujishima
Toshie
T
Anzai
Miyuki
M
Saito
Hiroshi
H
Takenouchi
Kazuya
K
Miura
Daishiro
D
Ishizuka
Seiichi
S
Takayama
Hiroaki
H
Kittaka
Atsushi
A
D000818:Animals; D001667:Binding, Competitive; D002117:Calcitriol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D018922:HL-60 Cells; D006801:Humans; D020128:Inhibitory Concentration 50; D008956:Models, Chemical; D015394:Molecular Structure; D051381:Rats; D018167:Receptors, Calcitriol / Q000037:antagonists & inhibitors*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D018167:Receptors, Calcitriol; C026947:1,25-dihydroxyvitamin D3-26,23-lactone; D002117:Calcitriol; D002118:Calcium