The difference between 14-epi-previtamin D3 and 14-epi-19-norprevitamin D3: their synthesis and binding affinity for human VDR.
The synthesis of 14-epi-1α,25(OH)(2)previtamin D(3), 14-epi-19-nor-1α,25(OH)(2)previtamin D(3), and their 2-substituted analogs is described. The vitamin D receptor (VDR) binding affinity was further evaluated and 2α-methyl substituted 14-epi-1α,25(OH)(2)previtamin D(3) had 17-fold more potent affinity than 14-epi-1α,25(OH)(2)previtamin D(3).In the comparison of these compounds, the effects of thermal equilibrium, with or without 19-carbon at the A-ring, and their CD-ring structures are discussed.
Faculty of Pharmaceutical Sciences, Teikyo University, Sagamihara, Kanagawa 252-5195, Japan. akittaka@pharm.teikyo-u.ac.jp
Daisuke
D
Sawada
Tomoyuki
T
Katayama
Yuya
Y
Tsukuda
Nozomi
N
Saito
Hiroshi
H
Saito
Shinji
S
Kakuda
Midori
M
Takimoto-Kamimura
Kazuya
K
Takenouchi
Atsushi
A
Kittaka
D002762:Cholecalciferol / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D015394:Molecular Structure; D011485:Protein Binding; D018167:Receptors, Calcitriol / Q000378:metabolism*; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D018167:Receptors, Calcitriol; D002762:Cholecalciferol; C025168:previtamin D(3)