Synthesis of 2beta-substituted-14-epi-previtamin D3 and testing of its genomic activity.
2beta-substituted analogs of 14-epi-previtamin D(3) were synthesized for the first time by the thermal isomerization of the corresponding 14-epi-vitamin D3 that were available using coupling reaction between the A-ring phosphine oxide derived from a chiral epoxide and CD-ring cis-hydrindanone. The VDR binding affinity and transactivation activity of osteocalcin promoter in HOS cells were evaluated, and the new analogs were found to be less active, 0.01-0.18% of VDR binding affinity compared with the natural hormone and EC50 1.0-9.1 nM for transactivation activity, than 14-epi-previtamin D3 with 0.5% (VDR) and EC50 0.46 nM, respectively.
Sawada
Daisuke
D
Faculty of Pharmaceutical Sciences, Teikyo University, 1091-1, Suwarashi, Sagamiko, Sagamihara, Kanagawa 229-0195, Japan.
Tsukuda
Yuya
Y
Saito
Hiroshi
H
Takagi
Ken-ichiro
K
Ochiai
Eiji
E
Ishizuka
Seiichi
S
Takenouchi
Kazuya
K
Kittaka
Atsushi
A
D045744:Cell Line, Tumor; D002626:Chemistry, Pharmaceutical / Q000379:methods; D002762:Cholecalciferol / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D015195:Drug Design; D004852:Epoxy Compounds / Q000737:chemistry; D006801:Humans; D008954:Models, Biological; D008956:Models, Chemical; D015675:Osteocalcin / Q000235:genetics; D010720:Phosphines / Q000737:chemistry; D011401:Promoter Regions, Genetic; D018167:Receptors, Calcitriol / Q000378:metabolism; D013237:Stereoisomerism; D015533:Transcriptional Activation
D004852:Epoxy Compounds; D010720:Phosphines; D018167:Receptors, Calcitriol; D015675:Osteocalcin; D002762:Cholecalciferol; C025168:previtamin D(3)