26- and 27-Methyl groups of 2-substituted, 19-nor-1α,25-dihydroxylated vitamin D compounds are essential for calcium mobilization in vivo.
Bioorg Chem
; 47: 9-16, 2013 Apr.
Article
em En
| MEDLINE
| ID: mdl-23474215
ABSTRACT
Twelve new analogs of 19-nor-1α,25-dihydroxyvitamin D36-17, were prepared by a multi-step procedure from known alcohols 18 and 19. We have examined the influence of removing two methyl groups located at C-25, as well as the 25-hydroxy group, on the biological in vitro and in vivo biological activity. Surprisingly, removal of the 26- and 27-methyl groups from either the 2α-methyl or 2-methylene-19-nor-1α,25-dihydroxyvitamin D3 reduced vitamin D receptor binding, HL-60 differentiation, and 25-hydroxylase transcription in vitro only slightly to moderately (compounds 6-13). However, these compounds were devoid of in vivo bone mobilization activity and had markedly reduced activity on intestinal calcium transport. The analogs 14-17 with a 2ß-methyl substitution had little or no activity in vitro and in vivo as expected from previous work.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Vitamina D
/
Cálcio
Limite:
Animals
/
Humans
Idioma:
En
Ano de publicação:
2013
Tipo de documento:
Article