Development of analogues of 1alpha,25-dihydroxyvitamin D3 with biased side chain orientation: methylated des-C,D-homo analogues.
The discovery that 1alpha,25-dihydroxyvitamin D3 is effective in the inhibition of cellular proliferation and in the induction of cellular differentiation has led to a search for analogues in which these activities and the classical calcemic activity of this hormone are separated. In this context, the synthesis and biological evaluation are reported of the three stereoisomeric CD-ring modified structural analogues in order to enforce a particular and different orientation of the 25-hydroxylated side chain. Comparison of the results of the biological evaluation and conformational analysis of the side chain suggests one defined and "active" geometry.
Gabriëls
S
S
Department of Organic Chemistry, Ghent University, Belgium.
Van Haver
D
D
Vandewalle
M
M
De Clercq
P
P
Verstuyf
A
A
Bouillon
R
R
D002117:Calcitriol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D006801:Humans; D008958:Models, Molecular; D015394:Molecular Structure; D013057:Spectrum Analysis; D014407:Tumor Cells, Cultured
D002117:Calcitriol