Development of analogues of 1 alpha,25-dihydroxyvitamin D-3 with biased side chain orientation: Methylated des-C,D-homo analogues

The discovery that 1 alpha ,25-dihydroxyvitamin D-3 is effective in the inh ibition of cellular proliferation and in the induction of cellular differen tiation 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 stereoi someric CD-ring modified structural analogues in order to enforce a particu lar 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.