Difluoromethyl analogs of the natural hormone 1alpha,25-dihydroxyvitamin D3: Design, synthesis, and preliminary biological evaluation

Three new Vitamin D analogs 3-5 incorporating a -CHF(2) group as an -OH surrogate have been prepared. Two of these new analogs (3 and 5) are strongly antiproliferative toward murine keratinocytes and are approximately 50 times less calciuric in vivo than the natural hormone calcitriol. The transcriptional activity of the 25-CHF(2) analog 3 is higher than that of the 1-CHF(2) analog 4.