Difluoromethyl Analogs of the Natural Hormone 1a25-Dihydroxyvitamin D3: Design Synthesis and Preliminary Biological Evaluation

摘要

Three new vitamin D analogs >3-5 incorporating a –CHF2 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-CHF2 analog >3 is higher than that of the 1-CHF2 analog >4.