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

Abstract 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 .