24,24 - difluorierte analogue of 1 alpha, 25 dihydroxy vitamin d3

摘要

Fluorinated analogs of lα,25-dihydroxy vitamin D3. These analogs are synthesized in a convergent manner by joining A-ring and C,D-ring fragments. Each hybrid analog, having a calcemia-lowering 1-hydroxymethyl group and a potentiating 16-ene-24,24-difluorinated C,D-ring and side chain, is designed to be lipophilic and inert toward 24-hydroxylase enzyme catabolism. Each hybrid analog with 1β,3α-substituent stereochemistry shows a pharmacologically desirable combination of high antiproliferative and high transcriptional activities in vitro and also low calcemic activity in vivo.