Abstract
Three side-chain fluorinated analogues of vitamin D3 were tested for their bone-resorbing activity on fetal rat forelimb bones in vitro. Two fluoro derivatives of 25-hydroxyvitamin D3 (25-OH-D3), 24,24-difluoro-25-hydroxyvitamin D3 and 25-hydroxy-26,26,26,27,27,27-hexafluorovitamin D3, were compared with 25-OH-D3. The difluoro compound was approximately 7 times more potent than 25-OH-D3, and the hexafluoro analogue was approximately 40 times more potent than 25-OH-D3 in this system. In contrast, the 24,24-difluoro analogue of lα,25-dihydroxyvitamin D3 (lα,25-(OH)2D3) was slightly less potent than lα,25-(OH)2D3. The results indicate that the presence of fluoride groups on carbon atoms immediately adjacent to the 25-hydroxyl group enhances the in vitro bone-resorbing effects of 25-hydroxyvitamin D3. On the other hand, fluorination of the lα-hydroxylated compound on position 24 actually diminished rather than increased bone-resorptive activity.
ACKNOWLEDGMENT We thank Thalia Mavreas for her excellent technical assistance.
- Copyright © 1981 by The American Society for Pharmacology and Experimental Therapeutics
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