CALCIUM-REGULATING ACTIVITY OF MO-24,24-DIFLUORO-1-ALPHA,25-DIHYDROXYVITAMIN-D(3) AND YL-24,24-DIFLUORO-1-ALPHA,25-DIHYDROXYVITAMIN-D(3)

Two fluoro analogs of 1alpha,25-dihydroxyvitamin D3 [1,25(OH)2D3], 24a -homo-24,24-difluoro-1alpha,25-dihydroxyvitamin D3 [24aF2-homo-1,25(OH )2D3], and dimethyl-24,24-difluoro-1alpha,25-dihydroxyvitamin D3 [24F2 -1,25(OH)2(Me)2D3] were examined for calcium (Ca)-regulating activity. The objective of the present study was to determine whether or not fl uoro substitution at 24-position would alter activities of the origina l compounds, that is, 26,27-dimethyl 1alpha, 25-dihydroxyvitamin. D3[1 ,25(OH)2 (Me)2D3] and -1alpha,25-dihydroxyvitaminD3[24homo-1,25(OH)2D3 ], respectively. The relative activities of 24aF2-homo-1,25(OH)2D3 24F 2-1,25(OH)2(Me)2D3, and 1,25(OH)2D3 in competing with 1,25(OH)2D, for binding to chick intestinal cytosol receptor were 0.28:0.5:1.0. The re lative potencies of the same series of compounds in competition for th e vitamin D-deficient rat serum binding sites were 0.04:0.15:1. Bone-r esorbing activities of two fluoro analogs in cultures of neonatal mous e parietal bones were more potent than that of 1,25(OH)2D3. Similar re sults were recognized in stimulating activities of osteoclast-like cel l formation. Responses of two fluoro analogs to intestinal Ca absorpti on were similar to that of 1,25(OH)2D3. The potencies of 1,25(OH)2D3 a nd its fluoro analogs in bone Ca mobilization were the highest with 1, 25(OH)2D3, followed by 24F2-1,25(OH)2(Me)2D3, and 24aF2-homo-1,25(OH)2 D3, in that order. From these results and the data of Paulson et al. [ 24], fluoro substitution in 24-position of 1,25(OH)2D3 apparently does not alter their activities, hence, the fluoro substitution at 24-posi tion of 1,25(OH)2D3 and the elongation of side chain of 1,25(OH)2D3 ma y not intensify Ca-regulating activity.