26- and 27-Methyl groups of 2-substituted, 19-nor-1¦Á,25-dihydroxylated vitamin D compounds are essential for calcium mobilization in vivo

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• 作者：Pawel Grzywacz ; Lori A. Plum ; Margaret Clagett-Dame ; Hector F. DeLuca ; ^{deluca@biochem.wisc.edu}
• 关键词：Analogs of 19-nor-1¦Á ; 25-dihydroxyvitamin D3 ; 26- and 27-Methyl groups ; Bone mobilization
• 刊名：Bioorganic Chemistry
• 出版年：2013
• 出版时间：April, 2013
• 年：2013
• 卷：47
• 期：Complete
• 页码：9-16
• 全文大小：1343 K

文摘

Twelve new analogs of 19-nor-1¦Á,25-dihydroxyvitamin D₃ 6-17, were prepared by a multi-step procedure from known alcohols 18 and 19. We have examined the influence of removing two methyl groups located at C-25, as well as the 25-hydroxy group, on the biological in vitro and in vivo biological activity. Surprisingly, removal of the 26- and 27-methyl groups from either the 2¦Á-methyl or 2-methylene-19-nor-1¦Á,25-dihydroxyvitamin D₃ reduced vitamin D receptor binding, HL-60 differentiation, and 25-hydroxylase transcription in vitro only slightly to moderately (compounds 6-13). However, these compounds were devoid of in vivo bone mobilization activity and had markedly reduced activity on intestinal calcium transport. The analogs 14-17 with a 2¦Â-methyl substitution had little or no activity in vitro and in vivo as expected from previous work.