کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
1355644 1500467 2013 8 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
26- and 27-Methyl groups of 2-substituted, 19-nor-1α,25-dihydroxylated vitamin D compounds are essential for calcium mobilization in vivo
موضوعات مرتبط
مهندسی و علوم پایه شیمی شیمی آلی
پیش نمایش صفحه اول مقاله
26- and 27-Methyl groups of 2-substituted, 19-nor-1α,25-dihydroxylated vitamin D compounds are essential for calcium mobilization in vivo
چکیده انگلیسی

Twelve new analogs of 19-nor-1α,25-dihydroxyvitamin D36–17, 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 2α-methyl or 2-methylene-19-nor-1α,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 2β-methyl substitution had little or no activity in vitro and in vivo as expected from previous work.

Figure optionsDownload as PowerPoint slideHighlights
► 26- and 27-Methyl groups of 19-nor-1,25(OH)2D required for Ca mobilization in vivo.
► A β-methyl on C-2 of 19-nor-1,25-(OH)2D eliminates in vitro and in vivo activity.
► 26,27-Methyls of 19-nor-1,25(OH)2D3 are not required for intestinal Ca transport.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Bioorganic Chemistry - Volume 47, April 2013, Pages 9–16
نویسندگان
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