Methyl substitution of the 25-hydroxy group on 2-methylene-19-nor-1α,25-dihydroxyvitamin D3 (2MD) reduces potency but allows bone selectivity

摘要: Abstract The discovery of 2-methylene-19-nor-1α,25-dihydroxyvitamin D 3 (2MD) as a bone selective and anabolic form vitamin has stimulated an investigation structure/function selectivity. Four new 2-substituted-19-norvitamin analogs – 6 have been developed to study the structure–activity relationship at C-25. As predicted, removing 25-hydroxy group (compound ) from very potent analog 2MD its 2-methyl derivatives ( 5 dramatically reduces in vitro activities, but biological potency is nearly fully restored vivo likely due 25-hydroxylation. introduction methyl C-25 4 that blocks 25-hydroxylation activity both . However, retains selectivity making it interesting possible therapeutic for loss diseases.