Selective analogs of 1α,25-dihydroxyvitamin D3 for the study of specific functions of Vitamin D

New analogs of 1 alpha,25-dihydroxyvitamin D-3 synthesized in our research group that show selective activity in vivo are presented along with supporting biological results. Compounds that act preferentially on intestine are 2-(3'-propylidene-19-nor-(20S or 20R))-1 alpha,25-dihydroxyvitamin D-3 and 2-methylene-19-21-dinor-1 alpha,25-dihydroxyvitamin D-3. Compounds that act anabolically to induce bone formation are 2-methylene-19-nor-(20S)-1 alpha,25-dihydroxyvitamin D-3 (2MD), the 2 alpha-methyl derivative, the 26,27-dimethyl derivative, and the 26-dimethylene derivative. Compounds that act preferentially on parathyroid glands are 2-methylene-19-nor-1 alpha-hydroxy-homopregnacalciferol, the 20S-bishomo derivative and the 2-methylene-19,26,27-trinor-1 alpha,25-dihydroxyvitamin D-3. These latter compounds do not elevate serum calcium until doses of the order of >300 mu g/kg body weight are used, while parathyroid hormone levels are suppressed at much lower doses. Some of these novel analogs may ultimately be useful as new and safer therapeutic agents. Regardless of their clinical utility, they represent valuable research tools that can be used to study the specific functions of the Vitamin D hormone in vivo. (c) 2006 Elsevier Ltd. All rights reserved.