@article {299, title = {2-Methylene analogs of 1alpha-hydroxy-19-norvitamin D3: synthesis, biological activities and docking to the ligand binding domain of the rat vitamin D receptor}, journal = {The Journal of Steroid Biochemistry and Molecular Biology}, volume = {89-90}, year = {2004}, month = {2004 May}, pages = {13-7}, abstract = {In continuing efforts towards the synthesis of biologically active vitamin D compounds of potential therapeutic value, new 2-methylene-1alpha-hydroxy-19-norvitamin D(3) analogs 3 and 4 with modified alkyl side chains have been synthesized. The key synthetic step involved Lythgoe-type Wittig-Horner coupling of Windaus-Grundmann type ketones 9, possessing different 17beta-alkyl substituents, with the phosphine oxide 10 prepared from (-)-quinic acid. The prepared vitamins 3 and 4 were ca. eight times less potent than 1alpha,25-dihydroxyvitamin D(3) (1alpha,25-(OH)(2)D(3)) (1) in binding to the rat intestinal vitamin D receptor (VDR). In comparison with the hormone 1 they exhibited slightly lower cellular HL-60 differentiation activity. When tested in vivo; the analog 3 was characterized by very high bone calcium mobilizing potency and intestinal calcium transport activity. Unexpectedly, the 25-methyl compound 4 showed marked calcemic activity in both assays. Computational docking of the vitamin 3 into the binding pocket of the rat vitamin D receptor is also reported.}, keywords = {Animals, Binding Sites, Calcitriol, Female, HL-60 Cells, Humans, Hydrocarbons, Ligands, Methane, Mice, Models, Molecular, Rats, Receptors, Calcitriol}, issn = {0960-0760}, doi = {10.1016/j.jsbmb.2004.03.103}, author = {Pawel Grzywacz and Lori A. Plum and Wanda Sicinska and Rafal R. Sicinski and Jean M. Prahl and Hector F. DeLuca} }