Ring-A-seco analogs of 1α,25-dihydroxy-19-norvitamin D3

J Steroid Biochem Mol Biol. 2013 Jul:136:39-43. doi: 10.1016/j.jsbmb.2012.09.030. Epub 2012 Oct 9.


The steroid hormone 1α,25-dihydroxyvitamin D3 [1α,25-(OH)2D3] is the most active metabolite of vitamin D3 which exerts its control over a multitude of biological processes related to calcium and phosphorus homeostasis, cell proliferation and differentiation, and immune regulation. Unfortunately, the therapeutic application of 1α,25-(OH)2D3 is limited by induction of hypercalcemia. The need for vitamin D compounds with selective biological profiles has stimulated the synthesis of more than three thousand analogs of 1α,25-(OH)2D3. Most of these compounds have structural modifications in the side chain and A-ring; there is also an increasing number of modifications in the CD-rings and limited number in the triene system (seco-B ring). Herein, we report the synthesis and biological evaluation of seco-A-19-nor analogs of 1α,25-dihydroxyvitamin D3, developed to study the role of ring A in the biological activity of 1α,25-(OH)2D3. Interestingly, compounds 2 and 4 show substantial ability to bind the vitamin D receptor and the former is also characterized by selective intestinal calcium transport activity. This article is part of a Special Issue entitled 'Vitamin D Workshop'.

Publication types

  • Review

MeSH terms

  • Animals
  • Binding Sites
  • Calcitriol / analogs & derivatives*
  • Calcitriol / chemical synthesis
  • Calcitriol / pharmacology
  • Calcium / metabolism
  • Cell Differentiation / drug effects
  • Chemistry Techniques, Synthetic
  • Drug Evaluation, Preclinical
  • HL-60 Cells
  • Humans
  • Models, Molecular
  • Rats
  • Receptors, Calcitriol / chemistry
  • Receptors, Calcitriol / metabolism
  • Structure-Activity Relationship
  • Transcription, Genetic / drug effects


  • Receptors, Calcitriol
  • Calcitriol
  • Calcium