Synthesis and evaluation of a 3-position diastereomer of 1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)vitamin D3 (ED-71)

Bioorg Med Chem. 2006 Dec 1;14(23):8050-6. doi: 10.1016/j.bmc.2006.07.039.

Abstract

A 3-position diastereomer of 1alpha,25-dihydroxy-2beta-(3-hydroxypropoxy)vitamin D3 (ED-71, 2), 3-epi-ED-71 (4), was synthesized by the convergent method coupling the A-ring fragment (5) with the C/D-ring fragment (6). As the results of preliminary in vitro biological evaluation of 3-epi-ED-71 (4), the inhibition of parathyroid hormone secretion in bovine parathyroid cells and binding affinity to human recombinant vitamin D receptor and to human vitamin D binding protein in comparison with ED-71 (2), 1alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3, 1), and 3-epi-1,25(OH)2D3 (3) are described.

MeSH terms

  • Animals
  • Cattle
  • Cholecalciferol / chemical synthesis*
  • Cholecalciferol / chemistry
  • Cholecalciferol / pharmacology*
  • Parathyroid Glands / cytology
  • Parathyroid Hormone / antagonists & inhibitors
  • Parathyroid Hormone / metabolism
  • Protein Binding
  • Receptors, Calcitriol / metabolism
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Parathyroid Hormone
  • Receptors, Calcitriol
  • Cholecalciferol