Syntheses and biological evaluation of novel 2alpha-substituted 1alpha,25-dihydroxyvitamin D3 analogues

Bioorg Med Chem Lett. 2000 May 15;10(10):1129-32. doi: 10.1016/s0960-894x(00)00189-x.

Abstract

Novel 2alpha-substituted 1alpha,25-dihydroxyvitamin D3 analogues were efficiently synthesized and their biological activities were evaluated. 2alpha-Methyl-1alpha,25-dihydroxyvitamin D3 (2), whose unique biological activities were previously reported, was modified to 2alpha-alkyl (ethyl and propyl) and 2alpha-hydroxyalkyl (hydroxymethyl, hydroxyethyl, and hydroxypropyl) analogues 3-7 by elongation of the alkyl chain and/or introduction of a terminal hydroxyl group. 2alpha-Hydroxypropyl-1alpha,25-dihydroxyvitamin D3 (7) exhibited an exceptionally potent calcium-regulating effect and a unique activity profile.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biochemistry / methods
  • Calcitriol / chemistry*
  • Calcitriol / metabolism
  • Calcitriol / pharmacology
  • Calcium Channel Agonists / chemistry
  • Calcium Channel Agonists / metabolism
  • Calcium Channel Agonists / pharmacology
  • Cell Differentiation / drug effects
  • Cholecalciferol / analogs & derivatives*
  • Cholecalciferol / chemistry
  • Cholecalciferol / metabolism
  • Cholecalciferol / pharmacology
  • Drug Evaluation, Preclinical
  • HL-60 Cells / drug effects
  • Humans
  • Receptors, Calcitriol / metabolism
  • Stereoisomerism
  • Structure-Activity Relationship
  • Vitamin D / analogs & derivatives
  • Vitamin D / chemistry
  • Vitamin D-Binding Protein / metabolism

Substances

  • 2-hydroxypropyl-1,25-dihydroxyvitamin D3
  • 2-methyl-1,25-dihydroxyvitamin D3
  • Calcium Channel Agonists
  • Receptors, Calcitriol
  • Vitamin D-Binding Protein
  • Vitamin D
  • Cholecalciferol
  • Calcitriol