Design, synthesis, and properties of des-D-ring interphenylene derivatives of 1α,25-Dihydroxyvitamin D3

Eur J Med Chem. 2022 Dec 5:243:114795. doi: 10.1016/j.ejmech.2022.114795. Epub 2022 Sep 27.


Novel des-D-ring interphenylene analogs of vitamin D3 were designed on the basis of their conformational analysis and affinity to vitamin D receptor (VDR) estimated using ligand-protein docking simulation. According to this design, a series of the des-D-ring interphenylene analogs were synthesized via Suzuki-Miyaura coupling reactions of des-D, C-ring and A-ring intermediates. A fluorescence polarization VDR competitor assay, a time-resolved fluorescence resonance energy transfer VDR coactivator binding assay, and a human VDR (NR1I1) reporter assay revealed that the des-D-ring interphenylene analogs exhibited a certain VDR binding affinity and ability to promote gene transcription. In particular, analogs having a side chain with an appropriate length at meta position showed high gene transcription promoting activities comparable to those of 1α,25-dihydroxyvitamin D3 and its 19-nor derivative.

Keywords: Des-D-ring; Reporter gene assay; Suzuki-Miyaura coupling; Vitamin D receptor; Vtamin D analog; s.

MeSH terms

  • Cholecalciferol
  • Humans
  • Molecular Conformation
  • Protein Binding
  • Receptors, Calcitriol* / metabolism
  • Vitamin D*


  • 1,25-dihydroxyvitamin D
  • Receptors, Calcitriol
  • Vitamin D
  • Cholecalciferol