Structural development of non-secosteroidal vitamin D receptor (VDR) ligands without any asymmetric carbon

Bioorg Med Chem. 2018 Dec 15;26(23-24):6146-6152. doi: 10.1016/j.bmc.2018.11.008. Epub 2018 Nov 9.

Abstract

Non-secosteroidal VDR ligands without any assymmetric carbon were designed and synthesized based on the structure of the previously reported non-secosteroidal VDR agonist LG190178. The VDR-agonistic activity of all synthesized compounds was evaluated, and 7b emerged as a potent agonist activity with an EC50 value of 9.26 nM. Moreover, a docking simulation analysis was also performed to determine the binding mode of 7b with VDR-LBD.

Keywords: Asymmetric carbon; Docking study; Non-secosteroid; Vitamin D receptor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biphenyl Compounds / chemical synthesis
  • Biphenyl Compounds / chemistry
  • Biphenyl Compounds / pharmacology*
  • Dose-Response Relationship, Drug
  • Humans
  • Ligands
  • Models, Molecular
  • Molecular Structure
  • Receptors, Calcitriol / agonists*
  • Structure-Activity Relationship

Substances

  • Biphenyl Compounds
  • Ligands
  • Receptors, Calcitriol
  • VDR protein, human
  • YR301