Structure-activity relationship studies on vitamin D lactam derivatives as vitamin D receptor antagonist

Bioorg Med Chem Lett. 2008 Aug 1;18(15):4287-90. doi: 10.1016/j.bmcl.2008.06.095. Epub 2008 Jul 3.

Abstract

Structure-activity relationship studies on 1alpha,25-dihydroxyvitamin D(3)-26,23-lactams (DLAMs), antagonists of vitamin D, were conducted, focusing on the substituents of the phenyl group. One of the derivatives (23S,25S)-DLAM-1P-3,5(OEt)(2), showed potent antagonistic activity with an IC(50) of 90nM.

MeSH terms

  • Calcitriol / analogs & derivatives*
  • Calcitriol / chemical synthesis
  • Calcitriol / pharmacokinetics
  • Calcitriol / pharmacology
  • Combinatorial Chemistry Techniques
  • Drug Design
  • Humans
  • Inhibitory Concentration 50
  • Lactams / chemical synthesis
  • Lactams / pharmacokinetics
  • Lactams / pharmacology*
  • Molecular Structure
  • Receptors, Calcitriol / antagonists & inhibitors*
  • Stereoisomerism
  • Structure-Activity Relationship
  • Vitamin D / analogs & derivatives*
  • Vitamin D / chemical synthesis
  • Vitamin D / pharmacokinetics
  • Vitamin D / pharmacology

Substances

  • DLAM-1P compound
  • Lactams
  • Receptors, Calcitriol
  • Vitamin D
  • Calcitriol