Dramatic enhancement of antagonistic activity on vitamin D receptor: a double functionalization of 1alpha-hydroxyvitamin D3 26,23-lactones

Org Lett. 2003 Dec 11;5(25):4859-62. doi: 10.1021/ol035922w.

Abstract

The synthesis of novel vitamin D receptor antagonists, 24-methyl-1alpha-hydroxyvitamin D(3) 26,23-lactones, is reported. We found that the biological activities of the vitamin D(3) lactones were affected by the structure of the lactone part. Furthermore, introduction of a 2alpha-methyl group into the 24-methylvitamin D(3) lactones dramatically enhanced their anti-vitamin D activity. [reaction: see text]

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcitriol / analogs & derivatives*
  • Calcitriol / chemical synthesis*
  • Calcitriol / pharmacology
  • Cell Differentiation / drug effects
  • Cytochrome P-450 Enzyme Inhibitors
  • Cytochrome P-450 Enzyme System / genetics
  • Cytochrome P-450 Enzyme System / metabolism
  • HL-60 Cells
  • Humans
  • Lactones / chemistry
  • Molecular Structure
  • Osteosarcoma / enzymology
  • Receptors, Calcitriol / antagonists & inhibitors*
  • Receptors, Calcitriol / metabolism
  • Steroid Hydroxylases / antagonists & inhibitors
  • Steroid Hydroxylases / genetics
  • Steroid Hydroxylases / metabolism
  • Vitamin D3 24-Hydroxylase

Substances

  • Cytochrome P-450 Enzyme Inhibitors
  • Lactones
  • Receptors, Calcitriol
  • TEI 9647
  • Cytochrome P-450 Enzyme System
  • Steroid Hydroxylases
  • Vitamin D3 24-Hydroxylase
  • Calcitriol