Remarkable effect of 2[small alpha]-modification on the VDR antagonistic activity of 1small alpha-hydroxyvitamin D3-26,23-lactones

Org Biomol Chem. 2003 Dec 21;1(24):4396-402. doi: 10.1039/b311107e. Epub 2003 Nov 6.

Abstract

Novel 2[small alpha]-methyl-, 2[small alpha]-(3-hydroxypropyl)- and 2[small alpha]-(3-hydroxypropoxy)-substituted 25-dehydro-1[small alpha]-hydroxyvitamin D-26,23-lactone derivatives were efficiently synthesized Reformatsky type allylation and palladium-catalyzed alkenylative cyclization processes, and their biological activities were evaluated. Introducing functional groups into the 2[small alpha]-position of the vitamin D-26,23-lactones resulted in remarkable enhancement of their antagonistic activity on vitamin D receptor (VDR).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding, Competitive
  • Calcitriol / analogs & derivatives*
  • Calcitriol / chemical synthesis
  • Calcitriol / chemistry
  • Calcitriol / pharmacology*
  • Calcium / metabolism
  • Cell Differentiation / drug effects
  • Cell Line, Tumor
  • HL-60 Cells
  • Humans
  • Inhibitory Concentration 50
  • Models, Chemical
  • Molecular Structure
  • Rats
  • Receptors, Calcitriol / antagonists & inhibitors*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Receptors, Calcitriol
  • 1,25-dihydroxyvitamin D3-26,23-lactone
  • Calcitriol
  • Calcium