Synthesis of novel sigma-receptor ligands from methyl alpha-D-mannopyranoside

Carbohydr Res. 2006 Oct 16;341(14):2321-34. doi: 10.1016/j.carres.2006.06.016. Epub 2006 Jul 18.

Abstract

For the first time a monosaccharide (methyl alpha-D-mannopyranoside) has been used as starting material for the synthesis of novel sigma-receptor ligands. The hept-3-ulopyranoside dimethyl ketals 14 and 15 were obtained from the nitrile 7 via two synthetic routes. After selective hydrolysis of the ketone dimethyl acetal, various amino substituents were introduced into position 3. High sigma(1)-receptor affinity and selectivity was attained with equatorially arranged amino substituents in position 3 and a dichlorophenylacetamide moiety in position 7. The anomeric mixture of dimethylamines 26alpha/beta displayed the highest sigma(1)-receptor affinity (K(i)=21nM) within this small series of test compounds.

MeSH terms

  • Hydrolysis
  • Ligands
  • Mannose / chemistry*
  • Methylmannosides
  • Molecular Structure
  • Radioligand Assay
  • Receptors, sigma / chemistry*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Ligands
  • Methylmannosides
  • Receptors, sigma
  • methylmannoside
  • Mannose