Synthesis of N-substituted 9-azabicyclo[3.3.1]nonan-3alpha-yl carbamate analogs as sigma2 receptor ligands

Bioorg Med Chem. 2006 Oct 15;14(20):6988-97. doi: 10.1016/j.bmc.2006.06.028. Epub 2006 Jul 11.

Abstract

A series of N-substituted 9-azabicyclo[3.3.1]nonan-3alpha-yl phenylcarbamate analogs was prepared and their affinities for sigma (sigma(1) and sigma(2)) receptors were measured in vitro. The results of their structure-activity relationship study identified two new compounds, N-(9-(4-aminobutyl)-9-azabicyclo[3.3.1]nonan-3alpha-yl)-N'-(2-methoxy-5-methylphenyl)carbamate and N-(9-(6-aminohexyl)-9-azabicyclo[3.3.1]nonan-3alpha-yl)-N'-(2-methoxy-5-methylphenyl)carbamate, having a high affinity and selectivity for sigma(2) versus sigma(1) receptors. These compounds were also used in the preparation of biotinylated and fluorescent probes of the sigma(2) receptor.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Aza Compounds / chemical synthesis*
  • Aza Compounds / chemistry
  • Aza Compounds / pharmacology*
  • Binding Sites
  • Carbamates / chemical synthesis*
  • Carbamates / chemistry
  • Carbamates / pharmacology*
  • Guinea Pigs
  • In Vitro Techniques
  • Ligands
  • Molecular Structure
  • Rats
  • Receptors, sigma / antagonists & inhibitors*
  • Sigma-1 Receptor
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Aza Compounds
  • Carbamates
  • Ligands
  • Receptors, sigma
  • sigma-2 receptor