N-Arylalkyl-2-azaadamantanes as cage-expanded polycarbocyclic sigma (σ) receptor ligands

Bioorg Med Chem Lett. 2011 Sep 15;21(18):5289-92. doi: 10.1016/j.bmcl.2011.07.028. Epub 2011 Jul 14.

Abstract

A series of racemic N-arylalkyl-2-azaadamantan-1-ols (9-15) and the corresponding deoxygenated, achiral N-arylalkyl-2-azaadamantanes (23-29) were synthesized and screened in competition binding assays against a panel of CNS targets. Adamantyl hemiaminals 9-15 displayed generally low affinity for both σ(1) (K(i) values= 294-1950 nM) and σ(2) receptors (K(i) values=201-1020 nM), and negligible affinity for 42 other CNS proteins. Deoxygenation of 9-15 to give the corresponding achiral azaadamantanes 23-29 greatly improved affinity for σ(1) (K(i) values=8.3-239 nM) and σ(2) receptors (K(i) values=34-312 nM).

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adamantane / analogs & derivatives
  • Adamantane / chemistry
  • Adamantane / pharmacology*
  • Ligands
  • Molecular Structure
  • Receptors, sigma / antagonists & inhibitors*
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • Ligands
  • Receptors, sigma
  • Adamantane