GRIND-derived pharmacophore model for a series of alpha-tropanyl derivative ligands of the sigma-2 receptor

J Comput Aided Mol Des. 2004 May;18(5):361-74. doi: 10.1023/b:jcam.0000047815.22931.3b.

Abstract

A pharmacophore model for the sigma-2 receptor was derived using GRIND (GRid INdependent Descriptors) descriptors arising from a 3D-level procedure whose main prerogative is that it does not require ligand alignment. PLS models for sigma-2 affinity (sigma-2 model: r2=0.83, q2=0.63) and sigma-1/sigma-2 selectivity (r2=0.72, q2=0.46) were derived using a series of alpha-tropanyl derivatives. The models provide pictures of the virtual receptor site (VRS) significant enough to attain a qualitative pharmacophoric representation of the sigma receptor. They give the internal geometrical relationships within two hydrophobic areas (hydrophobic-1 and -2) and a H-bond donor receptor region with which ligands establish non-covalent bonds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Computer Simulation
  • Ligands
  • Models, Molecular
  • Receptors, sigma / metabolism*
  • Tropanes / chemistry*
  • Tropanes / metabolism

Substances

  • Ligands
  • Receptors, sigma
  • Tropanes
  • sigma-2 receptor