title: GRIND-derived pharmacophore model for a series of alpha-tropanyl derivative ligands of the sigma-2 receptor.
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.
authors.affiliation: Department of Pharmaceutical Sciences, University of Florence, via U Schiff 6, 1-50019 Sesto Fiorentino, Firenze, Italy. paola.gratteri@unifi.it
authors.forename: Paola
authors.initials: P
authors.lastname: Cratteri
authors.forename: M Novella
authors.initials: MN
authors.lastname: Romanelli
authors.forename: Gabriele
authors.initials: G
authors.lastname: Cruciani
authors.forename: Claudia
authors.initials: C
authors.lastname: Bonaccini
authors.forename: Fabrizio
authors.initials: F
authors.lastname: Melani
mesh_terms: D003198:Computer Simulation; D008024:Ligands; D008958:Models, Molecular; D017480:Receptors, sigma / Q000378:metabolism*; D014326:Tropanes / Q000737:chemistry* / Q000378:metabolism
chemical_list: D008024:Ligands; D017480:Receptors, sigma; D014326:Tropanes; C106107:sigma-2 receptor