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