Binding affinities at I1 and I2 Imidazoline Binding Sites (IBS) of a number of properly substituted imidazoline, oxazoline and pyrroline ligands were studied through an integrated modelling approach based on a coordinated application of 2D-(MGZ) and 3D-QSAR (CoMFA- and GRID-GOLPE) analyses and on the development of a quantitative pharmacophore (HypoGen). Congruent and significant cross-validated 2D and 3D correlations, having promising predictive ability, indicated that electrostatic and steric interactions of chiral alpha or beta substituted imidazolines, leading to diverse I1/I2 binding affinities and selectivities, were correctly predicted by the models. Slightly different pharmacophore features were detected by means of Hypogen for I1 and I2 ligands.
Pharmacophore development and 3D-QSAR study of I1 imidazoline binding site ligands
PIGINI, Maria;GENTILI, Francesco;GIANNELLA, Mario;QUAGLIA, Wilma;PIERGENTILI, Alessandro;
2004-01-01
Abstract
Binding affinities at I1 and I2 Imidazoline Binding Sites (IBS) of a number of properly substituted imidazoline, oxazoline and pyrroline ligands were studied through an integrated modelling approach based on a coordinated application of 2D-(MGZ) and 3D-QSAR (CoMFA- and GRID-GOLPE) analyses and on the development of a quantitative pharmacophore (HypoGen). Congruent and significant cross-validated 2D and 3D correlations, having promising predictive ability, indicated that electrostatic and steric interactions of chiral alpha or beta substituted imidazolines, leading to diverse I1/I2 binding affinities and selectivities, were correctly predicted by the models. Slightly different pharmacophore features were detected by means of Hypogen for I1 and I2 ligands.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
