Binding affinities at I-1 and I-2 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 differently modulate the binding affinities at I-1/I-2 IBS. Stereoselective interactions of chiral alpha or beta substituted imidazolines, leading to diverse I-1/I-2 binding affinities and selectivities, were correctly predicted by the models. Slightly different pharmacophore features were detected by means of Hypogen for I-1 and I-2-IBS ligands.
Pharmacophore Development and 3D-QSAR Study of I1 Imidazoline Binding Site Ligands / O., Nicolotti; A., Carotti; A., Carrieri; M., Pigini; F., Gentili; Brasili, Livio; M., Giannella; W., Quaglia; A., Piergentili; P., Bousquet; M., Dontenwill. - In: MEDICINAL CHEMISTRY RESEARCH. - ISSN 1054-2523. - STAMPA. - 13:(2004), pp. 170-189.
Pharmacophore Development and 3D-QSAR Study of I1 Imidazoline Binding Site Ligands
BRASILI, Livio;
2004
Abstract
Binding affinities at I-1 and I-2 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 differently modulate the binding affinities at I-1/I-2 IBS. Stereoselective interactions of chiral alpha or beta substituted imidazolines, leading to diverse I-1/I-2 binding affinities and selectivities, were correctly predicted by the models. Slightly different pharmacophore features were detected by means of Hypogen for I-1 and I-2-IBS ligands.Pubblicazioni consigliate
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