Author： Nikolic K. Filipic S. Agbaba D.
Publisher： Taylor & Francis Ltd
ISSN： 1062-936X
Source： SAR and QSAR in Environmental Research, Vol.20, Iss.1-2, 2009-01, pp. : 133-144
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Abstract
Selective imidazoline1-receptor (I1-R) ligands are used clinically to reduce blood pressure. Thus, there is significant interest in developing new imidazoline analogs with high selectivity and affinity for I1 receptors. A quantitative structure-activity relationship (QSAR) study was carried out on 11 potent I1-R ligands (derivatives of imidazoline, oxazoline and pyrroline) using a multiple linear regression (MLR) procedure. The selected compounds have been studied using B3LYP/3-21G(d, p) and B3LYP/6-31G(d, p) methods. Among the 42 descriptors that were considered in generating the QSAR model, three descriptors (partial atomic charges of nitrogen in the heterocyclic moiety (N-2 charge), log D and the dipole moment of the ligands) resulted in a statistically significant model with r2 > 0.874 and [image omitted] > 0.802. The QSAR models were validated through cross-validation and external test set prediction. The aim of the developed MLR models for the I1-R ligands was to link the structures to their reported I1-R binding affinity log(1/Ki). The proposed QSAR models indicate that an increase in log D and the dipole moment value and a decrease in N-2 charge in the heterocyclic moiety are predictors of better selectivity and affinity for I1 receptors. The developed QSAR model is intended to predict the I1-R binding affinity of related compounds and aid in the rational design of new potent and selective I1-R ligands.
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