QSAR Analysis in 2,4‐Diamino‐6,7‐dimethoxy Quinoline Derivatives – α1‐Adrenoceptor Antagonists – Using the Partial Least Squares (PLS) Method and Theoretical Molecular Descriptors
Marina Cocchi, Maria Cristina Menziani, Giulio Rastelli, Pier Giuseppe De Benedetti · Quantitative Structure-Activity Relationships · 1990
Abstract Theoretical molecular descriptors were derived for fifteen 2,4‐diamino‐6,7‐dimethoxy quinoline derivatives α1‐adrenoceptor antagonists both from molecular orbital indices (AM1) and modelling of molecular shape (QUANTA 2.1.A). Quantitative structure‐activity relationships (QSAR) were obtained between the theoretical descriptors and the α1‐binding affinities (from literature) by using the Partial Least squares (PLS) method. The QSAR model obtained is satisfying both from a predictive and interpretative point of view and clearly depicts the role of the protonated quinoline nucleus at the α1‐adrenoceptor. In fact, the more electrophilic the N1‐H (+) group, the higher the α1‐binding affinity. Furthermore, it suggests that hydrophobicity is a second key feature for an effective receptor interaction.