New Principal Components Derived Parameters Describing Molecular Diversity of Heteroaromatic Residues
Thierry Langer, Rémy D. Hoffmann · Quantitative Structure-Activity Relationships · 1998
This study reports on determination of new descriptors for heteroaromatic ring fragments permitting to take into account differences in anchoring positions of such substructures in a given molecule. For a set of 72 aromatic moieties (five- and six-membered monocyclic and benzo fused heteroaromatics containing one or two heteroatoms) parameters including 121 2D physico-chemical descriptors, six receptor surface models descriptors, and three 3D variables have been calculated and new sets of QSAR parameters were generated from principal component analyses of the data matrix this obtained. Hierarchical clustering of the obtained principal components as well as applying both D-optimal design and a new function for molecular estimation allowed partitioning of the heteroaromatic substituents into similar families and permitted a classification of the structures according to their molecular similarity. The descriptors obtained finally were tested for their prediction capacity using a previously reported dataset of biologically active compounds. The results obtained hereby clearly demonstrate the usefulness of the new principal properties.