T. Langer et Rd. Hoffmann, NEW PRINCIPAL COMPONENTS DERIVED PARAMETERS DESCRIBING MOLECULAR DIVERSITY OF HETEROAROMATIC RESIDUES, Quantitative structure-activity relationships, 17(3), 1998, pp. 211-223
This study reports on determination of new descriptors for heteroaroma
tic ring fragments permitting to take into account differences in anch
oring positions of such substructures in a given molecule. For a set o
f 72 aromatic moieties (five- and six-membered monocyclic and benzo fu
sed heteroaromatics containing one or two heteroatoms) parameters incl
uding 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 o
f the data matrix this obtained. Hierarchical clustering of the obtain
ed principal components as well as applying both D-optimal design and
a new function for molecular estimation allowed partitioning of the he
teroaromatic substituents into similar families and permitted a classi
fication of the structures according to their molecular similarity. Th
e descriptors obtained finally were tested for their prediction capaci
ty using a previously reported dataset of biologically active compound
s. The results obtained hereby clearly demonstrate the usefulness of t
he new principal properties.