Molecular Similarity Determination of Heteroaromatics Using CoMFA and Multivariate Data Analysis
Thierry Langer · Quantitative Structure-Activity Relationships · 1994
Abstract The molecular similarity concept serves as a tool for rationalizing the design of potential bioactive molecules. This report examines a way to determine molecular similarity among heteroaromatic moieties by calculating new QSAR descriptors using the CoMFA approach. The descriptors for heteroaromatic substituents in organic molecules derived in this study permit to take into account differences in anchoring positions of such substructures in a given molecule. The aromatic moieties 1‐37 have been characterized by their interaction energies calculated using the CoMFA method. Principal component analysis of the interaction energy matrices was performed in order to derive new ‘principal properties’ of the heteroaromatics. A partitioning of the heteroaromatic substituents into families has been done both by hierarchical clustering of the obtained principal components and by applying a factorial design method. These procedures allow a classification of structures according to their molecular similarity.