Molecular lipophilicity descriptors: a multivariate analysis

Abstract

The importance of lipophilicity in QSAR and drug design demands for the availability of quick, precise and reproducible experimental approaches to quantify this physico-chemical property. The Hansch group introduced the determination of log P in the octanol-water system as the standard. The need to derive lipophilicity data for steadily increasing numbers of compounds initiated the search for both experimental and computational alternatives to octanol-water partitioning. Calculation approaches are either atom-based or use fragments; in recent time attention is paid to the impact of 3D-aspects on lipophilicity. Application of calculation approaches demands a validity check with experimental data. In this study 2 experimental (log P_oct, R_MW) and 17 calculation approaches (fragmental, atom-based, based on molecular properties) are investigated by regression and principal component analysis (PCA) for 159 molecules including simple structures and more complex drugs.