A 3-DIMENSIONAL TECHNIQUE FOR THE CALCULATION OF OCTANOL WATER PARTITION-COEFFICIENTS

Octanol-water partition coefficients, as logPs, are frequently used to describe transportability and membrane permeability of chemical compounds. Because of this they represent an integral part of quantitative structure-activity relationship (QSAR) theory. Since the analytical determination of logPs is a tedious process, many empirical techniques for their calculation have been developed. The additive fragment-based technique, clogP, represents the most highly validated algorithm designed for this purpose. However, it has been observed that clogP is incapable of distinguishing between structural isomers in a congeneric series of compounds. This is primarily a result of the lack of necessary ''factors'' for the characterization of the substituent effects. As an alternative to additional parameterization of the clogP methodology, a novel technique for the calculation of octanol-water partition coefficients based on three-dimensional descriptors was developed which is capable of accurately predicting the experimentally-determined logPs for a congeneric series of structural isomers.