Scaled polar surface area descriptors:development and application to three sets of partition coefficients

摘要

Modifications to the standard definition of polar surface area (PSA)are reported and tested against the octanol water,chloroform water and cyclohexane-water partition coefficients of 110 organic and drug-like molecules.It is shown that increasing the flexibility of PSA-based models can lead to some improvements in accuracy,but that these still fall well short of previously published methods.To compete with such methods,PSA-based descriptors must be scaled according to the known hydrogen bonding characteristics of common functional groups.Introducing this scaling markedly improves accuracy,with predictive errors typically around one-half of a log P unit,confirmed by splitting the data into training and test sets.All models developed follow known characteristics of the partition coefficients considered and are statistically and chemically valid.