Theoretical Property Predictions

Abstract

Methods for the prediction of octanol/water partition coefficient, aqueous solubility and acid/base dissociation constants are described and discussed. The advantages and limitations of the different approaches are described and an indication of problem areas discussed. Available prediction software is described and listed and attempts are made to assess the likely reliability of the predictions. The concept of “drug-likeness” is introduced and put into context and models for the prediction of ADME properties and toxicity are briefly described and assessed. Software for ADME/toxicity prediction is listed and the impact of these techniques on current drug design efforts is described. Web references are given for both commercial and public domain software which is available for property prediction from chemical structure.

Keywords: Aqueous solubility, partition coefficient, pKa, distribution coefficient, absorption, distribution, metabolism, excretion, drug likeness