Strategies to improve in vivo toxicology outcomes for basic candidate drug molecules.

A valid PLS-DA model to predict attrition in pre-clinical toxicology for basic oral candidate drugs was built. A combination of aromatic/aliphatic balance, flatness, charge distribution and size descriptors helped predict the successful progression of compounds through a wide range of toxicity testing. Eighty percent of an independent test set of marketed post-2000 basic drugs could be successfully classified using the model, indicating useful forward predictivity. The themes within this work provide additional guidance for medicinal design chemists and complement other literature property guidelines.