Prediction of drug transport processes using simple parameters and PLS statistics - The use of ACD/logP and ACD/ChemSketch descriptors

A method of modelling and predicting biopharmaceutical properties using sim ple theoretically computed molecular descriptors and multivariate statistic s has been investigated for several data sets related to solubility, IAM ch romatography, permeability across Caco-2 cell monolayers, human intestinal perfusion, brain-blood partitioning, and P-glycoprotein ATPase activity. Th e molecular descriptors (e.g. molar refractivity, molar volume, index of re fraction, surface tension and density) and logP were computed with ACD/Chem Sketch and ACD/logP, respectively. Good statistical models were derived tha t permit simple computational prediction of biopharmaceutical properties. A ll final models derived had R-2 values ranging from 0.73 to 0.95 and Q(2) v alues ranging from 0.69 to 0.86. The RMSEP values for the external test set s ranged from 0.24 to 0.85 (log scale). (C) 2001 Elsevier Science B.V. All rights reserved.