Theoretical calculation and prediction of drug transport processes using simple parameters and partial least squares projections to latent structures(PLS) statistics. The use of electrotopological state indices

A method of modeling and predicting drug transport processes using simple, theoretically computed molecular descriptors and multivariate statistics ha s been investigated in four data sets related to Caco-2 cell permeability, human intestinal absorption, brain-blood partitioning, and immobilized arti ficial membrane (IAM) chromatography. The program Molconn-Z was used to com pute theoretical molecular descriptors related to electrotopological state indices. Additional parameters related to size and lipophilicity [i.e., cal culated molar refraction (CMR) and octanol-water partition coefficient (CLO GP)] were also used in the statistical modeling. Good statistical models we re derived (r(2) and Q(2) values ranged from 0.75 to 0.93 and 0.70 to 0.89, respectively) that permit fast computational (electronic) screening and pr ioritization of virtual libraries. (C) 2001 Wiley-Liss, Inc. and the Americ an Pharmaceutical Association.