A simple model to predict blood-brain barrier permeation from 3D molecular fields

We report a four-component partial least squares discriminant analysis (PLS) model for the prediction of blood-brain barrier (BBB) permeation using descriptors derived from 3D molecular fields. The 3D fields were transformed by VolSurf into suitable 1D descriptors, which were correlated to the ratio of blood-brain partitioning measured at steady state in rats (log C-brain/C-blood). The model so obtained sheds light on molecular properties influencing BBB permeation. It can also be used in the virtual screening of new chemicals. (C) 2002 Elsevier Science B.v. All rights reserved.