TOPS-MODE approach for the prediction of blood-brain barrier permeation.

The blood-brain barrier permeation has been investigated by using a topological substructural molecular design approach (TOPS-MODE). A linear regression model was developed to predict the in vivo blood-brain partitioning coefficient on a data set of 119 compounds, treated as the logarithm of the blood-brain concentration ratio. The final model explained the 70% of the variance and it was validated through the use of an external validation set (33 compounds of the 119, MAE = 0.33), a leave-one-out crossvalidation (q(2) = 0.65, S(press) = 0.43), fivefold full crossvalidation (removing 28 compounds in each cycle, MAE = 33, RMSE = 0.43) and the prediction of +/- values for an external test set …