Development of quantitative structure-property relationship models for early ADME evaluation in drug discovery. 2. Blood-brain barrier penetration

A new molecular lipoaffinity descriptor was introduced in this paper to acc ount for the effect of molecular hydrophobicity on blood-brain barrier pene tration. The descriptor was defined based on Kier and Hall's atom-type elec trotopological state indices. Its evaluation requires 2-D molecular bonding information only. A multiple linear regression equation using this descrip tor and molecular weight reproduces the experimental logBB values of 55 tra ining set compounds and 11 test set compounds satisfactorily with statistic al parameters nearly identical to the best models based on polar surface ar ea and ClogP. The results indicate that the lipoaffinity descriptor defined in this paper may be a significant descriptor for molecular transport prop erties across lipid bilayers.