Development of Quantitative Structure - Property Relationship Models for Early ADME Evaluation in Drug Discovery. 2. Blood-Brain Barrier Penetration

Document Type

Article

Publication Date

12-1-2001

Description

A new molecular lipoaffinity descriptor was introduced in this paper to account for the effect of molecular hydrophobicity on blood-brain barrier penetration. The descriptor was defined based on Kier and Hall's atom-type electrotopological state indices. Its evaluation requires 2-D molecular bonding information only. A multiple linear regression equation using this descriptor and molecular weight reproduces the experimental logBB values of 55 training set compounds and 11 test set compounds satisfactorily with statistical parameters nearly identical to the best models based on polar surface area and ClogP. The results indicate that the lipoaffinity descriptor defined in this paper may be a significant descriptor for molecular transport properties across lipid bilayers.

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