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     ...Introduction to B-B Partitioning

Definition of Log BB Property Data

Blood/Brain Barrier penetration property data is based on a measure of the partitioning of a compound across the blood-brain barrier.  The property is measured experimentally as the ratio of the concentration in the brain, [brain], to that in the blood, [blood]:

BB = [ brain ]  /  [ blood ]

The logarithm of BB is the value typically reported in the available literature.  The quantitative value of logBB is thought to be related to, molecular size, lipophilicity, local hydrophobicity , and molecular flexibility, (1) but no explicit mathematical relationship between the logBB value and these structural characteristics has yet been given.

(1)  P. Crivori (2000) J. Med Chem 43, 2204

Phisiology of the The Blood Brain Barrier

The BBB is formed by continuous network of tight junctions within the endothelium of capillaries and thereby controls exchange of metabolities, drugs, hormones, and nutrients the blod and brain in bidirectional manner, perfusing the veterbrate brain (2). Most compounds that do gain entry to brain cells involve a lipid-mediated transport process through the BBB. CNS targeted drugs, on the other hand, are designed to target the seven transmembrane-domain receptors of endothelial cells.

Dataset used in the develpment of CSBBB

CSBBB was developed with a dataset of 109 neutral compounds with a wide range of MW (16 to 632) as well as bveing chemical diverse. Small molecules such as N2, CH4 to known drugs (e.g., indinavir and analogs) were employed in building the CSBBB predictor. Our model is based on a multilinear regression using topological and proprietary descriptors. An external validation set of 28 compounds was employed to determine the accuracy of CSBBB in predicting a breach of the brain-barrier. It had an accuracy of 93% with external validation set.

(2) L. Hall, K. Rose, L.. Kier (2000) J. Chem. Inf. Comput. Sci. 42, 651

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