Jm. Luco, Prediction of the brain-blood distribution of a large set of drugs from structurally derived descriptors using partial least-squares (PLS) modeling, J CHEM INF, 39(2), 1999, pp. 396-404
Citations number
42
Categorie Soggetti
Chemistry
Journal title
JOURNAL OF CHEMICAL INFORMATION AND COMPUTER SCIENCES
In this study, the multivariate partial least-squares projections to latent
structures (PLS) technique was used for modeling the brain-blood concentra
tion ratio (BB) of 61 structurally diverse compounds. The PLS model was bas
ed on molecular descriptors that can be calculated for any compound simply
from a knowledge of its molecular structure, and the model included several
topological and constitutional descriptors. The PLS analysis resulted in a
significant three-component model with the following statistics: r = 0.922
, Q = 0.867, s = 0.318, n = 58, and F = 102. The predictive ability of the
model was assessed by means of crossvalidation and also by using BE partiti
oning data, BBB permeability data, and 1 set of qualitative brain penetrati
on data, resulting in BE distribution data for 97 compounds. The results in
dicate that the PLS model developed is statistically sound and is sufficien
tly robust for predictive use. Taking into account the great ease of comput
ation and interpretation of the derived model, it may be of general utility
in predicting BE ratios for a very wide range of new drags.