Correlation of blood-brain penetration using structural descriptors.
Experimental blood-brain partition coefficients (logBB) for a diverse set of 113 drug molecules are correlated with computed structural descriptors using CODESSA-PRO and ISIDA programs to give statistically significant QSAR models based respectively, on molecular and on fragment descriptors. The linear correlation CODESSA-PRO five-descriptor model has correlation coefficient R2=0.781 and standard deviation s2=0.123. The 'consensus model' of ISIDA gave R2=0.872 and s2=0.047. The developed models were successfully validated using the central nervous system activity data of an external test set of 40 drug molecules.
Katritzky
Alan R
AR
Center for Heterocyclic Compounds, Department of Chemistry, University of Florida, Gainesville, FL 32611, USA. katritzky@chem.ufl.edu
Kuanar
Minati
M
Slavov
Svetoslav
S
Dobchev
Dimitar A
DA
Fara
Dan C
DC
Karelson
Mati
M
Acree
William E
WE
Solov'ev
Vitaly P
VP
Varnek
Alexandre
A
D000465:Algorithms; D000818:Animals; D001812:Blood-Brain Barrier / Q000502:physiology*; D002491:Central Nervous System Agents / Q000737:chemistry* / Q000493:pharmacokinetics*; D015195:Drug Design; D006801:Humans; D008954:Models, Biological; D015233:Models, Statistical; D021281:Quantitative Structure-Activity Relationship; D012984:Software
D002491:Central Nervous System Agents