INIFTA   05425
INSTITUTO DE INVESTIGACIONES FISICO-QUIMICAS TEORICAS Y APLICADAS
Unidad Ejecutora - UE
artículos
Título:
New QSPR Study for the Prediction of Aqueous Solubility of Drug-Like Compounds
Autor/es:
DUCHOWICZ, PABLO R.; TALEVI, A.; BRUNO-BLANCH, L. E.; CASTRO, E. A.
Revista:
BIOORGANIC & MEDICINAL CHEMISTRY.
Referencias:
Año: 2008 vol. 16 p. 7944 - 7955
ISSN:
0968-0896
Resumen:
Solubility has become one of the key physicochemical screens at early stages of the drug development
process. Solubility prediction through Quantitative StructureProperty Relationships (QSPR) modeling
is a growing area of modern pharmaceutical research, being compatible with both High Throughput
Screening technologies and limited compound availability characteristic of early stages of drug development.
We resort to the QSPR theory for analyzing the aqueous solubility exhibited by 145 diverse druglike
organic compounds (0.781 being the average Tanimoto distances between all possible pairs of
compounds in the training set). An accurate and generally applicable model is derived, consisting on a
linear regression equation that involves three DRAGON molecular descriptors selected from more than
a thousand available. Alternatively, we apply the linear QSPR to other 21 commonly employed validation
compounds, leading to solubility estimations that compare fairly well with the performance achieved by
previously reported Group Contribution Methods.