Pharmacophore features distributions in different classes of compounds.

A pharmacophore analysis approach was used to investigate and compare different classes of compounds relevant to the drug discovery process (specifically, drug molecules, compounds in high throughput screening libraries, combinatorial chemistry building blocks and nondrug molecules). The distributions for a set of pharmacophore features including hydrogen bond acceptors, hydrogen bond donors, negatively ionizable centers, positively ionizable centers and hydrophobic points, were generated and examined. Significant differences were observed between the pharmacophore profiles obtained for the drug molecules and those obtained for the high-throughput screening compounds, which appear to be closely related to the nondrug pharmacophore distribution. It is suggested that the analysis of pharmacophore profiles could be used as an additional tool for the property-based optimization of compound selection and library design processes, thus improving the odds of success in lead discovery projects.