History and Evolution of the Pharmacophore Concept in Computer-Aided Drug Design

With computer-aided drug design established as an integral part of the lead discovery and optimization process, pharmacophores have become a focal point for conceptualizing and understanding receptor-ligand interactions. In the structure-based design process, pharmacophores can be used to align molecules based on the three-dimensional arrangement of chemical features or to develop predictive models (e.g., 3D-QSAR) that correlate with the experimental activities of a given training set. Pharmacophores can be also used as search queries for retrieving potential leads from structural databases, for designing molecules with specific desired attributes, or as fingerprints for assessing similarity and diversity of molecules. This review article presents a historical perspective on the evolution and use of the pharmacophore concept in the pharmaceutical, biotechnology, and fragrances industry with published examples of how the technology has contributed and advanced the field.