The physicochemical approach to drug design and discovery (QSAR)

The study of physicochemical parameters to correlate mathematically chemical structure with biological activity induced by sets of congeneric drugs is now generally referred to as QSAR (quantitative structure‐activity relationships). The ways in which the QSAR paradigm are developing are becoming more varied and complex. Many kinds of parameters are under study in many different groups; various types of mathematical models have been proposed and are being evaluated. Drug researchers are turning more to enzyme modulation to control various biological processes. It is the study of enzyme‐ligand reactions of enzymes whose x‐ray crystallographic structure is known that affords us the means for developing a deeper understanding of QSAR and, at the same time, enhancing our ability to make drugs more selective for various forms of a given enzyme. The union of x‐ray crystallography, moleculargraphics, and QSAR is one of the most exciting new areas of drug development. This report is an introduction to how QSAR is being used to gain insight into the interaction of drugs with macromolecules and macromolecular systems.