Chemical approaches to the discovery of new drugs

The increased understanding of biological phenomena on a molecular level has made it possible to develop powerful approaches to the discovery of new drugs. Once a molecular hypothesis can be derived from the biochemistry, pharmacology, or physiology of the disease, a chemical strategy can be evolved to identify compounds that will serve as leads to new drugs. Several approaches are available and may be used individually or combined to solve a problem. Ideas can be generated from the structures of known biologically active compounds, from mechanistic studies of reactions catalysed by enzymes, or from molecular modelling of intermolecular interactions using advanced computer technology. All of these approaches require substantial inputs from organic (principally synthetic), physical, and theoretical chemists together with the biological contribution in the assay and evaluation of compounds. This article outlines some of the principles involved in the search for new drugs today discovery from the chemical point of view and illustrates the discussion with many examples of commercial drugs and compounds currently under development.