P athological biochemical processes within a cell or an organism are usually caused by molecular interaction and recognition events. One major aim o f drug discovery projects
is to identify bioactive molecular structures that can be used to systematically interfere with such molecular processes and positively influence and eventually cure a disease. Both
significant biological activity and specificity o f action are important target functions for the molecular designer. In addition, one has to consider absorption, distribution, metabolic (ADME),
and potential toxic properties during the drug development process to ensure that the drug
candidate will have the desired Pharmacokinetic and pharmacodynamic properties. Usually the initial “hit”, i.e., a bioactive structure identified in a high-throughput screen (H TS) or any other biological test system, is turned into a “lead” structure. This often includes optimization/ minimization towards ADM E/Tox parameters. Further optimization is carried out as the com-
pounds enters the next phases o f drug discovery, namely lead optimization and development, nonclinical and finally clinical trials (Fig. 1.1). Only if all o f the required conditions are met can the molecule become a trade drug. The target function in drug design clearly is multi-
dimensional.2 Typically several rounds o f optimization must be performed to eventually obtain a clinical candidate.