ABSTRACT
In a retrospective view, the last 30 years of drug research have witnessed a series of fundamental developments stimulated by the introduction of new methodologies [1-4]. Frequently enough, these new approaches or concepts have been announced as “a change in paradigm.” Undoubtedly, drug discovery has moved toward more rational concepts based on our increasing understanding of the fundamental principles of protein-ligand interactions [5,6]. Nowadays, serendipity, as a key element in drug research [7], plays a less important role, even though recent examples such as the discovery of sildenafil (Viagra
) might suggest the opposite [8]. Common to all these “revolutionary changes in paradigm” is the increased
knowledge about the spatial structure of the molecules involved and the improved expertise to manipulate and modify their properties in a well-planned fashion at the molecular level. However, in contrast to the expectations that these developments will provide a dramatic increase of new chemical entities reaching the market, a constant decrease of the number of launched products is observed [9]. Accordingly, the statement “a kingdom for an innovative and also tractable lead” is still essential for drug companies because novel leads remain the most important prerequisite for success and survival on the market.
