Libraries lead identification

DOS seems mainly important for lead identification. Based on the lead structure, additional structural complexity can be introduced in a direct manner by generating focused libraries. For the synthesis of complex molecules, total synthesis as it exists today and the development of selective reactions that accompany, it remain of major importance. Even in case of the successful identification of advanced leads or drug candidates from DOS, an efficient total synthesis is always required in order to provide sufficient amounts of a limited set of derivatives for detailed medicinal chemistry studies up to clinical trials. 

General screening for lead identification screening a diverse library is a sensible approach when little or nothing is known about the target or possible lead compounds. 

Libraries targeted towards proteolytic enzymes, nonproteolytic enzymes, G-protein coupled receptors (GPCRs) and ion-channels have been very successful in lead identification. Libraries of hydroxamates (4), hydroxy ethyl-enes (5), boronic acids (6) and aketo sulfon-... 

However, identification of ion channel modulators by screening compound libraries enriched with ion channel privileged chemotypes offers rapid, efficient access to lead compounds. Flexible data-driven building and optimization of such an ion channel focused library will enable better and faster lead identification of ion channel modulators. 

The increasing information in biological and chemical space and its effective transformation into a knowledge-driven ion channel focused library may foster a paradigm shift in lead identification. 

---