Entwurf Synthese und Evaluierung antiproliferativer Leitstrukturen und komplementärer Substanzbibliotheken Arzneimitteldesign Molecular modeling Organische Synthese in vitro Evaluierung Mikrowellensynthese in silico Wirkstoffdesign The relevance of modern approaches to fragment based lead discovery for the success and safety in drug development was demonstrated by the present work. In addition to the theoretical principles the practical application of molecular diversity with the help of complementary compound libraries could often directly illustrate the resulting benefits. Special interests were given to antiproliferative targets with particular emphasis on the inhibition of glutathione peroxidase. Furthermore in silico methods supported targeted syntheses. By optimizing the GPx 1 test system a reliable in vitro analysis could be established. In summary it can be stated that the successful development optimization and evaluation of multiple leads could be demonstrated for a variety of target proteins in tumor therapy by the help of the employed studies. Initially progress in the field of fragment based lead discovery via multipurpose screening libraries were reviewed and evaluated (publication 1). The presented approaches such as halogen bonding and sp3 wealth were put into practice within the following publications to a large extent. The synthesis of an extensive acylhydrazone library led to an increased inhibition against the bovine GPx 1 (publication 2). The combinatorial synthesis approach yielded a large number of closely related analogs which unfortunately provided little knowledge about SAR contrary to expectations. In addition the applied docking studies proved to be misleading since ...