THE CHALLENGE OF PREPARING AND TESTING COMBINATORIAL COMPOUND LIBRARIES IN THE FAST LANE, AT THE FRONT-END OF DRUG DEVELOPMENT

Combinatorial Compound Libraries (CCL) are at the front end of the dev elopment of new chemical entities. They are the result of a pragmatic, goal-oriented attitude, which emphasizes the discovery side of resear ch activities. The odds to bump into a discovery, however, are pushed to the extreme with rigorously planned rationales. The CCL field has i ts origin in peptide chemistry but is migrating into general organic c hemistry. The incentive is the coveted goal to be able to prepare larg e libraries of 'small molecules' Efforts are directed towards an expan sion of the repertoire of high yield reactions on solid phase, in orde r to readily access semi-rigid globular ligands. The CCL approach come s with its own strategies to provide a massive increase of compound ev aluations by taking full advantage of the integrated preparation proce ss with the option to control the physical format of compound ensemble s or to classify them into defined subpopulations. A noticeable impact on the drug discovery process is expected. The libraries' preparation and evaluation principles are briefly discussed in this essay.