IDENTIFYING NOVEL LEADS USING COMBINATORIAL LIBRARIES - ISSUES AND SUCCESSES

Chemically generated libraries of small, non-oligomeric compounds are being widely embraced by researchers in both industry and academia. Th ere has been a steady development of new chemistries and equipment app lied to library generation so it is now possible to synthesize almost any desired class of compound. However, there are still important issu es to consider that range from what specific types of compounds should be made to concerns such as sample resynthesis, structural confirmati on of the hit identified, and how to best integrate this technology in to a pharmaceutical drug discovery operation. This paper illustrates o ur approach to new lead discovery (individual, diverse, drug-like mole cules of known structural identity using a simple. spatially addressab le parallel synthesis approach to prepare Multiple Diverse as well as Universal Libraries) and describes some representative examples of che mistries we had developed within these approaches (preparation of bis- benzamide phenols, thiophenes, pyrrolidines, and highly substituted bi phenyls). Finally, the manuscript concludes by addressing some the pre sent concerns that still must be considered in this field.