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.