Combinatorial early approaches

In the early days of combinatorial chemistry, there was an emphasis on building very large libraries however, these early approaches were disappointing, with libraries either failing to produce the hit rates expected or resulting in hits that had undesirable physicochemical properties to be considered as lead compounds [6]. More recently, the focus has shifted toward more rationally designed smaller libraries [7]. 

Although the preparation of the quite complex selector modules prior to the synthesis of the library represented a rather significant synthetic effort, this study showed clearly the potential of combinatorial chemistry in the early development stage of a chiral separation medium and demonstrated a novel approach to rapid screening that might be amenable to full automation in the future. 

An early example of a combinatorial approach to a reaction catalyzed by transition metal coordination compounds concerns phosphatase mimics, specifically in the hydrolysis of bis(/ -nitrophenyl)phosphate (1)—>(2) (Equation (l)) 29... 

Dimitrov S.D., N.C. Dimitrova, J.D. Walker, G.D. Veith, and O.G. Mekenyan (2003). Bioconcentration potential predictions based on molecular attributes— an early warning approach for chemicals found in humans, birds, fish and wildlife. QSAR and Combinatorial Science 22 58-68. 

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